Pneumococcal vaccine

A pneumococcal vaccine is a vaccine against Streptococcus pneumoniae.[1]

Types include: pneumococcal polysaccharide vaccine and pneumococcal conjugate vaccine

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[2]

Recommendations

Worldwide

Pneumococcal vaccines Accelerated Development and Introduction Plan (PnemoADIP) is a program to accelerate the evaluation and access to new pneumococcal vaccines in the developing world. PneumoADIP is funded by the Global Alliance for Vaccines and Immunization (GAVI). Thirty GAVI countries have expressed interest in participating by 2010. PneumoADIP aims to save 5.4 million children by 2030.[3]

A pilot Advance Market Commitment (AMC) to develop a vaccine against pneumococcus was launched in June 2009 as a strategy to address two of the major policy challenges to vaccine introduction: a lack of affordable vaccines on the market, and insufficient commercial incentives to develop vaccines for diseases concentrated in developing countries. Under the terms of an AMC, donors make a legally binding guarantee that,if a future vaccine is developed against a particular disease, they will purchase a predetermined amount at an agreed-upon price. The guarantee is linked to safety and efficacy standards that the vaccine must meet and is structured in a way to allow several firms to compete to develop and produce the best possible new product. AMCs reduce risk to donor governments by eliminating the need to fund individual research and development projects that may never produce a vaccine. If no company produces a vaccine that meets the predetermined standards, governments (and thus their taxpayers) spend nothing. For the bio-pharmaceutical industry, AMCs create a guaranteed market, with a promise of returns that would not normally exist. For developing countries, AMCs provide funding to ensure that those vaccines will be affordable once they have been developed. It is estimated that the pneumococcal AMC could prevent more than 1.5 million childhood deaths by 2020.[4]

USA

In the USA, a heptavalent pneumococcal conjugate vaccine (PCV 7) (e.g. Prevenar[5]) was recommended for all children aged 2–23 months and for at-risk children aged 24–59 months in 2000. The normal 4-dose series is given at 2, 4, 6 & 12–14 months of age. In February 2010, a pneumococcal congugate vaccine which protects against an additional 6 serotypes was introduced (PCV 13 / brand name: Prevnar 13) and can be given instead of the original Prevnar.[6][7] Similar 9-, and 10-valent vaccines have been tested. Protection is good against deep pneumococcal infections (especially septicemia and meningitis). However, if a child is exposed to a serotype of pneumococcus that is not contained in the vaccine, he/she is not afforded any protection. This limitation, and the ability of capsular-polysaccharide conjugate vaccines to promote the spread of non-covered serotypes, has led to research into vaccines that would provide species-wide protection.

Pneumococcal polysaccharide vaccine (Pneumovax is one brand) gives at least 85% protection in those under 55 years of age for five years or longer. Immunization is suggested for those at highest risk of infection, including those 65 years or older; generally the vaccine should be a single lifetime dose, as there is a high risk of side effects if repeated. The standard 23-valent vaccines are ineffective for children under two years old.

The current guidelines of the American College of Physicians call for administration of the immunization between ages 2 and 65 when indicated, or at age 65. If someone received the immunization before age 60, the guidelines call for a one-time revaccination.

Revaccination at periodic intervals is also indicated for those with other conditions such as asplenia or nephrotic syndrome.

UK

It was announced in February 2006 that the UK government would introduce vaccination with the conjugate vaccine in children aged 2, 4 and 13 months.[8][9] This included changes to the immunisation programme in general.[10] In 2009, the European Medicines Agency approved the use of a 10 valent pneumcoccal conjugate vaccine for use in Europe.[11] The 13 valent pneumococcal vaccine was introduced in the routine immunization schedule of the UK in April 2010.

South Africa

Pneumovax 23 is used, and according to the enclosed patient information leaflet, has a reported 76% to 92% protective efficacy (pneumococcal types 1, 2, 3, 4, 5, 6B**, 7F, 8, 9N, 9V**, 10A, 11A, 12F, 14**, 15B, 17F, 18C, 19A**, 19F**, 20, 22F, 23F** and 33F** are included, where ** indicates drug resistant pneumococcal infections; these are the 23 most prevalent or invasive pneumococcal types of Streptococcus pneumoniae).

Mechanism

Polysaccharide vaccine

The polysaccharide vaccine most commonly used today. consists of purified polysaccharides from 23 serotypes (1, 2, 3, 4, 5, 6b, 7F, 8,9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F).[12] Immunity is induced primarily through stimulation of B-cells which release IgM[12] without the assistance of T cells.[13]

This immune response is less robust than the response provoked by conjugated vaccines, which has several consequences. The vaccine is ineffective in children less than two years old, presumably due to their less mature immune systems.[12] Non-responders are also common amongst older adults.[12] Immunization is not lifelong, so individuals must be re-vaccinated at age 65 if at least 5 years after initial vaccination.[12] Since no mucosal immunity is provoked, the vaccine does not affect carrier rates, promote herd immunity, or protect from upper or lower respiratory tract infections.[12] Finally, provoking immune responses using unconjugated polysaccharides from the capsules of other bacteria, such as H. influenzae, have proven significantly more difficult.[12]

Conjugated vaccine

The conjugated vaccine consists of capsular polysaccharides covalently bound to the diphtheria toxoid CRM197, which is highly immunogenic but non-toxic.[12] This combination provokes a significantly more robust immune response by recruiting CRM197-specific type 2 helper T cells, which allow for immunoglobulin type switching (to produce non-IgM immunoglobulin) and production of memory B cells.[12] Among other things, this results in mucosal immunity and eventual establishment of lifelong immunity after several exposures.[12] The main drawbacks to conjugated vaccines are that they only provide protection against a subset of the serotypes covered by the polysaccharide vaccines.

