PCV21-Unique Serotypes Most Prevalent in US Adults With Pneumococcal Disease

Serotypes unique to the pneumococcal 21-valent conjugate vaccine (PCV21, Capvaxive; Merck & Co) are more prevalent among US adults with pneumococcal disease than serotypes unique to the pneumococcal 20-valent conjugate vaccine (PCV20), according to results from a systematic review presented by Merck investigators at IDWeek. The meeting took place from October 19 to October 22, 2025, in Atlanta, GA.¹

Why Is Tracking Pneumococcal Serotypes Important?

Numerous versions of pneumococcal conjugate vaccines have been updated and approved for use since their inception. Most recently, PCV21 was approved and recommended by the Advisory Committee on Immunization Practices (ACIP) for use in eligible adults aged 65 and older and individuals aged 19 to 64 years with certain risk factors for pneumococcal disease. It is indicated for the prevention of pneumonia caused by serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B of Streptococcus pneumoniae.^2,3

Different pneumococcal vaccines protect against some of the same, but also some different, vaccine serotypes compared with other versions. As vaccine serotypes evolve and their circulation in the population shifts in reaction to indirect protection and immunization, reevaluating the included serotypes in PCV21—and their prevalence among adults—is essential. Serotype epidemiology has shifted due to indirect pediatric protection and the emergence of non-vaccine serotypes, complicating efforts to quantify the burden of pneumococcal disease in the US.¹

Investigators from Merck aimed to evaluate the serotype-specific burden of pneumococcal disease based on the unique serotypes included in PCV21 and its predecessor, PCV20. They compared serotypes covered by PCV21 but not PCV20 (9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, 35B) with those covered by PCV20 but not PCV21 (1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F). Through this systematic review, the authors sought to quantify residual PD burden and assess the real-world coverage of PCV21 in adults.^1,2

Which Serotypes Constitute Residual Pneumococcal Burden?

A systematic review of literature published between 2015 and 2025 was initiated. Fifteen full-text US publications, along with CDC Active Bacterial Core (ABC) Surveillance reports, were included. Among these, 13 reported pneumococcal prevalence, 5 reported incidences, 2 reported mortality, 2 reported antimicrobial resistance (AMR), and 1 reported health resource utilization and complications.^1,2

ABC data indicated that PCV20-unique serotypes covered 8.5% of invasive pneumococcal disease (IPD) cases, while PCV21-unique serotypes covered 34.8%. There was a higher pooled prevalence of PCV21-unique serotypes (8.0% to 38.0%) compared with PCV20-unique serotypes (4.4% to 30.5%) in the published studies providing full serotype distribution data, according to the investigators.¹

For adults hospitalized for noninvasive pneumococcal disease between 2009 and 2012, AMR was reported for 7 unique PCV21 serotypes and 1 unique PCV20 serotype. PCV21 non-PCV20 serotypes had a higher resistance to antibiotics often prescribed for non-invasive pneumococcal disease, including penicillin (96% vs 60%) and erythromycin (62% vs 50%), and lower resistance to antibiotics used to treat IPD, like ceftriaxone (9% vs 25%).¹

In adults with invasive and noninvasive pneumonia treated between 2009 and 2017, PCV21-unique serotypes had higher resistance to erythromycin (89% vs 56%) and lower resistance to penicillin (4% vs 33%) and ceftriaxone (5% vs 25%) compared with PCV20-unique serotypes. For serotypes 19F (42%) and 23A (27%), multidrug resistance rates were highest.^1,2

What Should Pharmacists Know?

These results indicate that PCV21-unique serotypes are more prevalent in US adults with pneumococcal disease than those unique to PCV20. The revelation that pneumococcal disease caused by PCV21-unique serotypes could have higher rates of resistance to commonly prescribed antibiotics has major implications for health care professionals. Appropriate treatments should be prescribed for patients with pneumococcal disease based on the serotype impacting them and their resistance to alternative methods.¹

Furthermore, the results shed light on the importance of vaccination with PCV21 for older or at-risk adults. PCV21 specifically protects against key vaccine serotypes that are unique to the formulation and has exhibited broad efficacy across subgroups in numerous clinical trials. Pharmacists can play an important role in disseminating accurate information about the benefits of pneumococcal vaccination, counseling patients on the right vaccine for them, and encouraging others in their community to receive PCV21.^1,4

“To help address the burden of pneumococcal disease, it is important to understand the prevalence and antimicrobial resistance among pneumococcal serotypes,” Paula Annunziato, MD, senior vice president of infectious diseases and vaccines at Merck Research Laboratories, said in a news release. “By covering the serotypes responsible for the majority of invasive pneumococcal disease cases in US adults, based on 2018-2022 national-level CDC data, [PCV21] is specifically designed for adults."²

REFERENCES

1. Martino AM, DeBenedetti L, Nicolae MV, Nellore S, Cossrow N, et al. (P-1425) Burden of pneumococcal disease associated with PCV21 non-PCV20 and PCV20 non-PCV21 serotypes among US adults. Presented: IDWeek; October 19–October 22, 2025; Atlanta, Georgia. Presented October 21, 2025. Accessed Online via IDWeek Virtual Platform November 4, 2025.

2. Systematic review of 15 studies focused on epidemiology and antimicrobial resistance of pneumococcal serotypes covered by CAPVAXIVE (pneumococcal 21-valent conjugate vaccine) in U.S. adults. News release. Merck & Co. Released October 21, 2025. Accessed November 4, 2025. https://www.merck.com/news/systematic-review-of-15-studies-focused-on-epidemiology-and-antimicrobial-resistance-of-pneumococcal-serotypes-covered-by-capvaxive-pneumococcal-21-valent-conjugate-vaccine-in-u-s-adults/

3. Halpern L. ACIP votes to recommend pneumococcal 21-valent conjugate vaccine for adult populations. Pharmacy Times. Published July 2, 2024. Accessed November 4, 2025. https://www.pharmacytimes.com/view/acip-votes-to-recommend-pneumococcal-21-valent-conjugate-vaccine-for-adult-populations

4. Halpern L. Pneumococcal 21-valent conjugate vaccine generates positive response in adults at increased risk of disease. Pharmacy Times. Published October 21, 2024. Accessed November 4, 2025. https://www.pharmacytimes.com/view/pneumococcal-21-valent-conjugate-vaccine-generates-positive-response-in-adults-at-increased-risk-of-disease