Pneumococcal vaccine

Pneumococcal vaccines are vaccines against the bacterium Streptococcus pneumoniae.[1] Their use can prevent some cases of pneumonia, meningitis, and sepsis.[1] There are two types of pneumococcal vaccines: conjugate vaccines and polysaccharide vaccines.[1] They are given by injection either into a muscle or just under the skin.[1]

Pneumococcal vaccine
Pneumovax
Vaccine description
Target diseaseStreptococcus pneumoniae
TypeConjugate vaccine
Clinical data
AHFS/Drugs.comMonograph
ATC code
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
Identifiers
ChemSpider
  • none

The World Health Organization (WHO) recommends the use of the conjugate vaccine in the routine immunizations given to children.[1] This includes those with HIV/AIDS.[1] The recommended three or four doses are between 71 and 93% effective at preventing severe pneumococcal disease.[1] The polysaccharide vaccines, while effective in healthy adults, are not effective in children less than two years old or those with poor immune function.[1]

These vaccines are generally safe.[1] With the conjugate vaccine about 10% of babies develop redness at the site of injection, fever, or change in sleep.[1] Severe allergies are very rare.[1]

The first pneumococcal vaccine was developed in the 1980s.[1] It is on the World Health Organization's List of Essential Medicines.[2]

Recommendations
Prevenar13

Worldwide

Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP) 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 by GAVI 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]

Doctors without borders has criticized GAVI's pneumococcal AMC for not encouraging innovation, discouraging competition from new market entrants, and raising vaccine costs. They said that it had allowed Pfizer and GlaxoSmithKline to maintain a duopoly, while making it more difficult for the Serum Institute of India to sell their cheaper vaccine. The duopoly allowed price discrimination; somewhat higher prices for GAVI, and unaffordable prices (about ten time the GAVI price) for middle-income countries too rich for GAVI aid.[5] The pneumoccocal program (unlike previous market-shaping programs from GAVI[6]) did not include any mechanism for increasing competition.[7]

The Humanitarian Mechanism makes the pneumococcal vaccine available to humanitarian actors (but not governments) at a lower than normal price during humanitarian emergencies.[8]

India

In May 2017, the Government of India decided to include pneumococcal conjugate vaccine in its Universal Immunization Programme.[9]

United States
Diagram with visual representation of the current indications for both the Prevnar and the Pneumovax.[10]

In the United States, a heptavalent pneumococcal conjugate vaccine (PCV 7) (e.g. Prevnar, called Prevenar in some countries[11]) was recommended for all children aged 2–23 months and for at-risk children aged 24–59 months in 2000. The normal four-dose series is given at 2, 4, 6 and 12–14 months of age. In February 2010, a pneumococcal conjugate vaccine which protects against an additional six serotypes was introduced (PCV 13/brand name: Prevnar 13) and can be given instead of the original Prevnar.[12][13]

Pneumococcal polysaccharide vaccine (PPV, 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 the administration of the immunization between ages two and 65 when indicated, or at age 65. If someone received the immunization before age 60, the guidelines call for one-time revaccination. Majority of pharmacists indicate that they recommend all adults 65 and older receive a pneumococcal vaccination. They are generally educated on ACIP/CDC recommendations and believe that all people, regardless of age, should also be caught up on them. [14]

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.[15][16] This included changes to the immunisation programme in general.[17] In 2009, the European Medicines Agency approved the use of a 10 valent pneumococcal conjugate vaccine for use in Europe.[18] The 13 valent pneumococcal vaccine was introduced in the routine immunization schedule of the UK in April 2010.

South Africa

The 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) were introduced into the national Expanded Program on Immunization (EPI) in South Africa in 2009 and 2011, respectively. South Africa became the first African country – and the first nation in the world with a high HIV prevalence – to introduce PCV7 into its routine immunization program.[19] Rates of invasive pneumococcal disease – including cases caused by antibiotic-resistant bacteria – have fallen substantially in South Africa following the introduction of PCV7. Among children under two years of age, the overall incidence of IPD declined nearly 70% after PCV introduction, and rates of IPD caused by bacteria specifically targeted by the vaccine decreased nearly 90%.[20] Due to the indirect protection conferred by herd immunity, a significant decline in IPD in children and in unvaccinated adults has also been shown.[20] Pneumovax 23 is used for all ages 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).

