The influenza vaccination is an annual vaccination using a vaccine specific for a given year to protect against the highly variable influenza virus. Each seasonal influenza vaccine contains antigens representing three (trivalent vaccine) or four (quadrivalent vaccine) influenza virus strains: one influenza type A subtype H1N1 virus strain, one influenza type A subtype H3N2 virus strain, and either one or two influenza type B virus strains. Influenza vaccines may be administered as an injection, also known as a flu shot, or as a nasal spray.
The U.S. Centers for Disease Control and Prevention recommend that everyone over the ages of 6 months should receive the seasonal influenza vaccine. Vaccination campaigns usually focus on people who are at high risk of serious complications if they catch the flu, such as the elderly and people living with chronic illness or those with weakened immune systems, as well as health care workers.
Overall most seasonal influenza vaccines showed efficacy or effectiveness, which was acceptable or high for laboratory-confirmed cases and of modest magnitude for clinically-confirmed cases. Influenza vaccine effectiveness can vary from year to year and among different age and risk groups. Despite somewhat limited research, the safety of flu vaccines is reassuring; there is no evidence that they can cause serious harm, and no reason for serious side effects to be a concern. The flu vaccine is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
- 1 Medical uses
- 2 Side effects
- 3 Cost-effectiveness
- 4 Vaccination recommendations
- 5 Manufacturing
- 6 History
- 7 Research
- 8 Veterinary use
- 9 References
- 10 External links
The WHO recommends annual vaccination for (in order of priority): nursing-home residents (the elderly or disabled), people with chronic medical conditions, elderly individuals and other groups such as pregnant women, health care workers, those with essential functions in society, as well as children from ages six months to two years.
According to the US CDC everyone who is at least 6 months of age should get a flu vaccine in 2013-2014. This recommendation has been in place since February 24, 2010 when CDC’s Advisory Committee on Immunization Practices (ACIP) voted for “universal” flu vaccination in the United States to expand protection against the flu to more people. Vaccination is especially important for some people:
People who are at high risk of developing serious complications (like pneumonia) if they get sick with the flu like people who have certain medical conditions including asthma, diabetes, and chronic lung disease, pregnant women, people younger than 5 years (and especially those younger than 2), and people 65 years and older. Also people with heart disease, diabetes mellitus, kidney disease, weakened immune system and morbidly obese people.
People who live with or care for others who are at high risk of developing serious complications as household contacts and caregivers of people with certain medical conditions including asthma, diabetes, and chronic lung disease, household contacts and caregivers of infants less than 6 months old, health care personnel.
An influenza epidemic emerges during flu season each winter. There are two flu seasons annually, corresponding to the occurrence of winter in the Northern and Southern Hemispheres (winter in one hemisphere is at the same time as summer in the other).
Although difficult to assess, these annual epidemics are thought to result in between three and five million cases of severe illness and between 250,000 and 500,000 deaths every year around the world. Tens of thousands of Americans die in a typical flu season, but there are notable variations from year to year. In 2010 the Centers for Disease Control and Prevention (CDC) in the United States changed the way it reports the 30-year estimates for deaths from influenza. They are reported as a range from a low of about 3,300 deaths to a high of 49,000 per year over the past 30 years.
The majority of influenza-caused deaths in the industrialized world occur in adults aged 65 and over. In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over age 65 is over ten times more likely to die an influenza-associated death than the 50–64 age group.
A review at the National Institute of Allergy and Infectious Diseases (NIAID) division of the National Institutes of Health (NIH) in 2008 concluded that "Seasonal influenza causes more than 200,000 hospitalizations and 41,000 deaths in the U.S. each year, and is the seventh leading cause of death in the U.S." The average total economic costs caused by the annual influenza outbreak in the U.S. have been estimated at over $80 billion.
The number of annual influenza-related hospitalizations is many times the number of deaths. "The high costs of hospitalizing young children for influenza creates a significant economic burden in the United States" The CDC has projected that a total of 38 million days of school were missed by American students due to the flu.
Efficacy and effectiveness
A vaccine is assessed by its efficacy; the extent to which it reduces risk of disease under controlled conditions (clinical trial), and its effectiveness, the observed reduction in risk after the vaccine is put into use (observational study). In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness, which is not always caused by influenza.
Overall most seasonal influenza vaccines showed statistically significant efficacy/effectiveness, which was acceptable or high for laboratory-confirmed cases and of modest magnitude for clinically-confirmed cases. Studies on the effectiveness of flu vaccines in the real world are uniquely difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses. However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains, and even a mis-matched vaccine can often provide cross-protection.
Nevertheless, multiple clinical trials and observational studies of both live and inactivated influenza vaccines against seasonal influenza have been performed and their results pooled and analyzed in several systematic reviews on different groups. Those examined the efficacy and effectiveness of vaccines against seasonal influenza in adults, children, the elderly and people at risk of complications.
In healthy adults a meta-analysis of cohort studies and clinical trials on the effectiveness of influenza vaccination trials conducted between 1967 and 2011, found the pooled efficacy of flu shots was 59%. So for healthy, working adults, influenza vaccines could provide moderate protection against virologically confirmed influenza, but such protection was greatly reduced or absent in some seasons. In adults the overall effectiveness of parenteral inactivated vaccine against influenza-like illness is limited, corresponding to a number needed to vaccinate (NNV) of 40. So 40 persons have to get a flu shot for one to avoid the "flu". The overall efficacy of inactivated vaccines in preventing confirmed influenza has a number needed to vaccinate (NNV) of 71. So 71 people have to get a flu shot to prevent one confirmed seasonal influenza. The difference between these two values depends on the different incidence of influenza-like illness and confirmed influenza among the study populations: 15.6% of unvaccinated participants versus 9.9% of vaccinated participants developed influenza-like illness symptoms, whilst only 2.4% and 1.1%, respectively, developed laboratory-confirmed influenza. There were no RCTs assessing vaccination in pregnant women found and the only evidence available came from observational studies with modest methodological quality. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates.
In adults live aerosol vaccines had an overall effectiveness corresponding to a number needed to vaccinate (NNV) of 46. The performance of one-dose or two-dose whole virion pandemic vaccines was higher, showing a number needed to vaccinate (NNV) of 16 against influenza-like illness and a NNV of 35 against influenza, while a limited impact on hospitalisation was found NNV 94.
In children older than two years influenza vaccines are efficacious in preventing influenza. In children under the age of two the data for live attenuated vaccine are extremely limited and vaccination with inactivated vaccines appeared to have no measurable benefit. In children under the age of six, 6 need to be vaccinated with live attenuated vaccine to prevent one case of influenza (efficacy). In children over the age of six, 28 need to be vaccinated with inactivated vaccine to prevent one case of influenza (efficacy) and 8 to prevent one case of influenza-like-illness (effectiveness). There was no proof of effect on secondary cases, lower respiratory tract disease, drug prescriptions, otitis media and socio-economic impact. Pooled efficacy of living attenuated vaccine was 83% in children aged 6 months to 7 years. No such trials met inclusion criteria for children aged 8–17 years. In an overarching meta-analysis for laboratory confirmed cases vaccine efficacy was around 60% for parenteral inactivated vaccines and around 68% for living attenuated vaccines, and for clinically confirmed cases respectively 38% and 33%.
In the elderly earlier individual cohort studies and a 2002 meta analyses from observational studies showed effectiveness. The meta analysis found reduced mortality from all causes by 50%. Several research groups have shown that some previous observational studies overestimated the mortality benefits of flu vaccination in the elderly. The studies were shown to be unreliable because of the "healthy user effect". Reasonably healthy elderly people were more likely to be vaccinated, and those in poorer health were less likely to be vaccinated and more likely to die for any reason. So systematic reviews found that there is still insufficient overall evidence to draw clear conclusions on the effectiveness of vaccination in the elderly, including a new high-dose flu vaccine for which available evidence indicates that the it produces a stronger immune response. One systematic review found that evidence for protection in adults aged 65 years or older was lacking, another found the available evidence was of poor quality and provided no guidance regarding the safety, efficacy or effectiveness of influenza vaccines for people aged 65 years or older. Moreover, it is well known that people over 65 years mount a weaker immune response to flu vaccines than younger adults do, as measured by antibody titers. The group most vulnerable to non-pandemic flu, the elderly, is also the least to benefit from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age.