Research

Due to the geographic distribution of pneumococcal serotypes, additional research is needed to find the most efficacious vaccine for developing-world populations. In a previous study, the most common pneumococcal serotypes or groups from developed countries were found to be, in descending order, 14, 6, 19, 18, 9, 23, 7, 4, 1 and 15. In developing countries the order was 6, 14, 8, 5, 1, 19, 9, 23, 18, 15 and 7.[14] In order to further pneumococcal vaccine research and reduce childhood mortality, five countries and the Bill & Melinda Gates Foundation established a pilot Advance Market Commitment for pneumococal vaccines worth US$1.5 billion. Advance Market Commitments are a new approach to public health funding designed to stimulate the development and manufacture of vaccines for developing countries.[15]

There is currently research into producing vaccines than can be given into the nose rather than by injection.[16] [17] It is believed that this improves vaccine efficacy and also avoids the need for injection.

The development of serotype-specific anticapsular monoclonal antibodies has also been researched in recent years. These antibodies have been shown to prolong survival in a mouse model of pneumococcal infection characterized by a reduction in bacterial loads and a suppression of the host inflammatory response.[18][19] Additional pneumococcal vaccine research is taking place to find a vaccine that offers broad protection against pneumococcal disease.[20]

References

  1. ↑ Pneumococcal Vaccines at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ↑ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
  3. ↑ "PneumoADIP website"
  4. ↑ "Pneumococcal AMC GAVI webpage"
  5. ↑ "Prevenar — Annex I: Summary of Product Characteristics" (PDF). E.M.E.A.
  6. ↑ Wilson D (24 February 2010). "Vaccine Approved for Child Infections". The New York Times.
  7. ↑ "Prevnar 13". Vaccines, Blood & Biologics. U.S. Food and Drug Administration. 2012-01-12.
  8. ↑ "Children to be given new vaccine". BBC News. 8 February 2006.
  9. ↑ "Pneumococcal vaccine added to the childhood immunisation programme" (Press release). 8 February 2006.
  10. ↑ "Changes to the immunisation programme in the UK". Meningitis Research Foundation.
  11. ↑ "Synflorix, GlaxoSmithKline's pneumococcal vaccine receives European authorisation" (Press release). GlaxoSmithKline. 31 March 2009.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7 12.8 12.9 Pletz MW, Maus U, Krug N, Welte T, Lode H (September 2008). "Pneumococcal vaccines: mechanism of action, impact on epidemiology and adaption of the species". Int. J. Antimicrob. Agents 32 (3): 199–206. doi:10.1016/j.ijantimicag.2008.01.021. PMID 18378430.
  13. ↑ Stein KE (June 1992). "Thymus-independent and thymus-dependent responses to polysaccharide antigens". J. Infect. Dis. 165 (Suppl 1): S49–52. doi:10.1093/infdis/165-supplement_1-s49. PMID 1588177.
  14. ↑ Sniadack DH, Schwartz B, Lipman H, Bogaerts J, Butler JC, Dagan R, Echaniz-Aviles G, Lloyd-Evans N, Fenoll A (June 1995). "Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children--implications for vaccine strategies". Pediatr Infect Dis J 14 (6): 503–10. doi:10.1097/00006454-199506000-00007. PMID 7667055.
  15. ↑ GAVI Alliance, World Bank. "Saving Lives with New Vaccines: Advance Market Commitments" (PDF).
  16. ↑ Hanniffy SB, Carter AT, Hitchin E, Wellsa JM. (2007). "Mucosal delivery of a Pneumococcal vaccine using Lactococcus lactis affords protection against respiratory infection". J Infect Dis 195 (2): 185–193. doi:10.1086/509807. PMID 17191163.
  17. ↑ Malley R. Lipsitch M, Stack A, Saladino R, Fleisher G, Pelton S, Thompson C, Briles D, Anderson P. (2001). "Intranasal Immunization with Killed Unencapsulated Whole Cells Prevents Colonization and Invasive Disease by Capsulated Pneumococci". Infect Immun 69 (8): 4870–3. doi:10.1128/IAI.69.8.4870-4873.2001. PMC 98576. PMID 11447162.
  18. ↑ Burns T, Abadi M, Pirofski L (2005). "Modulation of the Lung Inflammatory Response to Serotype 8 Pneumococcal Infection by a Human Immunoglobulin M Monoclonal Antibody to Serotype 8 Capsular Polysaccharide". Infect Immun 73 (8): 4530–8. doi:10.1128/IAI.73.8.4530-4538.2005. PMC 1201218. PMID 16040964.
  19. ↑ Fabrizio K, Groner A, Boes M, Pirofski L (2007). "A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection". Clin Vaccine Immunol 14 (4): 382–90. doi:10.1128/CVI.00374-06. PMC 1865609. PMID 17301214.
  20. ↑ "Acute Respiratory Infections (Update September 2009): Streptococcus pneumoniae". Initiative for Vaccine Research (IVR). World Health Organization.

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