The Centers for Disease Control and Prevention (CDC) has updated its recommendations to include the 21-valent pneumococcal conjugate vaccine (PCV21) for use in adults, aiming to provide broader protection against pneumococcal disease. This decision follows a review of clinical trial data demonstrating the vaccine's immunogenicity and safety. The recommendation emphasizes targeted vaccination for adults at increased risk.
Immunogenicity and Efficacy
Clinical trials, including phase II and III randomized controlled trials, have assessed PCV21's immunogenicity compared to existing pneumococcal vaccines such as PCV15, PCV20, and PPSV23. In pneumococcal vaccine-naive adults aged 50 years and older, PCV21 met noninferiority criteria for serotypes shared with comparator vaccines. Notably, PCV21 elicited statistically significantly higher immune responses for most serotypes unique to PCV21, except for serotype 15C, where the immune response was numerically higher compared with PCV20.
In adults aged 50 years and older with prior pneumococcal vaccination (PCV13 or PPSV23), PCV21 showed comparable immunogenicity for shared serotypes and was immunogenic for unique serotypes compared with PPSV23 or PCV15. A study involving adults living with HIV showed similar immunogenicity for shared serotypes and immunogenicity for unique serotypes when comparing PCV21 followed by placebo to PCV15 followed by PPSV23.
Safety Profile
Pooled safety data from four phase III clinical trials, involving both vaccine-naive and vaccine-experienced adults, indicated that PCV21 has a safety profile comparable to that of comparator vaccines (PCV15, PCV20, or PPSV23). The proportion of participants experiencing at least one solicited adverse event was similar between PCV21 (63.3%) and comparator vaccine recipients (63.9%). Injection site pain was the most common solicited injection site event. Among solicited systemic adverse events, fatigue, headache, and myalgia were more common among PCV21 recipients. Most solicited adverse events were mild or moderate.
Impact on Pneumococcal Disease
Before the COVID-19 pandemic, the U.S. saw approximately 100,000 noninvasive pneumococcal pneumonia hospitalizations and 30,000 invasive pneumococcal disease (IPD) cases annually among adults. From 2018 to 2022, serotypes contained in PCV21 caused approximately 80% of IPD cases among adults with indications for vaccination, with 20%–30% due to the eight new serotypes contained in PCV21. The introduction of PCV13 in children reduced disparities in PCV13-type IPD incidence in adults, but racial disparities persist due to non-PCV13 serotypes.
Economic Considerations
Economic models have assessed the cost-effectiveness of PCV21 in various adult populations. Base case estimates of using PCV21 instead of PCV20 for adults currently recommended to receive a PCV ranged from cost-saving to a cost of $58,000 per quality-adjusted life-year (QALY) gained. The cost-effectiveness of PCV21 in adults aged 50–64 years ranged from $3,000 to $270,000 per QALY gained, while use in adults aged 19–49 years was the least economically favorable.