Research is still lacking on the issues of the efficacy or effectiveness of influenza vaccination in people with serious medical conditions which place them at higher risk of complications. Data were insufficient for the effect from vaccination on prevention of coronary heart disease. A later meta analysis based on 6 clinical trials found, within one year in those at high risk of cardiovascular events, immunization might reduce the risk of major adverse cardiovascular events with a number needed to treat of 58 to prevent 1 major adverse cardiovascular event, with most effect in people with a recent acute coronary syndrome. A Dare critical appraisal found uncertainties surrounding the generally small and heterogeneous evidence base, and that the reliability of the findings remained uncertain and that they should be considered preliminary. In people with chronic obstructive pulmonary disease there was a decrease of exacerbations against placebo. There was not enough data to find an effect on mortality. In people with asthma (18 trials), or with bronchiectasis or cystic fibrosis disease effects are uncertain. In children with asthma in one trial there were no differences in the number of people experiencing an asthma attack (worsening of symptoms); however, people reported fewer asthma symptoms in weeks in which children had a positive test for influenza.
Vaccination is widely recommended for immunocompromised people as because they are vulnerable to severe or complicated influenza infection. A systematic review (209 studies, only 23 RCTs) about people with immunodepression as cancer, HIV and transplant patients found a high risk of bias in many studies. It showed a lower chance of preventing influenza-like illness and laboratory confirmed influenza by vaccinating immunocompromised patients compared to placebo or unvaccinated controls. It concluded that potential for bias and confounding and the presence of heterogeneity showed the evidence reviewed was generally weak, although the directions of effects were consistent. In people with haematological malignancies there was a lower risk of lower respiratory infections and hospitalisations, but the quality of evidence was low. In children treated with chemotherapy for cancer, in immunosuppressed adults with cancer and in people with HIV infections effects are uncertain.
Influenza vaccination has been shown highly effective in health care workers, with minimal adverse effects. In a study of forty matched nursing homes, staff influenza vaccination rates were 69.9% in the vaccination arm versus 31.8% in the control arm. The vaccinated staff experienced a 42% reduction in sick leave from work (P=.03). A review of eighteen studies likewise found a strong net benefit to health care workers. Of these eighteen health care worker studies, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of health care worker vaccination correlated with reduced patient deaths. Even though a 2010 Cochrane found no effect on laboratory-proven influenza, nor in pneumonia or deaths from pneumonia in people over 60 years old in long-term care facilities who were cared for by vaccinated health care workers from, vaccination of health care providers was nonetheless found to reduce patient influenza like infections and all-cause patient mortality .
Duration of protection
According to work published in 1973, 1983, and 2004, after vaccination against seasonal flu, antibody titres peak after typically two to four weeks. They decrease by about 50% over the next six months (the decrease is less for older adults), then remain stable for two to three years; protection without revaccination persists for at least three years for children and young adults.
The limited studies available do provide some evidence of a long-term immune effect. Immunity apparently does last a lifetime where it results from an actual flu infection, (as distinct from simply a vaccination). A 2008 study, published in Nature, found that 90 years after the 1918 pandemic, survivors had antibody-producing cells that produced antibodies with "remarkable power to block 1918 flu virus infection in mice, proving that, even nine decades after infection with this virus, survivors retain protection from it". As to long-term immunity from vaccination, a 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against a different swine flu outbreak in 1976, over 30 years before.
Injection versus nasal spray 
Flu vaccines are available either as
- TIV, QIV (injection of trivalent or quadrivalent, killed vaccine)
- LAIV, Q/LAIV (nasal spray of live attenuated influenza vaccine)
TIV (trivalent inactivated influenza vaccine) induces protection after injection (typically intramuscular, though subcutaneous and intradermal routes can also be protective) based on an immune response to the antigens present on the inactivated virus, while cold-adapted LAIV works by establishing infection in the nasal passages.
Annual seasonal flu vaccination provides some protection against flu viruses that the vaccine was not designed for, including novel viruses. The CDC made the following statement in relation to the 2007-2008 vaccine:
- ...[A]ntibodies made in response to vaccination with one strain of influenza viruses can provide protection against different, but related strains. A less than ideal match may result in reduced vaccine effectiveness against the variant viruses, but it still can provide enough protection to prevent or lessen illness severity and prevent flu-related complications. In addition, it is important to remember that the influenza vaccine contains three virus strains so the vaccine can also protect against the other two viruses. For these reasons, even during seasons when there is a less than ideal match, CDC continues to recommend influenza vaccination. This is particularly important for people at high risk for serious flu complications and their close contacts.
Overall data on vaccine harms are reassuring, but their value is diminished by inconsistent reporting. The side effects of vaccine are almost always minor, and are far less costly overall than the public and personal effects of unprotected exposure to the influenza virus, with its attendant risks of hospitalization or death.
Flu vaccination may lead to side effects such as runny nose and sore throat, which can last for up to several days. Egg allergy may also be a concern, since flu vaccines are typically made using eggs, however research into egg-allergy and influenza vaccination  has led some advisory groups to recommend vaccine delivery protocols for egg allergic persons.
The evidence for a causal association of influenza vaccine and Guillain-Barré is strongest for the swine influenza vaccine that was used in 1976-77. There was an estimated relative risk of Guillain-Barré of 7 - 8 after vaccination. Studies of influenza vaccines used in subsequent years, however, have found small or no increased risk of Guillain-Barré.  A US review found an incidence of about one case of Guillain-Barré per million influenza vaccinations. Getting infected by influenza itself increases the risk of developing Guillain-Barré syndrome to a much higher level than the highest level of suspected vaccine involvement (approx. 10 times higher by 2009 estimates).
Several studies in Finland, Sweden, Ireland, France, UK and Norway have identified an increased incidence of narcolepsy among recipients of the pandemic H1N1 influenza ASO3-adjuvanted vaccine in children and adolescents. Efforts to identify a mechanism for this suggest that narcolepsy is autoimmune, and that the H1N1 vaccine may mimic hypocretin, serving as a trigger.
Some injection-based flu vaccines intended for adults in the United States contain thiomersal (also known as thimerosal), a mercury-based preservative. Despite some controversy in the media, the World Health Organization's Global Advisory Committee on Vaccine Safety has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration.
The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings. In the elderly (aged over 65 years) the majority of published studies have found that vaccination is cost saving, with the cost savings associated with influenza vaccination (e.g. prevented health care visits) outweighing the cost of vaccination. In older adults (aged 50–64 years), several published studies have found that influenza vaccination is likely to be cost-effective, however the results of these studies were often found to be dependent on key assumptions used in the economic evaluations. The uncertainty in influenza cost-effectiveness models can partially be explained by the complexities involved in estimating the disease burden, as well as the seasonal variability in the circulating strains and the match of the vaccine. In healthy working adults (aged 18–49 years), a 2012 review found that vaccination was generally not cost-saving, with the suitability for funding being dependent on the willingness to pay to obtain the associated health benefits. In children, the majority of studies have found that influenza vaccination was cost-effective, however many of the studies included (indirect) productivity gains, which may not be given the same weight in all settings. Several studies have attempted to predict the cost-effectiveness of interventions (including prepandemic vaccination) to help protect against a future pandemic, however estimating the cost-effectiveness has been complicated by uncertainty as to the severity of a potential future pandemic and the efficacy of measures against it.
Various public health organizations, including the World Health Organization, have recommended that yearly influenza vaccination be routinely offered to patients at risk of complications of influenza and those individuals who live with or care for high-risk individuals, including:
- the elderly (UK recommendation is those aged 65 or above)
- patients with chronic lung diseases (asthma, COPD, etc.)
- patients with chronic heart diseases (congenital heart disease, chronic heart failure, ischaemic heart disease)
- patients with chronic liver diseases (including cirrhosis)
- patients with chronic renal diseases (such as the nephrotic syndrome)
- patients who are immunosuppressed (those with HIV or who are receiving drugs to suppress the immune system such as chemotherapy and long-term steroids) and their household contacts
- people who live together in large numbers in an environment where influenza can spread rapidly, such as prisons, nursing homes, schools, and dormitories.
- people who plan to attend or participate in a high profile important event with large numbers of people from various places (such as the Olympic Games, FIFA World Cup, and the World's Fair).
- people who are in the armed forces.
- healthcare workers (both to prevent sickness and to prevent spread to patients)
- pregnant women. However, a 2009 review concluded that there was insufficient evidence to recommend routine use of trivalent influenza vaccine during the first trimester of pregnancy. Influenza vaccination during flu season is part of recommendations for influenza vaccination of pregnant women in the United States.
- nursing-home residents (the elderly or disabled)
- people with chronic medical conditions
- elderly individuals
- other groups such as pregnant women, health care workers, those with essential functions in society, as well as children from 6 to 24 months.
According to the CDC, the live attenuated virus (which comes in the forum of the nasal spray in the US) should be avoided by:
- Children younger than 2 years
- Adults 50 years and older
- People with a history of severe allergic reaction to any component of the vaccine or to a previous dose of any influenza vaccine
- People with asthma
- Children or adolescents on long-term aspirin treatment.
