VAX-31 pneumococcal vaccine meets all Phase 3 endpoints
October 6, 2026
Vaxcyte’s VAX-31 pneumococcal vaccine met all prespecified primary endpoints in OPUS-1, the pivotal Phase 3 trial in adults. The results give the 31-valent conjugate candidate the clinical basis for a Biologics License Application the company plans to file in the first half of 2028. All 28 serotypes VAX-31 shares with Prevnar 20 (PCV20) and/or Capvaxive (PCV21) met the prespecified noninferiority criterion, and the three serotypes unique to VAX-31 plus cross-reactive serotype 20B met superiority. Vaxcyte, based in San Carlos, California and listed on Nasdaq under the ticker PCVX, reported the topline results on October 5, 2026.
What the VAX-31 pneumococcal vaccine showed in adults 50 and older
In the co-primary immunogenicity analysis, all 28 shared serotypes met noninferiority, defined as a lower bound of the 95 percent confidence interval above 0.667 on the opsonophagocytic activity geometric mean ratio. The result held across every category: 11 of 11 serotype comparisons for the 11 serotypes shared by all three vaccines, 9 of 9 for the nine serotypes shared with Prevnar 20 only, and 8 of 8 for the eight serotypes shared with Capvaxive only. The three serotypes unique to VAX-31 and cross-reactive serotype 20B met the superiority criterion of a lower bound above 2.0, with prespecified multiplicity adjustment.
Immunobridging and individual comparisons
For the prespecified primary immunobridging endpoint, VAX-31 met the 0.667 noninferiority threshold for all 321 serotype comparisons in adults aged 18 to 49 relative to adults aged 50 to 64. In the prespecified individual comparator analyses, the vaccine met noninferiority for 20 of 20 serotypes shared with Prevnar 20 and 17 of 19 shared with Capvaxive. Serotypes 3 and 12F missed the stricter criterion and met the historical threshold above 0.5, which was a prespecified key secondary endpoint.
Trial design
OPUS-1 is a randomized, double-blind, active-controlled Phase 3 trial in healthy, pneumococcal-naive U.S. adults. It enrolled 3,572 adults aged 50 and older plus a separate cohort of 475 adults aged 18 to 49, dosing 4,047 participants at approximately 30 sites across the United States. Adults 50 and older were randomized 1:1:1 to a single dose of VAX-31, Prevnar 20 or Capvaxive; those aged 18 to 49 were randomized 3:1 to VAX-31 or Prevnar 20, which served as the safety comparator. In the High Dose formulation being tested in the OPUS program, every serotype is dosed at 3.3 mcg except serotypes 1, 5 and 22F, which are dosed at 4.4 mcg. Immune responses were measured one month after vaccination, and safety and tolerability are assessed for six months. The trial is registered at ClinicalTrials.gov under NCT07284654.
The coverage case for a 31-valent vaccine
VAX-31 is designed to cover approximately 95 percent of invasive pneumococcal disease and approximately 88 percent of pneumococcal pneumonia circulating in U.S. adults aged 50 and older. Vaxcyte estimates that the additional serotypes amount to an incremental 13 to 36 percent of IPD coverage and 19 to 31 percent of pneumococcal pneumonia coverage over current standard-of-care adult conjugate vaccines. In U.S. children under five, the vaccine is designed to cover approximately 91 percent of IPD and approximately 96 percent of acute otitis media, which the company estimates would add 27 to 47 percent of IPD coverage and 35 to 62 percent of otitis media coverage over the infant vaccines now in use.
The disease burden behind the numbers
Pneumococcal pneumonia is estimated to cause approximately 225,000 adult hospitalizations in the United States each year. The World Health Organization lists Streptococcus pneumoniae among the antibiotic-resistant pathogens that need urgent action, and the CDC calls drug-resistant Streptococcus pneumoniae a “serious threat.” In children under five the bacterium is the leading cause of vaccine-preventable deaths worldwide, and pneumococci cause more than 50 percent of bacterial meningitis cases in the United States. Pneumonia vaccine access is uneven, particularly in lower-middle-income countries, and broader coverage will only reach patients if adult immunization programmes can deliver it.
Pipeline and platform
VAX-31 uses Vaxcyte’s site-specific, carrier-sparing conjugation technology and is produced with XpressCF, a cell-free protein synthesis platform licensed exclusively from Sutro Biopharma. The pipeline also includes VAX-24, a 24-valent conjugate candidate with positive Phase 2 results in adults and infants; VAX-XL in earlier-stage development; VAX-A1 for Group A Strep, in a Phase 1 study in adults; and VAX-GI, designed to prevent Shigella. In May 2025, the FDA expanded the Breakthrough Therapy designation for VAX-31 to include prevention of pneumonia caused by Streptococcus pneumoniae in addition to prevention of invasive pneumococcal disease in adults.
What comes next
Vaxcyte expects safety, tolerability and immunogenicity data from the OPUS-2 and OPUS-3 Phase 3 trials in the first half of 2027, followed by a manufacturing consistency study and the planned BLA submission in the first half of 2028. Topline results from the VAX-31 infant Phase 2 randomized, dose-finding study, covering both the three-dose primary series and the booster dose, are expected by the end of the first half of 2027. The company hosted a webcast and conference call on October 5, 2026 at 8:00 a.m. ET, and the archived event stays on its investor relations site for 30 days.
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