|Target disease||Haemophilus influenzae type b|
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Haemophilus influenzae type B vaccine is a vaccine used to prevent Haemophilus influenzae type b (Hib) infection. In countries that include it as a routine vaccine, rates of severe Hib infections have decreased more than 90%. It has therefore resulted in a decrease in the rate of meningitis, pneumonia, and epiglottitis.
It is recommended by both the World Health Organization and Centers for Disease Control and Prevention. Two or three doses should be given before six months of age. In the United States a fourth dose is recommended between 12 and 15 months of age. The first dose is recommended around six weeks of age with four weeks between doses. If only two doses are used, another dose later in life is recommended. It is given by injection into a muscle.
Severe side effects are uncommon. About 20 to 25% of people develop pain at the site of injection while about 2% develop a fever. There is no clear association with severe allergic reactions. The Hib vaccine is available by itself, in combination with the diphtheria/tetanus/pertussis vaccine, and in combination with the hepatitis B vaccine, among others. All Hib vaccines that are currently used are conjugate vaccine.
An initial Hib vaccine was developed in 1977 which was replaced by a more effective formulation in the 1990s. As of 2013, 184 countries include it in their routine vaccinations. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost of a pentavalent vaccine which includes Hib in the developing world was 15.40 USD per dose as of 2014. In the United States it costs about 25 to 50 USD per dose.
- 1 Medical uses
- 2 Side effects
- 3 Mechanisms of action
- 4 Developing world
- 5 History
- 6 References
Hib conjugate vaccines have been shown to be universally effective against all manifestations of Hib disease, with a clinical efficacy among fully vaccinated children estimated to be between 95–100%. The vaccine has also been shown to be immunogenic in patients at high risk of invasive disease. Hib vaccine is not effective against non-type B Haemophilus influenzae. However, non-type B disease is rare in comparison to pre-vaccine Haemophilus influenzae type B disease.
Prior to introduction of the conjugate vaccine, Hib was a leading cause of childhood meningitis, pneumonia, and epiglottitis in the United States, causing an estimated 20,000 cases a year in the early 1980s, mostly in children under 5 years old. Since routine vaccination began, the incidence of Hib disease has declined by greater than 99%, effectively eliminating Hib as a public health problem. Similar reductions in disease occurred after introduction of the vaccine in Western Europe and developing countries.
Although Hib vaccine is given to children, Hib infections have also decreased in adults. This decrease occurred because of herd immunity; children infected with Hib carry the bacteria in their nasal passages while clearing the infection. These Hib-carrying children would regularly infect adults. The practice of vaccinating children eliminated the source of the bacteria, reducing the rate of Hib in adults.
The CDC and WHO currently recommend that all infants be vaccinated using a polysaccharide-protein conjugate Hib vaccine, starting after the age of 6 weeks. The vaccination is also indicated in asplenic patients.
Clinical trials and ongoing surveillance have shown Hib vaccine to be safe. In general, adverse reactions to the vaccine are mild. The most common reactions are mild fever, loss of appetite, transient redness, swelling, or pain at the site of injection, occurring in 5–30% of vaccine recipients. More severe reactions are extremely rare.
Mechanisms of action
Haemophilus influenzae type b is a bacterium with a polysaccharide capsule; the main component of this capsule is polyribosyl ribitol phosphate (PRP). Anti-PRP antibodies have a protective effect against Hib infections. Thus, purified PRP was considered a good candidate for a vaccine. However, the antibody response to PRP diminished rapidly after administration. This problem was due to recognition of the PRP antigen by B cells, but not T cells. In other words, even though B cell recognition was taking place, T cell recruitment (via MHC class II) was not, which compromised the immune response. This interaction with only B cells is termed T-independent (TI). This process also inhibits the formation of memory B cells, thus compromising long term immune system memory. 
PRP covalently linked to a protein carrier was found to elicit a greater immune response than the polysaccharide form of the vaccine. This is due to the protein carrier being highly immunogenic in nature. The conjugate formulations show responses which are consistent with T-cell recruitment (namely a much stronger immune response). A memory effect (priming of the immune system against future attack by Hib) is also observed after administration; indicative that memory B cell formation is also improved over that of the polysaccharide form. Since optimal contact between B cells and T cells is required (via MHC II) to maximize antibody production, it is reasoned that the conjugate vaccine allows B cells to properly recruit T cells, this is in contrast to the polysaccharide form in which it is speculated that B cells do not interact optimally with T cells leading to the TI interaction. 