- Children and adults who have chronic pulmonary, cardiovascular (except isolated hypertension), renal, hepatic, neurologic/neuromuscular, hematologic, or metabolic disorders
- Children and adults who have immunosuppression (including immunosuppression caused by medications or by HIV)
- Pregnant women
National advice on flu vaccination
In 2008, the National Advisory Committee on Immunization, the group that advises the Public Health Agency of Canada, recommended that everyone aged 2 to 64 years be encouraged to receive annual influenza vaccination, and that children between the age of six and 24 months, and their household contacts, should be considered a high priority for the flu vaccine. The NACI also recommends the flu vaccine for:
- People at high risk of influenza-related complications or hospitalization, including the morbidly obese, healthy pregnant women, children 6 to 59 months, the elderly, aboriginals, and people suffering from one of an itemized list of chronic health conditions
- People capable of transmitting influenza to those at high risk, including household contacts and healthcare workers
- People who provide essential community services
- Certain poultry workers
Within its blanket recommendation for general vaccination in the United States, the Centers for Disease Control and Prevention (CDC), who began recommending the influenza vaccine to health care workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their caregivers:
- Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications. In 2009, a new high-dose formulation of the standard influenza vaccine was approved. The Fluzone High Dose is specifically for people 65 and older; the difference is that it has four times the antigen dose of the standard Fluzone.
The U.S. government requires hospitals to report worker vaccination rates. Some U.S. states and hundreds of U.S. hospitals require health-care workers to either get vaccinations or wear masks during flu season. These requirements occasionally engender union lawsuits on narrow collective bargaining grounds, but proponents note that courts have generally endorsed forced vaccination laws affecting the general population during disease outbreaks.
Flu vaccine is usually grown by vaccine manufacturers in fertilized chicken eggs. In the Northern hemisphere, the manufacturing process begins following the announcement (typically in February) of the WHO recommended strains for the winter flu season. Three strains (representing an H1N1, an H3N2, and a B strain) of flu are selected and chicken eggs inoculated separately, these monovalent harvests are then combined to make the trivalent vaccine.
As of November 2007[update], both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union has also approved Optaflu, a vaccine produced by Novartis using vats of animal cells. This technique is expected to be more scalable and avoid problems with eggs, such as allergic reactions and incompatibility with strains that affect avians like chickens. Research continues into the idea of a "universal" influenza vaccine that would not require tailoring to a particular strain, but would be effective against a broad variety of influenza viruses. However, no vaccine candidates had been announced by Nov 2007.
A DNA-based vaccination, which is hoped to be even faster to manufacture, is as of 2011 in clinical trials, determining safety and efficacy.
In a 2007 report, the global capacity of approximately 826 million seasonal influenza vaccine doses (inactivated and live) was double the production of 413 million doses. In an aggressive scenario of producing pandemic influenza vaccines by 2013, only 2.8 billion courses could be produced in a six-month time frame. If all high- and upper-middle-income countries sought vaccines for their entire populations in a pandemic, nearly 2 billion courses would be required. If China pursued this goal as well, more than 3 billion courses would be required to serve these populations. Vaccine research and development is ongoing to identify novel vaccine approaches that could produce much greater quantities of vaccine at a price that is affordable to the global population.
Methods of vaccine generation that bypass the need for eggs include the construction of influenza virus-like particles (VLP). VLP resemble viruses, but there is no need for inactivation, as they do not include viral coding elements, but merely present antigens in a similar manner to a virion. Some methods of producing VLP include cultures of Spodoptera frugiperda Sf9 insect cells and plant-based vaccine production (e.g., production in Nicotiana benthamiana). There is evidence that some VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the hemagglutination-inhibition assay (HIA).
Each year, three strains are chosen for selection in that year's flu vaccination by the WHO Global Influenza Surveillance Network. The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. Starting with the 2012-2013 Northern Hemisphere influenza season (coincident with the approval of quadrivalent influenza vaccines), the WHO has also recommended a 2nd B-strain for use in quadrivalent vaccines. The World Health Organization coordinates the contents of the vaccine each year to contain the most likely strains of the virus to attack the next year.
- "The WHO Global Influenza Surveillance Network was established in 1952. The network comprises 4 WHO Collaborating Centres (WHO CCs) and 112 institutions in 83 countries, which are recognized by WHO as WHO National Influenza Centres (NICs). These NICs collect specimens in their country, perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO CCs for high level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year."
The Global Influenza Surveillance Network's selection of viruses for the vaccine manufacturing process is based on its best estimate of which strains will predominate the next year, amounting in the end to well-informed but fallible guesswork.
Formal WHO recommendations first issued in 1973; beginning 1999 there have been two recommendations per year, one for the northern hemisphere (N) and the other for the southern hemisphere (S).
Historical annual reformulations of the influenza vaccine are listed in a separate article. Recent[update] WHO seasonal influenza vaccine composition recommendations:
2014-2015 Northern Hemisphere influenza season
The composition of trivalent virus vaccines for use in the 2014-2015 Northern Hemisphere influenza season recommended by the World Health Organization on February 20, 2014 was:
- an A/California/7/2009 (H1N1)pdm09-like virus;
- an A/Texas/50/2012 (H3N2)-like virus
- B/Massachusetts/2/2012-like virus.
The WHO recommends that quadrivalent vaccines containing two influenza B viruses contain the above three viruses and a B/Brisbane/60/2008-like virus.
2014 Southern Hemisphere influenza season
The composition of virus vaccines for use in the 2014 Southern Hemisphere influenza season recommended by the World Health Organization September 26, 2013 was:
- an A/California/7/2009 (H1N1)pdm09-like virus;
- an A/Texas/50/2012 (H3N2)-like virus;
- a B/Massachusetts/2/2012-like virus.
It is recommended that quadrivalent vaccines containing two influenza B viruses contain the above three viruses and a B/Brisbane/60/2008-like virus.
The H1N1 strain used in these compositions is the same strain used in the 2009 flu pandemic vaccine, now known as A(H1N1)pdm09. As of December 2013[update], vaccine manufacturers estimate that 138-145 million doses of flu vaccine to be produced during the 2013-2014 Northern Hemisphere influenza season.
2014 Vaccine Products
Every year, multiple manufacturers produce and market the influenza vaccination. Below is a list of the common vaccinations available:
•Flulaval - Distributed by GlaxoSmithKline and manufactured in Quebec City, QC, Canada.
•Afluria - Distributed by Merck and manufactured in Parkville, Victoria Australia.
•Fluarix - Distributed by GlaxoSmithKline and manufactured in Dresden, Germany.
•Fluvirin -Distributed by Novartis and manufactured in Liverpool, UK
•Fluzone - Distributed by Sanofi Pasteur and manufactured in Swiftwater, PA 18370 USA.
Vaccines are used in both humans and nonhumans. Human vaccine is meant unless specifically identified as a veterinary, poultry or livestock vaccine.
The first influenza pandemic was recorded in 1580. However, the etiological cause of influenza, the orthomyxoviridae was discovered by the Medical Research Council (MRC) of the United Kingdom in 1933.
|Name of pandemic||Date||Deaths||Case fatality rate||Subtype involved||Pandemic severity index|
|1889–1890 flu pandemic
(Asiatic or Russian Flu)
|1889–1890||1 million||0.15%||possibly H3N8
|1918 flu pandemic
|1918–1920||20 to 100 million||2%||H1N1||5|
|Asian Flu||1957–1958||1 to 1.5 million||0.13%||H2N2||2|
|Hong Kong Flu||1968–1969||0.75 to 1 million||<0.1%||H3N2||2|
|Russian flu||1977–1978||no accurate count||N/A||H1N1||N/A|
|2009 flu pandemic||2009–2010||18,000||0.03%||H1N1||NA|
Origins and development
In the world wide Spanish flu pandemic of 1918, "Physicians tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and sera (chiefly against what we now call Hemophilus influenzae—a name derived from the fact that it was originally considered the etiological agent—and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."
In 1931, viral growth in embryonated hens' eggs was reported by Ernest William Goodpasture and colleagues at Vanderbilt University. The work was extended to growth of influenza virus by several workers, including Thomas Francis, Jonas Salk, Wilson Smith and Macfarlane Burnet, leading to the first experimental influenza vaccines. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used in the Second World War. Hen's eggs continued to be used to produce virus used in influenza vaccines, but manufacturers made improvements in the purity of the virus by developing improved processes to remove egg proteins and to reduce systemic reactivity of the vaccine. Recently, the US FDA has approved influenza vaccines made by growing virus in cell cultures and influenza vaccines made from recombinant proteins have been approved, with plant-based influenza vaccines being tested in clinical trials.
According to the CDC: "Influenza vaccination is the primary method for preventing influenza and its severe complications. [...] Vaccination is associated with reductions in influenza-related respiratory illness and physician visits among all age groups, hospitalization and death among persons at high risk, otitis media among children, and work absenteeism among adults. Although influenza vaccination levels increased substantially during the 1990s, further improvements in vaccine coverage levels are needed".
