Vaxcyte’s VAX-31 Pneumococcal Vaccine Meets All Phase 3 Primary Goals

Vaxcyte’s 31-valent pneumococcal conjugate vaccine (PCV31) candidate, VAX-31, met all prespecified primary endpoints in the phase 3 OPUS-1 trial, according to a release.¹ The vaccine produced noninferior immune responses for all 28 serotypes it shares with Prevnar 20 (PCV20) and/or Capvaxive (PCV21), as well as superior responses for the 3 serotypes only it covers.

“We believe these positive OPUS-1 results provide clinical validation of our site-specific, carrier-sparing platform’s potential to deliver broader-spectrum pneumococcal vaccines while maintaining the magnitude of immune responses,” said Grant Pickering, CEO and co-founder of Vaxcyte, according to the release. “VAX-31 met all prespecified primary immunogenicity endpoints across all age groups studied in this pivotal phase 3 trial, providing the clinical cornerstone for our planned Biologics License Application (BLA).”

The pivotal OPUS-1 trial enrolled 4047 adults across roughly 30 sites in the US, evaluating a high-dose formulation containing 3.3 micrograms of most serotypes and 4.4 micrograms for serotypes 1, 5, and 22F. Safety data demonstrated that VAX-31 was well tolerated and had a safety profile comparable with PCV20 and PCV21, featuring mostly mild or moderate local and systemic reactions that typically resolved within 48 hours.^1,2

READ MORE: The Uncounted Threat: Antibiotic-Resistant Pneumonia

Meanwhile, Vaxcyte completed enrollment in the phase 3 OPUS-2 trial, evaluating concomitant administration of VAX-31 with a seasonal influenza vaccine in 1300 adults to support real-world clinical application.²

Clinical Findings and Immunogenicity Standards

In adults aged 50 and older, VAX-31 achieved statistical noninferiority for all 28 serotypes shared with PCV20 or PCV21 under a stringent noninferiority threshold where the lower bound of the 95% confidence interval exceeded 0.667. Furthermore, the vaccine demonstrated statistical superiority for its 3 unique serotypes 2, 7C, and 20C, as well as the cross-reactive serotype 20B.¹

The trial also satisfied its primary immunobridging endpoint across all 32 serotype comparisons when evaluating younger adults aged 18 to 49 against adults aged 50 to 64. In individual comparator analyses, VAX-31 matched PCV20 on 20 out of 20 shared serotypes and PCV21 on 17 of 19 shared serotypes at the 0.667 threshold, while meeting historical noninferiority thresholds for the remaining 2 serotypes 3 and 12F. These immunogenicity benchmarks are critical for overcoming carrier suppression, a phenomenon where adding capsular antigens can diminish antibody responses in traditional conjugate platforms.^1-3

Current adult vaccines present clinical trade-offs because PCV20 maintains coverage of historically prevalent strains like serotypes 4 and 19F, while PCV21 focuses on strains that dominate recent adult invasive pneumococcal disease (IPD). VAX-31 bridges this gap by combining coverage of circulating and historical strains into a single formulation, targeting serotypes responsible for roughly 86.7% of adult nonbacteremic pneumonia and 93.9% of adult IPD.^1,3

Modeling studies demonstrate that PCV31 holds the potential to prevent the highest annual burden of pneumococcal disease among pipeline candidates, offering vital relief against a pathogen responsible for 225,000 adult pneumonia hospitalizations annually in the US. Vaxcyte plans to report additional data from the OPUS-2 and OPUS-3 trials in the first half of 2027 to prepare for a planned BLA submission in 2028.^1-3

Pipeline Landscape and Implications for Pharmacy Practice

The broader pneumococcal vaccine landscape is also advancing rapidly in pediatric care, where serotype replacement and persistent pathogens continue to challenge public health. Pfizer recently reported phase 2 data for its 25-valent pediatric vaccine candidate, PCV25, which generated a 15-fold increase in serotype 3 antibody titers relative with Prevnar 20 in infants.^3,4

Serotype 3 features a thick capsular membrane and mucoid characteristics that have historically blunted vaccine responses, making enhanced immunogenicity essential for preventing pediatric pneumonia and empyema. Despite PCV25 projected to cover up to 90% of pediatric invasive strains, broader multi-valent platforms like PCV31 are being evaluated to address mucosal disease burdens such as acute otitis media.^2-4

As higher-valency candidates move through clinical trials toward commercial availability, community and clinical pharmacists will play a pivotal role in operationalizing new immunization strategies.⁴

Pharmacists remain central drivers of vaccine uptake by utilizing electronic health record prompts, conducting routine immunization screenings, and educating patients on evolving Advisory Committee on Immunization Practices (ACIP) guidelines. Federal policy updates shifting toward shared clinical decision-making frameworks highlight the need for pharmacists to understand complex serotype coverage profiles and administration schedules.

By maintaining awareness of clinical data from trials like OPUS-1, pharmacists can effectively counsel patients, clarify vaccine options, and protect communities against disease.⁴

“We believe VAX-31’s combination of broader coverage and robust immune responses, demonstrated in a trial inaugurating a more stringent noninferiority standard, sets a new benchmark for the class and gives us confidence in its potential for approval,” concluded Pickering.¹ “We look forward to announcing results from OPUS-2 and OPUS-3 in the first half of 2027, to be followed by a manufacturing consistency study, as we work toward making this vaccine broadly available to help protect adults from the consequences of pneumococcal disease.”

READ MORE: Pneumococcal Resource Center

REFERENCES

1. 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. Vaxcyte. News Release. October 5, 2026. Accessed November 11, 2026. https://investors.vaxcyte.com/news-releases/news-release-details/vaxcyte-reports-positive-topline-data-opus-1-pivotal-adult-phase

2. Vaxcyte completes enrollment of OPUS-1 and OPUS-2 phase 3 trials evaluating VAX-31 for the prevention of invasive pneumococcal disease and pneumonia in adults. Vaxcyte. News Release. March 23, 2026. Accessed November 11, 2026. https://www.barchart.com/press-releases/896310/vaxcyte-completes-enrollment-of-opus-1-and-opus-2-phase-3-trials-evaluating-vax-31-for-the-prevention-of-invasive-pneumococcal-disease-and-pneumonia-in-adults

3. King LM, Andrejko KL, Kobayashi M, et al. Pneumococcal serotype distribution and coverage of existing and pipeline pneumococcal vaccines. J Infect Dis. 2025;232(4):e609-e620. doi:10.1093/infdis/jiaf376

4. Nowosielski B. Pfizer reports strong phase 2 data for 25-valent pediatric PCV. Drug Topics. October 30, 2026. Accessed November 11, 2026. https://www.drugtopics.com/view/pfizer-reports-strong-phase-2-data-for-25-valent-pediatric-pcv