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]

Production technique

Prevnar is produced from the seven most prevalent 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.http://www.rxlist.com/cgi/generic/prevnar.htm

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.http://www.slate.com/id/2168854/pagenum/all/

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

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.^[6]

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 age less than 2 years of age.^[7] 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. ^{[8] [9]}

Interestingly, rates of invasive pneumococcal disease among adults has also declined since the introduction of the vaccine.^{[10] [11]} Although, it is more difficult to specifically attribute this decline in adults to the childhood pneumococcal conjugate vaccine since the adult pneumococcal 23-valent polysaccharide vaccine is also available.

While an overall decline in invasive pneumococcal disease is well documented, concerns have been raised regarding a potential increase in the rate of infections caused by serotypes not covered in the vaccine. Recent data suggest that serotype replacement is increasing (1.61- and 1.28-fold increase in children and adults) but remains minimal when compared to the significant reduction observed in the burden of this vaccine-preventable disease.^[12]

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.^[13] Historically 15-20 years pass before a new vaccine reaches one quarter of the population of the developing world.^[14] 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.^[15]

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.^[16]

In addition, Wyeth has been accused of conflict of interest in economic evaluations of Prevnar.^[17]

The selling price of conjugate vaccines is clearly very high ^{[18] [19]}. The WHO, pneumo ADIP and other associations are taking steps to make cheaper, more effective vaccines available with partners in countries such as India, and Brazil.

References and notes

• with followup paper:
  

External links

• Wyeth.com ? Official Wyeth website
• ArabNews.com - 'Pharmaceutical Ads Scare Parents', Lulwa Shalhoub, Arab News (July 4, 2007)
• 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