The egg-based technology (still in use as of 2005) for producing influenza vaccine was created in the 1950s. In the U.S. swine flu scare of 1976, President Gerald Ford was confronted with a potential swine flu pandemic. The vaccination program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base a number of soldiers fell severely ill, but only one died. The program was canceled, after about 24% of the population had received vaccinations. An excess in deaths of twenty-five over normal annual levels as well as 400 excess hospitalizations, both from Guillain-Barré syndrome, were estimated to have occurred from the vaccination program itself, illustrating that vaccine itself is not free of risks. The result has been cited to stoke lingering doubts about vaccination. In the end, however, even the maligned 1976 vaccine may have saved lives. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976.
Influenza research includes molecular virology, molecular evolution, pathogenesis, host immune responses, genomics, and epidemiology. These help in developing influenza countermeasures such as vaccines, therapies and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. The Influenza Genome Sequencing Project is creating a library of influenza sequences that will help us understand what makes one strain more lethal than another, what genetic determinants most affect immunogenicity, and how the virus evolves over time. Solutions to limitations in current[when?] vaccine methods are being researched.
According to VaccineNewsDaily, a recent study published in Vaccines found that by providing a school-located vaccination clinic, flu vaccination rates among children increased 13.2 percent when compared to children in schools without vaccination clinics. The vaccine can be lifesaving for children and less costly than a doctor's office visit.
The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based) technology and recombinant technologies (proteins and virus-like particles). As of July 2009, more than 70 known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the US Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus (the 2009 pandemic strain), and expected the initial vaccine lots to be available within the following month. A quadrivalent flu vaccine administered by nasal mist was approved by the U.S. Food and Drug Administration (FDA) in March 2012. Fluarix Quadrivalent was approved by the FDA in December 2012.
Prospects for universal flu vaccines
Many groups worldwide are pursuing development of a universal flu vaccine that does not require modification each year. Companies pursuing the vaccine as of 2009 and 2010 include BiondVax, Theraclone, Dynavax Technologies Corporation, VaxInnate, Crucell NV, Inovio Pharmaceuticals, and Immune Targeting Systems (ITS)
In 2008, Acambis announced work on a universal flu vaccine (ACAM-FLU-ATM) based on the less variable M2 protein component of the flu virus shell. The vaccine was tested in a human trial in the United States, where it was reported in 2008 to have developed antibodies against flu virus in 90% of individuals; further human trials were planned. See also H5N1 vaccines.
In 2010, the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. NIH announced a breakthrough; the effort targets the stem, which mutates less often than the head of the virus.
In July 2011, researchers created an antibody, which targets a protein found on the surface of all influenza A viruses called haemagglutinin. F16 is the only known antibody that binds (its neutralizing activity is controversial) to all 16 subtypes of the influenza A virus hemagglutinin and might be the lynchpin for a universal influenza vaccine. The subdomain of the hemagglutinin that is targeted by FI6, namely the stalk domain, was actually successfully used earlier as universal influenza virus vaccine by Peter Palese's research group at Mount Sinai School of Medicine.
Chimeric hemagglutinin constructs that contain exotic head domains with conserved stalk regions have also been proposed and created to elicit the generation of stalk-specific antibodies. Studies in mice that have been repeatedly immunized with such constructs showed robust protection and broad-based immunity against several strains of viruses. A proposed universal flu vaccination strategy includes a priming vaccine followed by two booster vaccines.
Other vaccines are polypeptide based.
Some universal flu vaccines have started early stage clinical trials.
- BiondVax are targeting the less variable stalk of the haemagglutinin molecule with Multimeric-001. This is aimed at type A (inc H1N1) and Type B influenza and has started a phase IIa study.
- Dynavax have developed a vaccine N8295 based on two highly conserved antigens NP and M2e and their TLR9 agonist, and started clinical trials in June 2010.
- ITS's fp01 includes 6 peptide antigens to highly conserved segments of the PA, PB1, PB2, NP & M1 proteins, and has started phase I trials.
Based on the results of animal studies, a universal flu vaccine may use a two-step vaccination strategy — priming with a DNA-based HA vaccine followed by a second dose with an inactivated, attenuated, or adenovirus-vector–based vaccine.
On February 13, 2013, U.S. Food and Drug Administration (FDA) Chief Scientist Jesse Goodman predicted that a universal flu vaccine was still 5 to 10 years away. When asked about the prospects of a universal flu vaccine in a hearing before House Energy and Commerce Subcommittee on Oversight and Investigations, Goodman replied "Nature is very tricky and as this is a very crafty virus, so I'd be very hesitant to predict... I think the earliest we'd begin to see something with clinical benefit might be 5 to 10 years."
"Vaccination in the veterinary world pursues four goals: (i) protection from clinical disease, (ii) protection from infection with virulent virus, (iii) protection from virus excretion, and (iv) serological differentiation of infected from vaccinated animals (so-called DIVA principle). In the field of influenza vaccination, neither commercially available nor experimentally tested vaccines have been shown so far to fulfill all of these requirements."
Horses with horse flu can run a fever, have a dry hacking cough, have a runny nose, and become depressed and reluctant to eat or drink for several days but usually recover in two to three weeks. "Vaccination schedules generally require a primary course of 2 doses, 3–6 weeks apart, followed by boosters at 6–12 month intervals. It is generally recognized that in many cases such schedules may not maintain protective levels of antibody and more frequent administration is advised in high-risk situations."
It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the International Federation for Equestrian Sports (FEI) requires vaccination every six months.
Poultry vaccines for bird flu are made on the cheap and are not filtered and purified like human vaccines to remove bits of bacteria or other viruses. They usually contain whole virus, not just hemagglutinin as in most human flu vaccines. Purification to standards needed for humans is far more expensive than the original creation of the unpurified vaccine from eggs. There is no market for veterinary vaccines that are that expensive. Another difference between human and poultry vaccines is that poultry vaccines are adjuvated with mineral oil, which induces a strong immune reaction but can cause inflammation and abscesses. "Chicken vaccinators who have accidentally jabbed themselves have developed painful swollen fingers or even lost thumbs, doctors said. Effectiveness may also be limited. Chicken vaccines are often only vaguely similar to circulating flu strains — some contain an H5N2 strain isolated in Mexico years ago. 'With a chicken, if you use a vaccine that's only 85 percent related, you'll get protection,' Dr. Cardona said. 'In humans, you can get a single point mutation, and a vaccine that's 99.99 percent related won't protect you.' And they are weaker [than human vaccines]. 'Chickens are smaller and you only need to protect them for six weeks, because that's how long they live till you eat them,' said Dr. John J. Treanor, a vaccine expert at the University of Rochester. Human seasonal flu vaccines contain about 45 micrograms of antigen, while an experimental A(H5N1) vaccine contains 180. Chicken vaccines may contain less than 1 microgram. 'You have to be careful about extrapolating data from poultry to humans,' warned Dr. David E. Swayne, director of the agriculture department's Southeast Poultry Research Laboratory. 'Birds are more closely related to dinosaurs.'"
Researchers, led by Nicholas Savill of the University of Edinburgh in Scotland, used mathematical models to simulate the spread of H5N1 and concluded that "at least 95 percent of birds need to be protected to prevent the virus spreading silently. In practice, it is difficult to protect more than 90 percent of a flock; protection levels achieved by a vaccine are usually much lower than this." The Food and Agriculture Organization of the United Nations has issued recommendations on the prevention and control of avian influenza in poultry, including the use of vaccination.
A filtered and purified Influenza A vaccine for humans is being developed[when?] and many countries have recommended it be stockpiled so if an Avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu.
Swine influenza has been recognized as a greater problem since the outbreak in 1976. Evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine origin flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection and custom (autogenous) vaccines made from the specific viruses isolated are created and used in the more difficult cases. SoIV vaccine manufacture Novartis paints this picture: "A strain of swine origin influenza virus (SoIV) called H3N2, first identified in the US in 1998, has brought exasperating production losses to swine producers. Abortion storms are a common sign. Sows go off feed for two or three days and run a fever up to 106°F. Mortality in a naïve herd can run as high as 15%."
In 2004, Influenza A virus subtype H3N8 was discovered to cause canine influenza. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine is now available.
- Couch, RB (2008). "Seasonal Inactivated Influenza Virus Vaccines". Vaccine. 26 Suppl 4 (Suppl 4): D5–9. doi:10.1016/j.vaccine.2008.05.076. PMC 2643340. PMID 18602728.
- "Key Facts About Seasonal Flu Vaccine"
- [No authors listed] (2011-09-09). "Who Should Get Vaccinated Against Influenza". U.S. Centers for Disease Control and Prevention. Retrieved 2013-04-07.
