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Pneumococcal vaccine

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Pneumococcal vaccines are specialized subunit vaccines designed to protect humans against the bacterium Streptococcus pneumoniae. This bacterium is responsible for several serious medical conditions, including pneumonia, meningitis, and sepsis. Because these diseases can be life-threatening, vaccines are a vital tool in global public health. There are two primary categories of these vaccines: polysaccharide vaccines and conjugate vaccines. These are administered via injection into either a muscle or the area just under the skin. The World Health Organization (WHO) specifically recommends conjugate vaccines for routine childhood immunizations, including for children living with HIV/AIDS.

Prevenar13 Suspension Liquid for Injection
Prevenar13 Suspension Liquid for Injection

To understand how these vaccines function, we must look at how they interact with the immune system. Polysaccharide vaccines consist of purified polysaccharides from 23 different serotypes, which are specific strains of the bacteria. These vaccines work by stimulating B-cells to release IgM antibodies. However, this process does not involve T cells, making the immune response less robust. Because they do not provoke mucosal immunity, they do not reduce how many people carry the bacteria or protect the respiratory tract. This lack of a strong response is why polysaccharide vaccines are ineffective in children under two years old or in people with poor immune function.

Conjugate vaccines, or PCVs, use a different and more complex mechanism to build immunity. These vaccines consist of capsular polysaccharides that are covalently bound to a protein called CRM197. This protein is highly immunogenic, meaning it triggers a strong response, but it is non-toxic to the patient. By attaching the sugar coating of the bacteria to this protein, the vaccine recruits CRM197-specific type 2 helper T cells. This recruitment allows the body to undergo immunoglobulin type switching to produce more than just IgM. Crucially, this process creates memory B cells, which leads to mucosal immunity and long-lasting, lifelong protection after several exposures.

The development of these vaccines has spanned over a century of scientific discovery. Researchers began characterizing the different subtypes of pneumococcus in the early 1900s. The first polysaccharide vaccine, which was tetravalent, was developed in 1945. By the 1980s, scientists had developed the 23-valent polysaccharide vaccine. The first conjugate vaccine, a heptavalent version, reached the market in the year 2000. Since then, new versions have been released to cover more serotypes and combat antibiotic-resistant strains. For example, the 13-valent conjugate vaccine (PCV13) was introduced in 2010, and the 20-valent version (PCV20) was approved in 2021.

share of one year olds who received the final dose of pneumococcal vaccine, World, 2024 (cropped)
share of one year olds who received the final dose of pneumococcal vaccine, World, 2024 (cropped)

Vaccination efforts have produced significant, measurable results in public health statistics. In South Africa, the introduction of PCV7 and PCV13 led to a massive decline in invasive pneumococcal disease (IPD). Among children under two, the overall incidence of IPD fell by nearly 70%. Furthermore, the rates of IPD caused by bacteria specifically targeted by the vaccine dropped by nearly 90%. The conjugate vaccine itself is highly effective, showing a 71% to 93% success rate in preventing severe disease when three or four doses are given. The 23-valent polysaccharide vaccine also shows high protective efficacy, ranging from 76% to 92% for the 23 most prevalent types.

Global health organizations use various strategies to ensure these vaccines reach those in need. The PneumoADIP program works to accelerate the evaluation and access to new vaccines in the developing world. This program is funded by the Global Alliance for Vaccines and Immunization (GAVI). To address the lack of affordable vaccines, GAVI launched a pilot Advance Market Commitment (AMC) in June 2009. Under an AMC, donors provide a legally binding guarantee to purchase a set amount of vaccines at an agreed price if they meet safety standards. This strategy aims to create a guaranteed market for manufacturers while ensuring affordability for developing nations. The AMC was estimated to prevent more than 1.5 million childhood deaths by 2020.

However, the implementation of these programs has faced some criticism and complexity. Doctors Without Borders has argued that the AMC model might not encourage enough innovation or competition. They noted that the system allowed a duopoly between Pfizer and GlaxoSmithKline, which made it harder for cheaper options, like those from the Serum Institute of India, to enter the market. This resulted in price discrimination, where middle-income countries faced prices about ten times higher than those paid by GAVI-supported nations. Despite these challenges, the vaccines remain essential. The conjugate vaccine's ability to reduce colonization rates also provides herd immunity, protecting even those who are not vaccinated by breaking the chain of transmission.

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