Introduction of Hib vaccine in developing countries lagged behind that in developed countries for several reasons. The expense of the vaccine was large in comparison to the standard EPI vaccines. Poor disease surveillance systems and inadequate hospital laboratories failed to detect the disease, leading many experts to believe that Hib did not exist in their countries. And health systems in many countries were struggling with the current vaccines they were trying to deliver.
GAVI and the Hib Initiative
In order to remedy these issues, the GAVI Alliance took active interest in the vaccine. GAVI offers substantial subsidization of Hib vaccine for countries interested in using the vaccine, as well as financial support for vaccine systems and safe injections. In addition, GAVI created the Hib Initiative to catalyze uptake of the vaccine. The Hib Initiative uses a combination of collecting and disseminating existing data, research, and advocacy to assist countries in the making a decision about using the Hib vaccine. Currently[update], 61 out of 72 low-income countries are planning on introducing the vaccine by the end of 2009.
The first Hib vaccine licensed was a pure polysaccharide vaccine, first marketed in the US in 1985. Similar to other polysaccharide vaccines, immune response to the vaccine was highly age-dependent. Children under 18 months of age did not produce a positive response for this vaccine. As a result, the age group with the highest incidence of Hib disease was unprotected, limiting the usefulness of the vaccine. The vaccine was withdrawn from the market in 1988.
The shortcomings of the polysaccharide vaccine led to the production of the Hib polysaccharide-protein conjugate vaccine. Attaching Hib polysaccharide to a protein carrier greatly increased the ability of the immune system of young children to recognize the polysaccharide and develop immunity. There are currently three types of conjugate vaccine, utilizing different carrier proteins for the conjugation process, all of which are highly effective and safe: inactivated tetanospasmin (also called tetanus toxoid), mutant diphtheria protein, and meningococcal group B outer membrane protein.
Multiple combinations of Hib and other vaccines have been licensed in the United States, reducing the number of shots necessary to vaccinate a child. Hib vaccine combined with diphtheria-tetanus-pertussis–polio vaccines and Hepatitis B vaccines are available in the US. The World Health Organization (WHO) has certified several Hib vaccine combinations, including a pentavalent diphtheria-pertussis-tetanus-hepatitis B-Hib, for use in developing countries. There is not yet sufficient evidence on how effective this combined pentavalent vaccine is in relation to the individual vaccines.
- "Haemophilus influenzae type b (Hib) Vaccination Position Paper – July 2013." (PDF). Wkly Epidemiol Rec. 88 (39): 413–26. Sep 27, 2013. PMID 24143842.
- "Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older. Recommendations of the immunization practices advisory committee (ACIP).". MMWR Recomm Rep. 40 (RR-1): 1–7. Jan 11, 1991. PMID 1899280.
- "Hib (Haemophilus Influenzae Type B)". Retrieved 30 March 2016.
- "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016.
- "Vaccine, Pentavalent". International Drug Price Indicator Guide. Retrieved 7 December 2015.
- Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 313. ISBN 9781284057560.
- "Recommendation of the Immunization Practices Advisory Committee (ACIP) Polysaccharide Vaccine for Prevention of Haemophilus influenzae Type b Disease". MMWR Weekly. 34 (15): 201–5. 1985-04-19. ISSN 0149-2195. Retrieved 2008-10-03.
- "Haemophilus influenzae Disease (Including Hib)". Disease Listing. Centers for Disease Control and Prevention. 2012-09-25. Retrieved 2014-01-31.
- Kelly, Dominic F.; Moxon, E. Richard; Pollard, Andrew J. (2004-10-01). "Haemophilus influenzae type b conjugate vaccines". Immunology. 113 (2): 163–174. doi:10.1111/j.1365-2567.2004.01971.x. ISSN 1365-2567. PMC . PMID 15379976.
- Finn, Adam (2004-01-01). "Bacterial polysaccharide–protein conjugate vaccines". British Medical Bulletin. 70 (1): 1–14. doi:10.1093/bmb/ldh021. ISSN 0007-1420. PMID 15339854.
- "Hib Initiative". Retrieved 2008-10-03.
61 of 72 GAVI countries have introduced or will introduce Hib vaccine into their routine immunization program [sic] by 2009
- Centers for Disease Control and Prevention (2006). Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases (9th ed.). Washington, D.C.: Public Health Foundation.
- Bar-On, ES; Goldberg, E; Hellmann, S; Leibovici, L (18 April 2012). "Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB).". The Cochrane database of systematic reviews. 4: CD005530. doi:10.1002/14651858.CD005530.pub3. PMID 22513932.