- World Health Organization. Seasonal Influenza
- Manzoli L, Ioannidis JP, Flacco ME, De Vito C, Villari P (July 2012). "Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly: a critical review and re-analysis of 15 meta-analyses". Hum Vaccin Immunother 8 (7): 851–62. doi:10.4161/hv.19917. PMC 3495721. PMID 22777099.
- "Key Facts About Seasonal Flu Vaccine March 6, 2014". CDC. Retrieved 24 April 2014.
- "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
- "InfluenzavVaccine use". WHO. Retrieved 25 April 2014.
- "Key Facts About Seasonal Flu Vaccine March 6, 2014". CDC.
- WHO Influenza Overview
- "Estimates of deaths associated with seasonal influenza – United States, 1976-2007". MMWR Morb. Mortal. Wkly. Rep. (Centers for Disease Control and Prevention (CDC)) 59 (33): 1057–62. August 2010. PMID 20798667.
- Julie Steenhuysen (August 26, 2010). "CDC backs away from decades-old flu death estimate". Reuters. Retrieved 2010-09-13.
- Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K (2003). "Mortality associated with influenza and respiratory syncytial virus in the United States". The Journal of the American Medical Association 289 (2): 179–186. doi:10.1001/jama.289.2.179. PMID 12517228.
- Beigel, J. H. (2008). "Influenza". Critical Care Medicine 36 (9): 2660–2666. doi:10.1097/CCM.0b013e318180b039. PMC 3431208. PMID 18679129.
- WHO Influenza Overview http://www.who.int/mediacentre/factsheets/2003/fs211/en/
- "In the United States of America, for example, recent estimates put the cost of influenza epidemics to the economy at US$ 71-167 billion per year."
- Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. (June 2007). "The annual impact of seasonal influenza in the US: measuring disease burden and costs". Vaccine 25 (27): 5086–96. doi:10.1016/j.vaccine.2007.03.046. PMID 17544181. Estimates that in the United States, annual inﬂuenza epidemics result in approximately 600,000 life-years lost, 3 million hospitalized days, and 30 million outpatient visits, resulting in direct medical costs of $10 billion annually. Lost earnings due to illness and loss of life added over $15 billion in direct costs annually and the average of all direct and indirect economic burdens of annual inﬂuenza epidemics (funeral expenses, lost productivity, etc.) amounts to over $80 billion.
- Huge flu vaccine trial to be held. March 31, 2008 :"Professor Robert Booy, of the National Centre for Immunisation Research and Surveillance at Westmead in Sydney, said influenza put 15,000 Australians in hospital each year."
- "About 1,500 deaths annually are attributed to the virus and it costs our country millions of dollars annually in lost productivity, Professor Robert Booy said.
- "Young Children Hospitalized for Flu Associated With Higher Costs and Higher Risk Illness" (Press release). Cincinnati Children's Hospital Medical Center. May 4, 2008. "After analyzing data in three U.S. cities over the course of three flu seasons (2003-2006), the researchers found that 90 percent of the highest-cost hospitalizations for children were linked to influenza, or flu with a co-infection of the respiratory tract"
- CDC (November 17, 2011). "Adolescent School Health".
- Fedson DS (1998). "Measuring protection: efficacy versus effectiveness". Dev Biol Stand 95: 195–201. PMID 9855432.
- Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E (2010). "Vaccines for preventing influenza in healthy adults". Cochrane Database Syst Rev (7): CD001269. doi:10.1002/14651858.CD001269.pub4. PMID 20614424.
- Manzoli, Lamberto; Ioannidis, John P.A.; Flacco, Maria Elena; De Vito, Corrado; Villari, Paolo (1 July 2012). "Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly: A critical review and re-analysis of 15 meta-analyses". Human vaccines & immunotherapeutics 8 (7): 851–862. doi:10.4161/hv.19917.
- Jefferson, T. (October 2006). "Influenza vaccination: policy versus evidence". BMJ 333 (7574): 912–5. doi:10.1136/bmj.38995.531701.80. PMC 1626345. PMID 17068038.
- CDC - Influenza (Flu) | Q & A: 2007-08 Flu Season
- CDC - seasonal flu
- Jefferson, T; Di Pietrantonj, C; Rivetti, A; Bawazeer, GA; Al-Ansary, LA; Ferroni, E (Mar 13, 2014). "Vaccines for preventing influenza in healthy adults.". The Cochrane database of systematic reviews 3: CD001269. PMID 24623315.
- Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E (2012). "Vaccines for preventing influenza in healthy children". Cochrane Database Syst Rev 8: CD004879. doi:10.1002/14651858.CD004879.pub4. PMID 22895945.
- Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE (2010). "Vaccines for preventing influenza in the elderly". Cochrane Database Syst Rev (2): CD004876. doi:10.1002/14651858.CD004876.pub3. PMID 20166072.
- Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, Demicheli V (2005). "Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review". Lancet 366 (9492): 1165–74. doi:10.1016/S0140-6736(05)67339-4. PMID 16198765.
- Osterholm, MT; Kelley, NS; Sommer, A; Belongia, EA (2012). "Efficacy and effectiveness of influenza vaccines: A systematic review and meta-analysis". The Lancet Infectious Diseases 12 (1): 36–44. doi:10.1016/S1473-3099(11)70295-X. PMID 22032844. Also discussed in "Efficacy and Effectiveness of Influenza Vaccines: A Systematic Review and Meta-analysis". JournalistsResource.org, retrieved February 2, 2012
- Nichol, K.L.; Nordin, J.D.; Nelson, D.B.; Mullooly, J.D.; Hak, E. (2007). "Effectiveness of Influenza Vaccine in the community-dwelling elderly". The New England Journal of Medicine 357 (14): 1373–1381. doi:10.1056/NEJMoa070844. PMID 17914038.
- Vu, T.; Farish, S.; Jenkins, M.; Kelly, H. (2002). "A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community". Vaccine 20 (13–14): 1831–1836. doi:10.1016/S0264-410X(02)00041-5. PMID 11906772.
- Nordin, J.; Mullooly, J.; Poblete, S.; Strikas, R.; Petrucci, R.; Wei, F.; Rush, B; Safirstein, B et al. (2001). "Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: Data from 3 health plans". The Journal of Infectious Diseases 184 (6): 665–670. doi:10.1086/323085. PMID 11517426.
- Moyer, Melinda (Oct 18, 2012). "Flu Shots May Not Protect the Elderly or the Very Young". Scientific American.flu-shots-may-not-protect-the-elderly-or-the-very-young/
- Simonsen L, Viboud C, Taylor RJ, Miller MA, Jackson L (October 2009). "Influenza vaccination and mortality benefits: new insights, new opportunities". Vaccine 27 (45): 6300–4. doi:10.1016/j.vaccine.2009.07.008. PMID 19840664.
- "CDC - Seasonal Influenza (Flu) - Q & A: Fluzone High-Dose Seasonal Influenza Vaccine". Cdc.gov. August 13, 2013. Retrieved October 17, 2013.
- Roos, Robert. "Strict meta-analysis raises questions about flu vaccine efficacy Oct 25, 2011". CIDRAP. Retrieved 26 April 2014.
- Simonsen, L.; Taylor, R.J.; Viboud, C.; Miller, M.A.; Jackson, L.A. (2007). "Mortality benefits of influenza vaccination in elderly people: An ongoing controversy". The Lancet Infectious Diseases 7 (10): 658–666. doi:10.1016/S1473-3099(07)70236-0. PMID 17897608.
- Keller, T; Weeda, VB; van Dongen, CJ; Levi, M (Jul 16, 2008). "Influenza vaccines for preventing coronary heart disease.". The Cochrane database of systematic reviews (3): CD005050. PMID 18646119.
- Udell, JA.; Zawi, R.; Bhatt, DL.; Keshtkar-Jahromi, M.; Gaughran, F.; Phrommintikul, A.; Ciszewski, A.; Vakili, H. et al. (Oct 2013). "Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis.". JAMA 310 (16): 1711–20. doi:10.1001/jama.2013.279206. PMID 24150467. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0060456/
- Poole, PJ; Chacko, E; Wood-Baker, RW; Cates, CJ (Jan 25, 2006). "Influenza vaccine for patients with chronic obstructive pulmonary disease.". The Cochrane database of systematic reviews (1): CD002733. PMID 16437444.
- Cates, CJ; Rowe, BH (Feb 28, 2013). "Vaccines for preventing influenza in people with asthma.". The Cochrane database of systematic reviews 2: CD000364. PMID 23450529.
- Chang, CC; Morris, PS; Chang, AB (Jul 18, 2007). "Influenza vaccine for children and adults with bronchiectasis.". The Cochrane database of systematic reviews (3): CD006218. PMID 17636836.
