Pneumococcal conjugate vaccine

Pneumococcal conjugate vaccine or Prevnar is a vaccine used to protect infants and young children against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). Prevnar is a heptavalent vaccine, meaning that it contains the cell membrane sugars of seven serotypes of pneumococcus, conjugated with Diphtheria proteins. It is manufactured by Wyeth as the brand name Prevnar.^[1] In the United States, vaccination with Prevnar is recommended for all children younger than 2 years, and for unvaccinated children between 24 and 59 months old who are at high risk for pneumococcal infections.^[2]

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Production technique

Prevnar is produced from the seven most prevelant strains of Streptococcus pneumoniae bacteria. 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 Corynebacterium diphtheriae strain C7 in a medium of casamino acids and yeast extracts.[1]]

The current 7-valent formulation contains serotypes 4,6B,9V,14,18C,19F, and 23F, and results in a 98% probability of protection against these strains, which caused 80% of the pneumococcal disease in infants. In 2009, Wyeth will be introducing Prevnar 13 which will contain six additional strains (i.e., 1, 3, 5, 6A, 19A and 7F), which will protect children against the majority of the remaining pneumococcal infections.

Centers for Disease Control recommendation

In 2001, the Centers for Disease Control (CDC), upon advice from its Advisory Committee on Immunization Practices, recommended the vaccine be administered to every infant and young child in the US. The resulting demand outstripped production, creating shortages not resolved until 2004. All children, according to current US vaccination schedules, should receive four doses, at two, four, six, and again between twelve and fifteen months of age.

Efficacy

Prevnar is designed to stop seven of about ninety bacteria which cause invasive pneumococcal disease. Each year, IPD kills approximately one million children worldwide.[2]

Since approval, Prevnar's efficacy in preventing invasive pneumococcal disease has been documented by a number of epidemiologic studies.^[3][4][5]

Evidence supporting addition to routine vaccination schedules

According to one study, doctor visits by those who were diagnosed as having chronic ear infections and who took Prevnar dropped about 20 percent, and there was a similar 20 percent reduction in the number of children who needed tube implants to fight the infections, and overall ear infections were reduced by 9 percent.

For US children under the age of two, the chance of being diagnosed with an invasive pneumococcal disease was determined to be about 0.15% per year, or about one case each year for every 670 young children. Pneumococcal meningitis in childhood has been 'associated with' a mortality rate of approximately 1 in 178,571 children. According to data from the product insert,[3] after one dose of the vaccine 0.016% of the recipients (3 out of 18,906) were diagnosed with invasive pneumococcal disease; 0.14% of controls (27 out of 18,910 injected with a different vaccine) got invasive pneumococcal disease. Thus, it was determined Prevnar decreases by 88% a child's relative risk of getting invasive pneumococcal disease. The absolute risk reduction is approximately 0.124%, or 1 fewer diseases each year per 808 young children.

According to a press release from Wyeth, "...a major clinical trial conducted by Kaiser Permanente.suggested that the vaccine is effective against invasive pneumococcal disease caused by seven serotypes (strains) of the bacteria most prevalent among children in the U.S." According to the Harvard Medical School, the Kaiser study was supported by a grant from Wyeth.^{[citation needed]}

According to the Wyeth-funded^{[citation needed]} research, "The study showed that children in the vaccine group fared better than those in the comparison group in other ways. In the primary analysis of all acute otitis media episodes (i.e. earaches), children receiving the investigational 7-valent pnemococcal vaccine (i.e. Prevnar) had 7 percent fewer new episodes."

Clinical study

Prevnar was administered to nearly 20,000 children prior to licensure, and the side effects were evaluated. Rashes at the site of injection were noted in about one percent of children.

Vaccination in the Developing World

Pneumococcal disease is the leading vaccine-preventable killer of young children worldwide, according to the World Health Organization (WHO), killing over 800,000 and up to a million children a year. Ninety percent of these deaths occur in the developing world.^[6] Historically 15-20 years pass before a new vaccine reaches one quarter of the population of the developing world.^[7] Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP) is a GAVI Alliance (GAVI) funded project to accelerate the introduction of pneumococcal vaccinations into the developing world through partnerships between countries, donors, academia, international organizations and industry. With action now, a projected 5.4 million child deaths can be prevented by 2030. In May 2007, 30 of the 72 GAVI countries expressed interest in introducing pneumococcal conjugate vaccine between 2008 and 2010. These countries are Benin, Burundi, the Republic of Congo, Rep. of Cote d'Ivoire, Djibouti, the Democratic Republic of Congo, Ethiopia, Ghana, Guyana, Honduras, Indonesia, Kenya, Madagascar, Malawi, Mali, Mongolia, Nicaragua, Pakistan, Rwanda, Sao Tome and Principe, Senegal, Solomon Islands, Sri Lanka, Sudan, The Gambia, Timor Leste, Togo, Uganda, Yemen, and Zambia.^[8]

Sales

Prevnar is among Wyeth's top revenue producers, with sales in 2005 of $1.5 billion, up 43 percent from 2004.Wyeth Annual report

Controversy

Controversy has arisen regarding pneumococcal vaccine advertisements aired by Wyeth in Poland and Saudi Arabia. A television commercial for Prevnar, showing a dying child and its mother, was banned in Poland by the main pharmaceutical inspector (GIF), Zofia Ulz, on April 3, 2007. According to Ulz, the ad was designed to provoke fear to attract customers. Wyeth responded by asserting the tactic was used to increase awareness of the potential danger represented by pneumococcal infections.[4]

References and notes

• Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen J, Elvin L, Ensor K, Hackell J, Siber G, Malinoski F, Madore D, Chang I, Kohberger R, Watson W, Austrian R, Edwards K (Mar 2000). "Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group.". Pediatr Infect Dis J 19 (3): 187-95. PMID 10749457. with followup paper:
  Black S, Shinefield H (Dec 2002). "Safety and efficacy of the seven-valent pneumococcal conjugate vaccine: evidence from Northern California.". Eur J Pediatr 161 (Suppl 2): S127-31. PMID 12494258.
• Lieu T, Ray G, Black S, Butler J, Klein J, Breiman R, Miller M, Shinefield H (Mar 15 2000). "Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children.". JAMA 283 (11): 1460-8. PMID 10732936.
• Shinefield H, Black S, Ray P, Chang I, Lewis N, Fireman B, Hackell J, Paradiso P, Siber G, Kohberger R, Madore D, Malinowski F, Kimura A, Le C, Landaw I, Aguilar J, Hansen J (Sep 1999). "Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers.". Pediatr Infect Dis J 18 (9): 757-63. PMID 10493334.
• Shinefield H, Black S (Apr 2000). "Efficacy of pneumococcal conjugate vaccines in large scale field trials.". Pediatr Infect Dis J 19 (4): 394-7. PMID 10783042.

• Wyeth.com — Official Wyeth website
• ArabNews.com - 'Pharmaceutical Ads Scare Parents', Lulwa Shalhoub, Arab News (July 4, 2007)
• Chron.com - 'Vaccine tied to "superbug" ear infection', Marilynn Marchione, Associated Press (September 17, 2007)
• NVIC - Statement about Prevnar from the National Vaccine Information Center
• PneumoADIP - Pneumococcal vaccines Accelerated Development and Introduction Plan