One of the most important immunologic features of the pneumococcus is that protection is afforded by antibodies against its polysaccharide capsule. Each of the ∼100 serotypes of pneumococcus has a different capsule, and antibodies directed against the capsule typically only protect against 1 serotype.1 That is why we continue to need “polyvalent” vaccines to protect against pneumococcus. These vaccines are really many individual vaccines packaged into one vial or syringe.
The first US-licensed pneumococcal vaccine became available in 1977. This vaccine originally contained the polysaccharides from 14 serotypes and was later, in 1983, expanded to contain the polysaccharides from 23 (PPSV23). These vaccines were powerful, but, because they contained polysaccharide only, and are thus T-cell independent, they did not work well in young children, nor did they provide lasting protection. However, covalently binding each polysaccharide to a protein, such as the toxoids of diphtheria or tetanus, made the vaccines more immunogenic and longer lasting, and they worked well even in infants. These became known as pneumococcal conjugate vaccines (PCV).2 In the United States, a PCV that protected against 7 of the most common serotypes, PCV7, was used starting in 2000 and was replaced by PCV13 in 2010. PCV15 and PCV20 are both recommended options for US adults.3 PCV15 is also recommended as an option for protection against pneumococcal disease as part of the routine US childhood series based on its safety, tolerability, and immune responses.4
In this issue of Pediatrics, Banniettis et al describe the safety and tolerability of PCV15 in infants and toddlers.5 Researchers in 10 countries gave ∼2000 children PCV15 and 400 children PCV13 and followed them for adverse events. PCV15 supplies 2 additional serotypes, 22F and 33F, beyond PCV13; these are 2 of the most common current non-PCV13 serotypes. The dosing schedule in the study followed the schedule used in the United States: 2, 4, 6, and 12 to 15 months. PCV15, like PCV13, contains polysaccharides conjugated to a diphtheria toxoid, CRM197, and is adjuvanted with aluminum phosphate. The study revealed that, when infants were given PCV15 with other recommended vaccines, the proportions who had side effects in the 2 weeks after any of the 4 days on which immunizations were administered were similar to the group given PCV13. There were some solicited event types (pain, erythema, decreased appetite, and irritability) that were slightly more common when PCV15 was given, but they were of the same severity. High fevers were rare, and the febrile seizures reported all occurred >3 months after the children received their vaccination and were thus deemed not related to the vaccines. No serious safety concerns were identified. These data and others4 contributed importantly to the decision to license and recommend PCV15 for US children.
Since the introduction of the conjugate vaccines in the United States, the epidemiology of pneumococcal disease has drastically changed. Rates of all invasive pneumococcal disease (IPD) among US children <5 years old decreased by 93% (from 79 to 7 per 100 000 per year) from the years just before PCV introduction until 2019. IPD caused by the 13 serotypes covered by PCV13 decreased by 98% (from 72 to 2 per 100 000 per year) in US children <5 years of age during this same period. In addition, vaccinating US infants has had a significant effect in protecting older adults, via community or “herd” immunity. The rates of IPD in those 65 years and older decreased by 61% (from 61 to 24 per 100 000 per year) for all IPD and by 87% (from 45 to 6 per 100 000 per year) for the types in PCV13.6
PCV20 is now an option in the United States for adults,3 and data are under review for its use in young children. PCVs with even more serotypes are in the early stages of clinical development. It is not clear yet where the limit is on the number of serotypes one can add to a single vaccine and still find the same robust protection and excellent safety profile.
We do not foresee eliminating pneumococcal disease in the United States completely: protection is not 100% against the serotypes in the vaccines, and it is unlikely that the number of serotypes that can go in a single vaccine is limitless. Still, each expansion of serotypes is expected to chip away at the remaining burden of disease.
The pneumococcus is a formidable foe. We currently have safe, well-tolerated, highly accepted, and efficacious vaccines. Still, novel pneumococcal vaccines with expanded serotype coverage are welcome additions to our childhood immunization schedule, when shown to be safe, well tolerated, and immunogenic, as we strive to reduce pneumococcal disease incidence even further.
Drs Campbell and Hammershaimb drafted the commentary and reviewed it critically for important intellectual content; and both authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2022-060428.
FUNDING: No external funding.
CONFLICT OF INTEREST DISCLOSURES: Dr Campbell is an investigator of clinical studies, including vaccine products manufactured and/or sponsored by Merck, Sanofi, GSK, Pfizer, Moderna, Novavax, and Emergent Biosystems. For all studies, funds are provided to his university for the purpose of conducting the trial. Dr Hammershaimb is an investigator of clinical studies including vaccine products manufactured and/or sponsored by Moderna, Novavax, and Emergent Biosystems. For all studies, funds are provided to her university for the purpose of conducting the trial.
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