- Dharmaraj, P; Smyth, RL (Oct 7, 2009). "Vaccines for preventing influenza in people with cystic fibrosis.". The Cochrane database of systematic reviews (4): CD001753. PMID 19821281.
- Cates, C.J. "Vaccines for preventing flu in people with asthma". Cochrane summaries. Retrieved 28 April 2014.
- Beck, Charles R.; McKenzie, Bruce C.; Hashim, Ahmed B.; Harris, Rebecca C.; Zanuzdana, Arina; Agboado, Gabriel; Orton, Elizabeth; Béchard-Evans, Laura; Morgan, Gemma; Stevenson, Charlotte; Weston, Rachel; Mukaigawara, Mitsuru; Enstone, Joanne; Augustine, Glenda; Butt, Mobasher; Kim, Sophie; Puleston, Richard; Dabke, Girija; Howard, Robert; O'Boyle, Julie; O'Brien, Mary; Ahyow, Lauren; Denness, Helene; Farmer, Siobhan; Figureroa, Jose; Fisher, Paul; Greaves, Felix; Haroon, Munib; Haroon, Sophie; Hird, Caroline; Isba, Rachel; Ishola, David A.; Kerac, Marko; Parish, Vivienne; Roberts, Jonathan; Rosser, Julia; Theaker, Sarah; Wallace, Dean; Wigglesworth, Neil; Lingard, Liz; Vinogradova, Yana; Horiuchi, Hiroshi; Peñalver, Javier; Nguyen-Van-Tam, Jonathan S.; Cowling, Benjamin J. (22 December 2011). "Influenza Vaccination for Immunocompromised Patients: Systematic Review and Meta-Analysis from a Public Health Policy Perspective". PLoS ONE 6 (12): e29249. doi:10.1371/journal.pone.0029249.
- Cheuk, DK; Chiang, AK; Lee, TL; Chan, GC; Ha, SY (Mar 16, 2011). "Vaccines for prophylaxis of viral infections in patients with hematological malignancies.". The Cochrane database of systematic reviews (3): CD006505. PMID 21412895.
- Goossen, GM; Kremer, LC; van de Wetering, MD (Aug 1, 2013). "Influenza vaccination in children being treated with chemotherapy for cancer.". The Cochrane database of systematic reviews 8: CD006484. PMID 23904194.
- Eliakim-Raz, N; Vinograd, I; Zalmanovici Trestioreanu, A; Leibovici, L; Paul, M (Oct 29, 2013). "Influenza vaccines in immunosuppressed adults with cancer.". The Cochrane database of systematic reviews 10: CD008983. doi:10.1002/14651858.cd008983.pub2. PMID 24166741.
- Anema, A; Mills, E; Montaner, J; Brownstein, JS; Cooper, C (Jan 2008). "Efficacy of influenza vaccination in HIV-positive patients: a systematic review and meta-analysis.". HIV medicine 9 (1): 57–61. doi:10.1111/j.1468-1293.2008.00515.x. PMID 18199173.
- Lemaitre, M.; Meret, T.; Rothan-Tondeur, M.; Belmin, J.; Lejonc, J. L.; Luquel, L.; Piette, F.; Salom, M.; Verny, M.; Vetel, J. M.; Veyssier, P.; Carrat, F. (September 2009). "Effect of influenza vaccination of nursing home staff on mortality of residents: a cluster-randomized trial". Journal of the American Geriatrics Society 57 (9): 1580–1586. doi:10.1111/j.1532-5415.2009.02402.x. PMID 19682118.
- Burls, A.; Jordan, R.; Barton, P.; Olowokure, B.; Wake, B.; Albon, E.; Hawker, J. (2006). "Vaccinating healthcare workers against influenza to protect the vulnerable—Is it a good use of healthcare resources?A systematic review of the evidence and an economic evaluation". Vaccine 24 (19): 4212–4221. doi:10.1016/j.vaccine.2005.12.043. PMID 16546308.
- Thomas RE, Jefferson T, Lasserson TJ (2010). "Influenza vaccination for healthcare workers who work with the elderly". Cochrane Database Syst Rev (2): CD005187. doi:10.1002/14651858.CD005187.pub3. PMID 20166073.
- Duration of Serum Antibody Response to Seasonal Influenza Vaccines: Summary, presentation citing references
- e! Science News,Survivors of 1918 flu pandemic protected with a lifetime immunity to virus
- McCullers JA, Van De Velde LA, Allison KJ, Branum KC, Webby RJ, Flynn PM (June 2010). "Vaccinees against the 1976 "swine flu" have enhanced neutralization responses to the 2009 novel H1N1 influenza virus". Clin. Infect. Dis. 50 (11): 1487–92. doi:10.1086/652441. PMC 2946351. PMID 20415539.
- Plotkin & Mortimer (1988). Vaccines. Philadelphia: W.B. Saunders Company. ISBN 0-7216-1946-0.
- Product Monograph: Flumist, Astrazeneca Canada Inc., 2011
- immunize.org article Summary of Recommendations for Adult Immunization, which is linked from CDC website CDC
- "The Nasal-Spray Flu Vaccine (Live Attenuated Influenza Vaccine [LAIV])" Centers for Disease Control and Prevention (CDC)
- Xie H, Jing X, Li X, et al. (2011). "Immunogenicity and cross-reactivity of 2009-2010 inactivated seasonal influenza vaccine in US adults and elderly". PLoS ONE 6 (1): e16650. Bibcode:2011PLoSO...616650X. doi:10.1371/journal.pone.0016650. PMC 3031605. PMID 21304946.
- CDC - Inactivated Influenza Vaccine 2007-2008 - What You Need To Know
- Flu - LAIV
- Gagnon, R; Primeau MN; Des Roches A; Lemire C; Kagan R; Carr S; Ouakki M; Benoît M; De Serres G (August 2010). "Safe vaccination of patients with egg allergy with an adjuvanted pandemic H1N1 vaccine.". The Journal of Allergy and Clinical Immunology 126 (2): 317–323. doi:10.1016/j.jaci.2010.05.037. PMID 20579720.
- National Advisory Committee on Immunization (August 2012). "Statement on Seasonal Influenza Vaccine for 2012-2013". Canadian Communicable Disease Report 38. Retrieved 18 July 2013.
- Haber P, Sejvar J, Mikaeloff Y, DeStefano F (2009). "Vaccines and Guillain-Barré syndrome". Drug Safety 32 (4): 309–23. doi:10.2165/00002018-200932040-00005. PMID 19388722.
- Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P (March 2009). "Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring". Vaccine 27 (15): 2114–2120. doi:10.1016/j.vaccine.2009.01.125. PMID 19356614.
- Stowe J, Andrews N, Wise L, Miller E (February 2009). "Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenzalike illness using the United Kingdom General Practice Research Database". Am. J. Epidemiol. 169 (3): 382–8. doi:10.1093/aje/kwn310. PMID 19033158.
- Sivadon-Tardy V; Orlikowski, David; Porcher, Raphaël; Sharshar, Tarek; Durand, Marie‐Christine; Enouf, Vincent; Rozenberg, Flore; Caudie, Christiane; Annane, Djillali; Van Der Werf, Sylvie; Lebon, Pierre; Raphaël, Jean‐Claude; Gaillard, Jean‐Louis; Gault, Elyanne (January 2009). "Guillain-Barré syndrome and influenza virus infection". Clin. Infect. Dis. 48 (1): 48–56. doi:10.1086/594124. PMID 19025491.
- TECHNICAL REPORT: Narcolepsy in association with pandemic influenza vaccination. Stockholm, Sweden: European Centre for Disease Prevention and Contro. 2012. ISBN 978-92-9193-388-4.
- Yong, Ed (18 December 2013). "Narcolepsy confirmed as autoimmune disease". Nature. doi:10.1038/nature.2013.14413.
- Offit PA (September 2007). "Thimerosal and vaccines—a cautionary tale". N Engl J Med (PDF ) 357 (13): 1278–9. doi:10.1056/NEJMp078187. PMID 17898096.
- Global Advisory Committee on Vaccine Safety (2006-07-14). "Thiomersal and vaccines". World Health Organization. Retrieved 2007-11-20.
- Jit, Mark; Newall, Anthony T.; Beutels, Philippe (1 April 2013). "Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies". Human vaccines & immunotherapeutics 9 (4): 834–840. doi:10.4161/hv.23637.
- Postma, M.J; Baltussen, R.P.M.; Palache, A.M; Wilschut, J.C. (2006). "Further evidence for favorable cost-effectiveness of elderly influenza vaccination". Expert Review of Pharmacoeconomics and Outcomes Research 6 (2). doi:10.1586/14737126.96.36.199. PMID 20528557.
