Issue: March 2019
March 21, 2019
2 min read

Would it be more beneficial to promote a pneumococcal vaccine that includes all or most serotypes to prevent disease or a ‘custom’ vaccine based on serotype prevalence?

Issue: March 2019
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Click here to read the Cover Story, “PCV13 vaccination highly effective but complicated by serotype replacement”.


The vaccine that is needed to prevent pneumococcal disease should include proteins that are conserved in all or nearly all pneumococci. It is just that simple.

The vaccine that is needed to prevent pneumococcal disease should include proteins that are present in all or nearly all pneumococci. The best option might be to alter pneumolysin so that it retains its ability to immunize but no longer acts as a toxin.

Daniel M. Musher, MD
Daniel M. Musher

Years ago, I specifically suggested to the research directors of several pharmaceutical companies that they consider this type of altered pneumococcal protein, because they were working on vaccines that conjugated capsular polysaccharide to a protein. They refused. They said that they had already studied an altered diphtheria toxin, and that was what they wanted to use.

Much more research needs to be done on this topic. Only a few groups in the world are doing this kind of research. Studies have been conducted at the University of Alabama at Birmingham and in Australia.

Moving forward, this type of vaccine would require more interest and funding.

Daniel M. Musher, MD, is a distinguished service professor of medicine at Baylor College of Medicine. Disclosure: Musher reports no relevant financial disclosures.



Prevention of all pneumococcal diseases would be great, but in a hypothetical scenario where all pneumococcal colonization is eliminated, pneumococcal diseases might be replaced by other diseases caused by pathogens that may take over the nasopharyngeal niche left by the pneumococcus.

Previous experience in the United States with existing PCVs can be informative. These vaccines were designed to cover the most common serotypes that caused invasive pneumococcal disease among children. The vaccines proved very effective in preventing pneumococcal diseases, and they also removed the vaccine serotypes from the children’s nasopharynx, the natural reservoir of the bacteria. Other nonvaccine pneumococcal serotypes moved into that nasopharyngeal niche and replaced serotypes that were eliminated by the vaccine.

Carlos G. Grijalva, MD, MPH
Carlos G. Grijalva

Although some serotypes that replaced vaccine serotypes, such as 19A, were invasive and became common causes of residual disease after introduction of the seven-valent conjugate vaccine, the levels of pneumococcal disease — regardless of serotype — have remained substantially and consistently lower than what they were before vaccine introduction.

Similarly, after switching from PCV7 to PCV13, other serotypes that were not covered by PCV13 started colonizing the nasopharynx of vaccinated children. Pneumococcal diseases declined further after transition to PCV13, and now most of the residual disease is caused by other serotypes not covered by PCV13. In many ways, this is occurring because the new “replacement” serotypes appear to be less pathogenic than the ones that were removed through vaccination, but it is difficult to know what would happen when other serotypes are removed, something that would need to be discussed with the use of higher valency vaccines.

It could be that the new replacement serotypes are less pathogenic, and so pneumococcal disease continues declining. Alternatively, it could be that some of the new replacement serotypes may be more pathogenic and those may become important causes of replacement disease.

It is also challenging to know what would happen if all pneumococcal serotypes were removed with a new hypothetical vaccine that would cover all serotypes. Prevention of all pneumococcal diseases would be great, but could pneumococcal diseases be replaced by other diseases caused by pathogens that may take over the nasopharyngeal niche left by the pneumococcus? It is important to consider the potential unintended consequences of future decisions.

Carlos G. Grijalva, MD, MPH, is an associate professor in the division of pharmacoepidemiology, department of health policy, at Vanderbilt University Medical Center. Disclosure: Grijalva reports receiving consulting fees from Pfizer, Sanofi-Pasteur and Merck and research support from Sanofi-Pasteur, Campbell Alliance, CDC, NIH, FDA and the Agency for Healthcare Research & Quality.