Canada

Health Canada's general recommendations are 13-valent pneumococcal conjugate vaccine (PCV 13) vaccine for children aged 2 months to 18 years and 23-valent pneumococcal polysaccharide vaccine (PPV 23) vaccine for adults.[21]

Adverse reactions

Conjugate vaccine

Local reactions such as pain, swelling, or redness occur in up to 50% of those vaccinated with PCV13; of these, 8% are considered severe. Local reactions are more likely after the 4th dose than the earlier doses.[22] In clinical trials, fever greater than 100.4 F (38 C) was reported at a rate of 24-35% following any dose in the primary series and nonspecific symptoms such as decreased appetite or irritability occur in up to 80% of recipients.[22] In a vaccine safety datalink study, febrile seizures occurred in roughly 1 in 83,000 to 1 in 6,000 children given PCV 13, and 1 in 21,000 to 1 in 2,000 of those who were given PCV13 and trivalent influenza vaccine at the same time.[22]

Mechanism

Polysaccharide vaccine

The pneumococcal 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, 19A, 19F, 20, 22F, 23F, and 33F).[23] Immunity is induced primarily through stimulation of B-cells which release IgM[23] without the assistance of T cells.[24]

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 2 years old, presumably due to their less mature immune systems.[23] Non-response is also common amongst older adults.[23] Immunity is not lifelong, so individuals must be re-vaccinated at age 65 if their initial vaccination was given at age 60 or younger.[23] Since no mucosal immunity is provoked, the vaccine does not affect carrier rates, promote herd immunity, or protect against upper or lower respiratory tract infections.[23] Finally, provoking immune responses using unconjugated polysaccharides from the capsules of other bacteria, such as H. influenzae, has proven significantly more difficult.[23]

Conjugated vaccine

The pneumococcal conjugate vaccine consists of capsular polysaccharides covalently bound to the diphtheria toxoid CRM197, which is highly immunogenic but non-toxic.[23] 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.[23] Among other things, this results in mucosal immunity and the eventual establishment of lifelong immunity after several exposures.[23] 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.[25] 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 pneumococcal 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.[26]

There is currently research into producing vaccines than can be given into the nose rather than by injection.[27][28] 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.[29][30] Additional pneumococcal vaccine research is taking place to find a vaccine that offers broad protection against pneumococcal disease.[31]

As of 2017, pneumonia vaccines target up to 23 forms of the bacterium that cause pneumonia with a new version under development covering 72 strains of the bacterium.[32]