- Newall, AT; Kelly, H; Harsley, S; Scuffham, PA (2009). "Cost Effectiveness of Influenza Vaccination in Older Adults". PharmacoEconomics 27 (6): 439–50. doi:10.2165/00019053-200927060-00001. PMID 19640008.
- Newall, AT; Viboud, C; Wood, JG (2009). "Influenza-attributable mortality in Australians aged more than 50 years: A comparison of different modelling approaches". Epidemiology and Infection 138 (6): 836–42. doi:10.1017/S095026880999118X. PMID 19941685.
- Newall, Anthony T.; Dehollain, Juan Pablo; Creighton, Prudence; Beutels, Philippe; Wood, James G. (4 May 2013). "Understanding the Cost-Effectiveness of Influenza Vaccination in Children: Methodological Choices and Seasonal Variability". PharmacoEconomics 31 (8): 693–702. doi:10.1007/s40273-013-0060-7.
- Newall, A.T.; Scuffham, P.A (2011). "Uncertainty and variability in influenza cost-effectiveness models". Australian and New Zealand Journal of Public Health 35 (6). doi:10.1111/j.1753-6405.2011.00788.x. PMID 22151168.
- Gatwood, J; Meltzer, MI; Messonnier, M; Ortega-Sanchez, IR; Balkrishnan, R; Prosser, LA (2012). "Seasonal Influenza Vaccination of Healthy Working-Age Adults". Drugs 72 (1): 35–48. doi:10.2165/11597310-000000000-00000. PMID 22191794.
- Newall, Anthony T.; Jit, Mark; Beutels, Philippe (August 1, 2012). "Economic Evaluations of Childhood Influenza Vaccination". PharmacoEconomics 30 (8): 647–660. doi:10.2165/11599130-000000000-00000.
- Newall, A.T.; Wood, J.G.; Oudin, N.; MacIntyre, C.R. (2010). "Cost-effectiveness of pharmaceutical-based pandemic influenza mitigation strategies". Emerging Infectious Diseases 16 (2). doi:10.3201/eid1602.090571.
- Morbidity and Mortality Weekly Report (Centers for Disease Control) 58 (RR-8): 31. 2009 http://www.cdc.gov/mmwr/pdf/rr/rr5808.pdf
|url=missing title (help). "Students or other persons in institutional settings (e.g., those who reside in dormitories or correctional facilities) should be encouraged to receive vaccine to minimize morbidity and the disruption of routine activities during influenza epidemics"
- Thomas RE, Jefferson TO, Demicheli V, Rivetti D (2006). "Influenza vaccination for health-care workers who work with elderly people in institutions: a systematic review". Lancet Infect Dis 6 (5): 273–279. doi:10.1016/S1473-3099(06)70462-5. PMID 16631547.
- Skowronski DM, De Serres G (2009). "Is routine influenza immunization warranted in early pregnancy?". Vaccine 27 (35): 4754–70. doi:10.1016/j.vaccine.2009.03.079. PMID 19515466.
- Health Care Guideline: Routine Prenatal Care. Fourteenth Edition. By the Institute for Clinical Systems Improvement. July 2010.
- "WHO | World Health Organization". Who.int. Retrieved 2014-06-28.
- "Who Should Get Vaccinated Against Influenza". Centers for Disease Control. Retrieved 14 January 2014.
- "U.S. panel recommends all kids get the flu shot". CTV. February 27, 2008. "In Canada, the National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada, currently says that children between the age of six and 24 months should be considered a high priority for the flu vaccine."
- "Statement on Seasonal Influenza Vaccine for 2013-2014 - CCDR Vol.39 ACS-4 - Public Health Agency of Canada". Phac-aspc.gc.ca. 2013-11-14. Retrieved 2014-06-28.
- Fiore, AE; Uyeki; Broder, K; Finelli, L; Euler, GL; Singleton, JA; Iskander, JK; Wortley, PM et al. (August 2010). "Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010". MMWR Recomm Rep 59 (RR–8): 1–62. PMID 20689501.
- "Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) – United States, 2012-13 influenza season". MMWR Morb. Mortal. Wkly. Rep. 61 (32): 613–8. August 2012. ISSN 0149-2195. PMID 22895385.
- "Children, the Flu, and the Flu Vaccine"
- CDC - Influenza (Flu) | Vaccination: Summary for Clinicians
- Couch, Robert B.; Patricia Winokur, Rebecca Brady, Robert Belshe, Wilbur H. Chen, Thomas R. Cate, Bryndis Sigurdardottir, Amy Hoeper, Irene L. Graham, Robert Edelman, Fenhua He, Diane Nino, Jose Capellan, Frederick L. Ruben (1 November 2007). "Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects". Vaccine 25 (44): 7656. doi:10.1016/j.vaccine.2007.08.042.
- Tanner, Lindsey (2013-01-13). "Hospitals crack down on workers who refuse flu shots". NBC News. Retrieved 2014-06-28.
- how it's made
- New and Old Ways to Make Flu Vaccines, November 8, 2007, National Public Radio.
- WHO:Influenza vaccine viruses and reagents
- "Recommendations for the production and control of influenza vaccine (inactivated)". World Health Organization. Retrieved 27 May 2013.
- "Priming with DNA vaccine makes avian flu vaccine work better (NIH News)". October 3, 2011.
- "Novartis receives FDA approval for Flucelvax, the first cell-culture vaccine in US to help protect against seasonal influenza" (Press release). Novartis. November 20, 2012.
- "FDA approves first seasonal influenza vaccine manufactured using cell culture technology"
- "November 20, 2012 Approval Letter- Flucelvax"
- PATH, Oliver Wyman. Influenza Vaccine Strategies for Broad Global Access. 2007. http://www.path.org/files/VAC_infl_publ_rpt_10-07.pdf
- Bright, R. A.; Carter, D. M.; Daniluk, S.; Toapanta, F. R.; Ahmad, A.; Gavrilov, V.; Massare, M.; Pushko, P. et al. (May 2007). "Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin". Vaccine 25 (19): 3871–8. doi:10.1016/j.vaccine.2007.01.106. PMID 17337102.
- WHO article Global influenza surveillance[verification needed]
- Keeping ahead of flu comes down to guessing game : Health and Fitness : Knoxville News Sentinel
- WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases (pdf)
- WHO | Recommended composition of influenza virus vaccines for use in the 2014-2015 northern hemisphere influenza season
- WHO | Recommended composition of influenza virus vaccines for use in the 2014 southern hemisphere influenza season.
- Update on Influenza A (H1N1) 2009 Monovalent Vaccines
- "Seasonal Influenza Vaccine & Total Doses Distributed". WWD. 20 December 2013. Retrieved 26 December 2013.
- "Flu Vaccine Question". Pharmacistanswers.com. Retrieved 2014-06-28.
- Flulaval Package Insert; GSK August 2013
- Afluria Package Insert; Merck May 2013
- Fluarix Package Insert; Novartis May 2013
- Fluvirin Insert; Novartis July 2013
- Fluzone Package Insert; Sanofi Pasteur April 2013
- Webster, Robert; Walker, Elizabeth (2003). "Influenza". American Scientist 91 (2): 122. doi:10.1511/2003.2.122.
- Blakemore, C. (2006-04-09). "Battle of time, luck and science". The Sunday Times (London). Retrieved 2006-06-22.
- Hilleman, M (19 August 2002). "Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control". Vaccine 20 (25–26): 3068–87. doi:10.1016/S0264-410X(02)00254-2. PMID 12163258.
- "Ten things you need to know about pandemic influenza". World Health Organization. 14 October 2005. Archived from the original on 23 September 2009. Retrieved 26 September 2009.
- Valleron AJ, Cori A, Valtat S, Meurisse S, Carrat F, Boëlle PY (May 2010). "Transmissibility and geographic spread of the 1889 influenza pandemic". Proc. Natl. Acad. Sci. U.S.A. 107 (19): 8778–81. Bibcode:2010PNAS..107.8778V. doi:10.1073/pnas.1000886107. PMC 2889325. PMID 20421481.
- Mills CE, Robins JM, Lipsitch M (December 2004). "Transmissibility of 1918 pandemic influenza". Nature 432 (7019): 904–6. Bibcode:2004Natur.432..904M. doi:10.1038/nature03063. PMID 15602562.
- Donaldson LJ, Rutter PD, Ellis BM et al. (2009). "Mortality from pandemic A/H1N1 2009 influenza in England: public health surveillance study". BMJ 339: b5213. doi:10.1136/bmj.b5213. PMC 2791802. PMID 20007665.
- "ECDC Daily Update – Pandemic (H1N1) 2009 – January 18, 2010". European Centre for Disease Prevention and Control. 2010-01-18. Retrieved 2010-01-18.
