The co-primary immunogenicity end points were grouped by serotype overlap. Noninferiority, defined as a lower bound of the 95% CI for the opsonophagocytic activity (OPA) geometric mean ratio above 0.667, was assessed for the 11 serotypes shared by all 3 vaccines, the 9 shared only with PCV20, and the 8 shared only with PCV21. Superiority (lower bound above 2.0) was assessed for the 3 serotypes unique to VAX-31 and cross-reactive serotype 20B. Safety is being evaluated through 6 months after vaccination.1
Topline Results Meet Primary End Points
In adults aged 50 years and older, all 28 serotypes shared with PCV20 and/or PCV21 met the noninferiority criterion, and all 4 unique and cross-reactive serotypes met the superiority criterion. All 32 immunobridging comparisons between adults aged 18 to 49 years and those aged 50 to 64 years also met noninferiority.2
In prespecified individual comparisons, VAX-31 met noninferiority for 20 of 20 serotypes shared with PCV20 and 17 of 19 shared with PCV21. Serotypes 3 and 12F missed the 0.667 threshold against PCV21 but met the historical threshold of 0.5. Solicited reactions were generally mild to moderate, most resolved within 48 hours, and no serious adverse events were considered vaccine-related.2
James Wassil, MS, MBA, chief scientific officer and chief operating officer of Vaxcyte and the poster’s presenting author, said he expects the comparison with PCV21 “to be a particular focus of FDA review,” given that serotypes unique to PCV21 account for a larger share of adult disease in the United States.1,2
OPUS-2 and OPUS-3 Address Co-Administration and Prior Vaccination
OPUS-2 (NCT07365826) is a randomized, placebo-controlled, descriptive trial in 1390 pneumococcal-naive adults aged 50 years and older. Participants received VAX-31 with a seasonal influenza vaccine on day 1, followed by a placebo at month 1, or a placebo with the influenza vaccine followed by VAX-31 at month 1. Primary end points compare OPA responses to VAX-31 and hemagglutination inhibition responses to the influenza vaccine with and without co-administration.1
OPUS-3 (NCT07425392) enrolled 752 adults aged 50 years and older who previously received a licensed pneumococcal vaccine, including PPSV23 or PCV20. Participants were randomly assigned 3:1 to VAX-31 or PCV20, at least 1 year after a prior PCV or PPSV23, or at least 6 months after PCV21. The primary objective is to assess serotype-specific OPA responses across all 31 serotypes and serotype 20B.1
Implications for Pharmacists
The CDC currently recommends a PCV for all adults aged 50 years and older, with PCV15, PCV20, or PCV21 as options; after PCV20 or PCV21, additional vaccination is not recommended. VAX-31 remains investigational. Results from OPUS-2 and OPUS-3 are expected in the first half of 2027, and Vaxcyte plans to submit a Biologics License Application in the first half of 2028. Together, the trials will provide data on coadministration with influenza vaccine and on use in previously vaccinated adults, both relevant to how a future vaccine could be incorporated into adult immunization practice.1,2,4
The trials were funded by Vaxcyte, and the poster authors are current or former employees of the company. The OPUS-1 findings are topline results and have not yet been published in a peer-reviewed journal.1,2
REFERENCES1. Wassil J, Fairman J, Jiang Q, Migone TS, Lamola S, Sisti M. Design and rationale of the phase 3 OPUS-1, OPUS-2, and OPUS-3 trials evaluating a 31-valent pneumococcal conjugate vaccine (VAX-31) in adults. Poster P-223. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC.2. Vaxcyte reports positive topline data from OPUS-1, the pivotal adult phase 3 trial of VAX-31, the company’s 31-valent pneumococcal conjugate vaccine candidate. News release. Vaxcyte, Inc. October 5, 2026. Accessed October 29, 2026. https://investors.vaxcyte.com/news-releases/news-release-details/vaxcyte-reports-positive-topline-data-opus-1-pivotal-adult-phase3. Wassil J, Fairman J, Fierro C, et al. Safety, tolerability, and immunogenicity of a 31-valent pneumococcal conjugate vaccine (VAX-31) in healthy adults aged 50 years and older from the USA: a phase 1/2 1/2, double-blinded, active-controlled, parallel-group, dose-finding randomized clinical trial. Lancet Infect Dis. 2026;26(7):739-750.4. Pneumococcal vaccine recommendations. CDC. February 25, 2026. Accessed October 29, 2026. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html