References
  1. World Health Organization (April 2012). "Pneumococcal vaccines WHO position paper--2012". Relevé Épidémiologique Hebdomadaire. 87 (14): 129–44. hdl:10665/241904. PMID 24340399. Lay summary (PDF).
  2. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  3. "PneumoADIP website" Archived 2011-02-08 at the Wayback Machine
  4. "Pneumococcal AMC GAVI webpage" Archived 2013-06-07 at the Wayback Machine
  5. "Gavi must stop giving millions in subsidies to Pfizer and GSK for pneumococcal vaccine". Doctors Without Borders - USA. 3 December 2019.
  6. Malhame M, Baker E, Gandhi G, Jones A, Kalpaxis P, Iqbal R, et al. (August 2019). "Shaping markets to benefit global health - A 15-year history and lessons learned from the pentavalent vaccine market". Vaccine. 2: 100033. doi:10.1016/j.jvacx.2019.100033. PMC 6668221. PMID 31384748.
  7. "Pneumococcal Vaccine is Launched in Africa, But Are Donors Getting a Fair Deal from Companies?". Doctors Without Borders - USA.
  8. "Vaccination". Doctors Without Borders - USA.
  9. "Pneumonia vaccine to be part of immunisation drive". The Hindu. Special Correspondent, Special Correspondent. 14 May 2017. ISSN 0971-751X. Retrieved 18 September 2017.CS1 maint: others (link)
  10. "Pneumococcal Vaccination: Information for Health Care Providers". cdc.org. Archived from the original on 23 July 2016. Retrieved 26 July 2016.
  11. "Prevenar — Annex I: Summary of Product Characteristics" (PDF). E.M.E.A. Archived from the original (PDF) on 17 December 2008.
  12. Wilson D (24 February 2010). "Vaccine Approved for Child Infections". The New York Times. Archived from the original on 4 November 2015.
  13. "Prevnar 13". U.S. Food and Drug Administration (FDA). 12 January 2012. STN: 125324. Archived from the original on 18 August 2011.
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  15. "Children to be given new vaccine". BBC News. 8 February 2006. Archived from the original on 30 May 2006.
  16. "Pneumococcal vaccine added to the childhood immunisation programme" (Press release). 8 February 2006. Archived from the original on 23 October 2006.
  17. "Changes to the immunisation programme in the UK". Meningitis Research Foundation. Archived from the original on 13 July 2007. Retrieved 6 May 2017.
  18. "Synflorix, GlaxoSmithKline's pneumococcal vaccine receives European authorisation" (Press release). GlaxoSmithKline. 31 March 2009. Archived from the original on 4 August 2009.
  19. "Critical decline in pneumococcal disease and antibiotic resistance in South Africa". NICD. Archived from the original on 23 July 2015. Retrieved 20 July 2015.
  20. von Gottberg A, de Gouveia L, Tempia S, Quan V, Meiring S, von Mollendorf C, et al. (November 2014). "Effects of vaccination on invasive pneumococcal disease in South Africa". The New England Journal of Medicine. 371 (20): 1889–99. doi:10.1056/NEJMoa1401914. PMID 25386897.
  21. "Pneumococcal vaccine: Canadian Immunization Guide". Government of Canada. 16 February 2020.
  22. "Pinkbook Pneumococcal Epidemiology of Vaccine-Preventable Diseases". CDC. Retrieved 10 December 2017.
  23. 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". International Journal of Antimicrobial Agents. 32 (3): 199–206. doi:10.1016/j.ijantimicag.2008.01.021. PMID 18378430.
  24. Stein KE (June 1992). "Thymus-independent and thymus-dependent responses to polysaccharide antigens". The Journal of Infectious Diseases. 165 Suppl 1 (Suppl 1): S49-52. doi:10.1093/infdis/165-supplement_1-s49. PMID 1588177.
  25. Sniadack DH, Schwartz B, Lipman H, Bogaerts J, Butler JC, Dagan R, et al. (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". The Pediatric Infectious Disease Journal. 14 (6): 503–10. doi:10.1097/00006454-199506000-00007. PMID 7667055.
  26. GAVI Alliance; World Bank. "Saving Lives with New Vaccines: Advance Market Commitments" (PDF).
  27. Hanniffy SB, Carter AT, Hitchin E, Wells JM (January 2007). "Mucosal delivery of a pneumococcal vaccine using Lactococcus lactis affords protection against respiratory infection". The Journal of Infectious Diseases. 195 (2): 185–93. doi:10.1086/509807. PMID 17191163.
  28. Malley R, Lipsitch M, Stack A, Saladino R, Fleisher G, Pelton S, et al. (August 2001). "Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci". Infection and Immunity. 69 (8): 4870–3. doi:10.1128/IAI.69.8.4870-4873.2001. PMC 98576. PMID 11447162.
  29. Burns T, Abadi M, Pirofski LA (August 2005). "Modulation of the lung inflammatory response to serotype 8 pneumococcal infection by a human immunoglobulin m monoclonal antibody to serotype 8 capsular polysaccharide". Infection and Immunity. 73 (8): 4530–8. doi:10.1128/IAI.73.8.4530-4538.2005. PMC 1201218. PMID 16040964.
  30. Fabrizio K, Groner A, Boes M, Pirofski LA (April 2007). "A human monoclonal immunoglobulin M reduces bacteremia and inflammation in a mouse model of systemic pneumococcal infection". Clinical and Vaccine Immunology. 14 (4): 382–90. doi:10.1128/CVI.00374-06. PMC 1865609. PMID 17301214.
  31. "Acute Respiratory Infections (Update September 2009): Streptococcus pneumoniae". Initiative for Vaccine Research (IVR). World Health Organization (WHO). Archived from the original on 23 May 2012.
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Further reading
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