- The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) (free online book) page 62
- Plotkin, S.L. and Plotkin, S.A. "A short history of vaccination." In: Vaccines, Stanley A. Plotkin, Walter A. Orenstein, Paul A. Offit, eds. Elsevier Health Sciences, 2008, pp. 6-7.
- Artenstein, A.W. "Influenza" In: Vaccines: A Biography Andrew W. Artenstein, ed. pp. 191-205.
- Hampson, AW. Vaccines for Pandemic Influenza. The History of our Current Vaccines, their Limitations and the Requirements to Deal with a Pandemic Threat. Ann Acad Med Singapore 2008;37:510-7.
- USFDA FDA approves first seasonal influenza vaccine manufactured using cell culture technology. November 20, 2012.
- USFDA FDA approves new seasonal influenza vaccine made using novel technology. Jan. 16, 2013.
- Landry, Nathalie; Brian J. Ward, Sonia Trépanier, Emanuele Montomoli, Michèle Dargis, Giulia Lapini, Louis-P. Vézina (2010-12-22). "Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza". PLOS One 5 (12). Bibcode:2010PLoSO...515559L. doi:10.1371/journal.pone.0015559. PMC 3008737. PMID 21203523. Retrieved 14 May 2013.
- CDC report Prevention and Control of Influenza published April 12, 2002.
- Osterholm, Michael T. (2005). "Preparing for the Next Pandemic". New England Journal of Medicine 352 (18): 1839–42. doi:10.1056/NEJMp058068. PMID 15872196.
- The Sky is Falling: An Analysis of the Swine Flu Affair of 1976
- "Influenza Genome Sequencing Project - Overview". National Institutes of Health - National Institute of Allergy and Infectious Diseases. Retrieved 27 May 2013.
- Tinder, Paul (June 7, 2013). "Vaccination programs at schools could reduce flu deaths among children at VND". VaccineNewsDaily. Retrieved 10 June 2013.
- World Health Organization. Acyte Respiratory Infections: Influenza. 2009. http://www.who.int/vaccine_research/diseases/ari/en/index1.html
- World Health Organization. Tables on the Clinical trials of pandemic influenza prototype vaccines. July 2009. http://www.who.int/vaccine_research/immunogenicity/immunogenicity_table.xls
- US Food & Drug Administration. FDA Approves Vaccines for 2009 H1N1 Influenza Virus Approval Provides Important Tool to Fight Pandemic. September 15, 2009. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm
- "First Quadrivalent Vaccine Against Seasonal Flu Wins FDA Approval"
- "FDA approves first quadrivalent vaccine to prevent seasonal influenza"
- "December 14, 2012 Approval Letter- Fluarix Quadrivalent"
- Du, Lanying; Zhou, Yusen; Jiang, Shibo (2010). "Research and development of universal influenza vaccines". Microbes and Infection 12 (4): 280–6. doi:10.1016/j.micinf.2010.01.001. PMID 20079871.
- Seattle's Theraclone makes a 'first step' on long road to universal flu vaccine. The Seattle Times.
- Dynavax Reports Positive Data on Universal Flu Vaccine Candidate. Rita Biotech.
- VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study. Fierce Biotech.
- Johnson & Johnson pursues vaccine firm. Charleston Gazette.
- "Inovio Pharmaceuticals, Inc. Immunizes First Subject In U.S. Influenza DNA Vaccine Clinical Trial". Reuters.
- Immune Targeting Systems - About Us
- "Universal Influenza Vaccine Tested Successfully In Humans".
- "Universal flu jab works in people". BBC News Online. 4 January 2008.
- The Wistar Institute obtains patent for universal flu vaccine technology. Wistar Institute.
- NIH Scientists Advance Universal Flu Vaccine. NIH.
- Inovio Biomedical's SynCon preventive DNA vaccine receives approval in Korea for Phase I clinical trial
- "Scientific Paper on Inovio Pharmaceuticals SynCon(TM) DNA Vaccines and Intradermal DNA Delivery Technology One of Most Cited Articles in the Journal Vaccine". October 14, 2010.
- BBC: 'Super antibody' fights off flu
- Independent: Scientists hail the prospect of a universal vaccine for flu
- "Universal Flu Vaccine On The Horizon: Researchers Find 'Super Antibody'" The Huffington Post. July 28, 2011
- Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain
- . doi:10.1128/JVI.00641-13. Missing or empty
- . doi:10.1016/j.coviro.2013.07.007. Missing or empty
- Wang TT, Tan GS, Hai R, Pica N, Ngai L, Ekiert DC, Wilson IA, García-Sastre A, Moran TM (November 2010). "Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes.". Proc Natl Acad Sci U S A 107 (44): 18979–84. Bibcode:2010PNAS..10718979W. doi:10.1073/pnas.1013387107. PMC 2973924. PMID 20956293.
- Hidden weakness could yield universal flu vaccine - health - February 24, 2009 - New Scientist
- "BiondVax Begins Phase IIa Study for Universal Flu Vaccine". October 14, 2010.
- "Dynavax Presents Data From Novel Universal Flu Vaccine Candidate".
- Immune Targeting Systems - FP01 Influenza
- Lambert and Fauci; Fauci, Anthony S. (2010). "Influenza Vaccines for the Future". NEJM 363 (21): 2036–44. doi:10.1056/NEJMra1002842. PMID 21083388.
- "H1N1 Gives Clues to Universal Flu Vaccine". January 18, 2011.
- Wrammert, Koutsonanos, D., Li, G.-M. et al. (January 2011). "Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection". JEM 208: 181–193. doi:10.1084/jem.20101352.
- "A vaccine for all flu seasons". Spring 2011.
- Roos, Robert. "FDA expert: Universal flu vaccine still 5-10 years off". Center for Infectious Disease Research and Policy (CIDRAP). Retrieved Feb 13, 2013.
- Influenza Report (online book) chapter Avian Influenza by Timm C. Harder and Ortrud Werner
- UAE Equestrian & Racing Federation
- FEI guidelines
- McNeil, Donald G. Jr. (May 2, 2006). "Turning to Chickens in Fight With Bird Flu". The New York Times.
- SciDev.Net article Bird flu warning over partial protection of flocks published August 16, 2006
- FAO Recommendations on the Prevention, Control and Eradication of Highly Pathogenic Avian Influenza (HPAI) in Asia http://www.fao.org/docs/eims/upload/246982/aj126e00.pdf
- Yen, Hui-Ling; Joseph Sriyal Malik Peiris (21 June 2012). "Virology: Bird flu in mammals". Nature 486 (7403): 332–333. Bibcode:2012Natur.486..332Y. doi:10.1038/nature11192. PMID 22722190. Retrieved 27 May 2013.
- National Hog Farmer article Swine Flu Virus Turns Endemic published September 15, 2007
- livestock.novartis.com Custom Vaccines: Swine
- Karaca K, Dubovi E, Siger L, Robles A, Audonnet J, Jiansheng Y, Nordgren R, Minke J (2007). "Evaluation of the ability of canarypox-vectored equine influenza virus vaccines to induce humoral immune responses against canine influenza viruses in dogs". Am. J. Vet. Res. 68 (2): 208–12. doi:10.2460/ajvr.68.2.208. PMID 17269888.
- The Compelling Need for Game-Changing Influenza Vaccines CIDRAP Comprehensive Influenza Vaccine Initiative (CCIVI)
- Vaccine Strains vs. Circulating Strains
- NHS seasonal flu vaccination campaign NHS flu fighter
- History of past WHO seasonal influenza vaccine composition recommendations
- Vaccine Research Center Information from NIAID regarding preventative vaccine research studies
- About the flu jab (NHS Direct)
- World Health Organization's Initiative for Vaccine Research Influenza web page
- Influenza Strategies for Broad Global Access
- PATH's Vaccine Resource Library influenza resources
- Orr, Pamela (2000). "Influenza vaccination for health care workers: A duty of care". Canadian Journal of Infectious Diseases 11 (5): 225–6. PMC 2094777. PMID 18159292.
- CDC 2009 H1N1 Influenza Vaccine Supply Status
- CDC Vaccine Information Statement Inactivated Inﬂuenza Vaccine
- Read Congressional Research Service (CRS) Reports regarding Influenza and vaccines
- Influenza Research Database – Database of influenza genomic sequences and related information.
- Health-EU portal EU response to influenza
- European Commission - Public Health EU coordination on Pandemic (H1N1) 2009
- Centers for Disease Control and Prevention - Vaccines and Preventable Diseases - Seasonal Influenza (Flu) Vaccination
- Centers for Disease Control and Prevention - Misconceptions about Seasonal Influenza and Influenza Vaccines
- Influenza Vaccine (NYTimes / Adam)
- "FluMist Quadrivalent Prescribing Information"
- "Fluarix Quadrivalent Prescribing Information"
- "Flucelvax Prescribing Information"
- Transdermal Flu Patch Vaccine