Pneumococcal conjugate vaccine
|Target disease||Streptococcus pneumoniae|
|Trade names||Prevnar 13, Synflorix, others|
|(what is this?)|
Pneumococcal conjugate vaccine (PCV) is a pneumococcal vaccine and a conjugate vaccine used to protect infants, young children, and adults against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). It contains purified capsular polysaccharide of pneumococcal serotypes conjugated to a carrier protein to improve antibody response compared to the pneumococcal polysaccharide vaccine. The World Health Organization (WHO) recommends the use of the conjugate vaccine in routine immunizations given to children.
There are two types of PCV available with the brand names Prevnar 13 and Synflorix. The brand Pneumosil was prequalified by the WHO in 2020.
Pneumosil is a decavalent pneumococcal conjugate vaccine produced by the Serum Institute of India. It contains the serotypes 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, and 23F, and was prequalified by WHO in January 2020.
Prevnar 13 (PCV13) is produced by Wyeth and replaced Prevnar. It is a tridecavalent vaccine, it contains thirteen serotypes of pneumococcus (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) which are conjugated to diphtheria carrier protein. Prevnar 13 was approved for use in the European Union in December 2009. On February 2010, Prevnar 13 was approved in the United States to replace the pneumococcal 7-valent conjugate vaccine. After waiting for the outcome of a trial underway in the Netherlands, the Centers for Disease Control and Prevention (CDC) recommended the vaccine for adults over age 65 in August 2014.
Prevnar (PCV7) was a heptavalent vaccine, meaning that it contains the cell capsule sugars of seven serotypes of the bacteria S. pneumoniae (4, 6B, 9V, 14, 18C, 19F, and 23F), conjugated with diphtheria proteins. It was manufactured by Wyeth (which was acquired by Pfizer). Prevnar was approved for use in the United States in February 2000, and vaccination with Prevnar was recommended for all children younger than two years, and for unvaccinated children between 24 and 59 months old who were at high risk for pneumococcal infections.
Prevnar was produced from the seven most prevalent strains of Streptococcus pneumoniae bacteria in the U.S. The bacterial capsule sugars, a characteristic of these pathogens, are linked to CRM197, a nontoxic recombinant variant of diphtheria toxin (Corynebacterium diphtheriae).
The vaccine's polysaccharide sugars are grown separately in soy peptone broths. Through reductive amination, the sugars are directly conjugated to the protein carrier CRM197 to form the glycoconjugate. CRM197 is grown in C. diphtheriae strain C7 in a medium of casamino acids and yeast extracts.
The original seven-valent formulation contained serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, and resulted in a 98 % probability of protection against these strains, which caused 80 % of the pneumococcal disease in infants in the U.S. PCV7 is no longer produced.
In 2010, Pfizer introduced Prevnar 13, which contains six additional strains (1, 3, 5, 6A, 19A and 7F), which protect against the majority of the remaining pneumococcal infections.
In March 2020, Pfizer announced its intent to file an adult indication for its 20-valent pneumococcal conjugate vaccine candidate 20vPnC with the Food and Drug Administration following results from a Phase III clinical trial. This candidate contains the serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F.
Synflorix (PCV10) is produced by GlaxoSmithKline. It is a decavalent vaccine, it contains ten serotypes of pneumococcus (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) which are conjugated to a carrier protein. Synflorix received a positive opinion from the European Medicines Agency for use in the European Union in January 2009 and GSK received European Commission authorization to market Synflorix in March 2009.
A pentadecavalent vaccine candidate, PCV15 with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, and 33F, has been developed by GlaxoSmithKline and was moved to Phase III clinical trial in 2018.
Schedule of vaccination
As with all immunizations, whether it is available or required, and under what circumstances, varies according to the decisions made by local public health agencies.
Children under the age of two years fail to mount an adequate response to the 23-valent adult vaccine, and so a pneumococcal conjugate vaccine is used. While this covers only seven strains out of more than ninety strains, these seven strains cause 80% to 90% of cases of severe pneumococcal disease, and it is considered to be nearly 100% effective against these strains.
Children at special risk (e.g., sickle cell disease and asplenia) require as full protection as can be achieved using the conjugated vaccine, with the more extensive polysaccharide vaccine given after the second year of life:
|Age||2–6 months||7–11 months||12–23 months|
|Conjugated vaccine||3 × monthly dose||2 × monthly dose||2 doses, 2 months apart|
|Further dose in second year of life|
|23-valent vaccine||Then after 2nd birthday single dose of 23-valent|
In 2001, the Centers for Disease Control and Prevention (CDC), upon advice from its Advisory Committee on Immunization Practices, recommended the vaccine be administered to every infant and young child in the United States. The resulting demand outstripped production, creating shortages not resolved until 2004. All children, according to the U.S. vaccination schedule, should receive four doses, at two months, four months, six months, and again between one year and fifteen months of age.
Prevnar-7 is designed to stop seven of about ninety pneumococcal serotypes which have the potential to cause invasive pneumococcal disease (IPD). In 2010, a 13-valent vaccine was introduced. Each year, IPD kills approximately one million children worldwide. Since approval, Prevnar's efficacy in preventing IPD has been documented by a number of epidemiologic studies. There is evidence that other people in the same household as a vaccinee also become relatively protected. There is evidence that routine childhood vaccination reduces the burden of pneumococcal disease in adults and especially high-risk adults, such as those living with HIV/AIDS.
The vaccine is, however, primarily developed for the U.S. and European epidemiological situation, and therefore it has only a limited coverage of serotypes causing serious pneumococcal infections in most developing countries.
Evidence supporting addition to routine vaccination schedules
After introduction of the pneumococcal conjugate vaccine in 2000, several studies described a decrease in invasive pneumococcal disease in the United States. One year after its introduction, a group of investigators found a 69% drop in the rate of invasive disease in those of less than two years of age. By 2004, all-cause pneumonia admission rates had declined by 39% (95% CI 22–52) and rates of hospitalizations for pneumococcal meningitis decreased by 66% (95% CI 56.3-73.5) in children younger than 2.
Vaccination in low-income countries
Pneumococcal disease is the leading vaccine-preventable killer of young children worldwide, according to the World Health Organization (WHO). It killed more than 500,000 children younger than five years of age in 2008 alone. Approximately ninety percent of these deaths occur in the developing world. Historically 15–20 years pass before a new vaccine reaches one quarter of the population of the developing world.
Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP) was a GAVI Alliance (GAVI) funded project to accelerate the introduction of pneumococcal vaccinations into low-income countries through partnerships between countries, donors, academia, international organizations and industry. GAVI continues this work and as of March 2013, 25 GAVI-eligible and supported countries have introduced the pneumococcal conjugate vaccine. Further, 15 additional GAVI countries have plans to introduce the vaccine into their national immunization program and 23 additional countries have approved GAVI support to introduce the vaccine.
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