Pneumococcal conjugate vaccine

Vaccine against Strep pneumoniae

Pneumococcal conjugate vaccine is a pneumococcal vaccine made with the conjugate vaccine method and used to protect infants, young children, and adults against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). It contains purified capsular polysaccharide of pneumococcal serotypes conjugated to a carrier protein to improve antibody response compared to the pneumococcal polysaccharide vaccine. The World Health Organization (WHO) recommends the use of the conjugate vaccine in routine immunizations given to children. Vaccine mediated immunity is "conferred mainly by opsonophagocytic killing of S. pneumoniae." The most common side effects in children are decreased appetite, fever (only very common in children aged six weeks to five years), irritability, reactions at the site of injection (reddening or hardening of the skin, swelling, pain or tenderness), somnolence (sleepiness) and poor quality sleep.

Prevnar 20 (PCV20) is the third version of a vaccine produced by the Wyeth subsidiary of Pfizer. In April 2023, the FDA approved Prevnar 20 for the prevention of invasive disease caused by the 20 different serotypes of S. pneumoniae contained in the vaccine for individuals 6 weeks through 17 years of age; and for the prevention of otitis media (ear infection) caused by 7 of the serotypes of Streptococcus pneumoniae contained in the vaccine for children 6 weeks through 5 years of age. In June 2023, the Advisory Committee on Immunization Practices (ACIP) approved PCV20 (Prevnar 20) for use in US children. The second version, Prevnar 13 (PCV13), contained thirteen serotypes of pneumococcus (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). It replaced Prevnar, the pneumococcal heptavalent conjugate vaccine (PCV7). Prevnar 13 was approved for use in the European Union in December 2009. In February 2010, Prevnar 13 was approved in the United States to replace Prevnar. After waiting for the outcome of a trial underway in the Netherlands, the Centers for Disease Control and Prevention (CDC) recommended the vaccine for adults over age 65 in August 2014. The first version, the heptavalent Prevnar (PCV7), was produced from the seven most prevalent strains of Streptococcus pneumoniae bacteria in the U. S. (4, 6B, 9V, 14, 18C, 19F, and 23F). Prevnar was approved for use in the United States in February 2000, and vaccination with Prevnar was recommended for all children younger than 2 years and for unvaccinated children between 24 and 59 months old who were at high risk for pneumococcal infections. The formulation resulted in a 98% probability of protection against the constituent strains, which caused 80% of the pneumococcal disease in infants in the U. S. PCV7 is no longer produced. In the Prevnar vaccines, the bacterial cell capsule sugars, a characteristic of these pathogens, are linked (conjugated) through reductive amination to CRM197, a nontoxic recombinant variant of diphtheria toxin. CRM197 is derived from the C7 strain of Corynebacterium diphtheriae grown in a medium of casamino acids and yeast extracts. Bacteria bearing the vaccine's polysaccharide sugars are grown separately in soy peptone broths. The resulting glycoconjugate and GSK received European Commission authorization to market Synflorix in March 2009.

Vaxneuvance is a pneumococcal 15 valent conjugate vaccine created by Merck that was approved for medical use in the United States in July 2021. The vaccine was developed under the code name "V114". It is identical to PCV13, except that it adds serotypes 22F and 33F. These two serotypes are particularly important because, after "widespread use of the PCV13 [vaccine] in many countries," these two serotypes are now "among leading serotypes causing IPD in children and adults." On 14 October 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vaxneuvance, intended for prophylaxis against pneumococcal pneumonia and associated invasive disease. Vaxneuvance was approved for medical use in the European Union in December 2021.

As with all immunizations, whether it is available or required, and under what circumstances, varies according to the decisions made by local public health agencies. Children under the age of two years fail to mount an adequate response to the 23 valent adult vaccine, and so a pneumococcal conjugate vaccine is used. While this covers only seven strains out of more than ninety strains, these seven strains cause 80% to 90% of cases of severe pneumococcal disease, and it is considered to be nearly 100% effective against these strains.

In 2001, the Centers for Disease Control and Prevention (CDC), upon advice from its Advisory Committee on Immunization Practices (ACIP), recommended the vaccine be administered to every infant and young child in the United States. The resulting demand outstripped production, creating shortages not resolved until 2004. All children, according to the U. S. vaccination schedule, should receive four doses, at two months, four months, six months, and again between one year and fifteen months of age. The CDC updated the pneumococcal vaccine guidelines for adults 65 years of age or older in 2019. In October 2021, the CDC recommended that adults 65 years of age or older who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown should receive a pneumococcal conjugate vaccine (either PCV20 or PCV15). The CDC recommended that adults aged 19 to 64 years with certain underlying medical conditions or other risk factors who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown should receive a pneumococcal conjugate vaccine (either PCV20 or PCV15).]] Prevnar 7 is designed to stop seven of about ninety pneumococcal serotypes which have the potential to cause invasive pneumococcal disease (IPD). In 2010, a 13 valent vaccine was introduced. Each year, IPD kills approximately one million children worldwide. Since approval, Prevnar's efficacy in preventing IPD has been documented by a number of epidemiologic studies. There is evidence that other people in the same household as a vaccinee also become relatively protected. There is evidence that routine childhood vaccination reduces the burden of pneumococcal disease in adults and especially high risk adults, such as those living with HIV/AIDS. 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.

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.

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 of less than two years of age. Rates of invasive pneumococcal disease among adults have also declined since the introduction of the vaccine. Approximately ninety percent of these deaths occur in the developing world. Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP) was a GAVI Alliance (GAVI) funded project to accelerate the introduction of pneumococcal vaccinations into low income countries through partnerships between countries, donors, academia, international organizations and industry. GAVI continues this work and as of March 2013, 25 GAVI eligible and supported countries have introduced the pneumococcal conjugate vaccine. Further, 15 additional GAVI countries have plans to introduce the vaccine into their national immunization program and 23 additional countries have approved GAVI support to introduce the vaccine.

On 16 December 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Apexxnar, intended for prophylaxis against pneumococcal pneumonia and associated invasive disease. Apexxnar was approved for medical use in the European Union in February 2022.

Prevnar 13 is Pfizer's best selling product. It had annual sales of billion in 2020.

Merck is investigating a 21 valent vaccine (code named V116) against pneumococcus serotypes.