VAX-31 Meets Primary Endpoints in Phase 3 Pneumococcal Vaccine Study

The VAX-31 pneumococcal conjugate vaccine (PCV) candidate met all prespecified primary endpoints in OPUS-1, the pivotal adult phase 3 trial, according to the vaccine’s manufacturer, Vaxcyte.¹ The 31-valent vaccine was compared with Prevnar 20 (20-valent PCV; Pfizer), or PCV20, and Capvaxive (21-valent PCV; Merck), or PCV21. OPUS-1 results will anchor a planned Biologics License Application (BLA) to the US Food and Drug Administration (FDA).¹

Current adult PCVs differ in serotype coverage. This forces a tradeoff between serotypes now driving disease and historically important ones. Vaxcyte estimates VAX-31 could cover approximately 95% of invasive pneumococcal disease (IPD) and 88% of pneumococcal pneumonia in US adults 50 and older.¹

Those figures represent an incremental 13% to 36% of IPD coverage and 19% to 31% of pneumonia coverage over available adult PCVs.¹ In May 2025, the FDA expanded breakthrough therapy designation for VAX-31 to include pneumococcal pneumonia in addition to IPD.¹

Phase 3 Data

OPUS-1 (NCT07284654) is a randomized, double-blind, active-controlled trial of healthy, pneumococcal-naive US adults at approximately 30 sites.¹ Participants 50 and older (n = 3,572) were randomized 1:1:1 to a single dose of VAX-31, PCV20, or PCV21. Adults aged 18 to 49 years (n = 475) were randomized 3:1 to VAX-31 or PCV20.¹

Investigators measured immune responses as opsonophagocytic activity (OPA) geometric mean ratios (GMRs) one month after vaccination. Safety follow-up continues for six months.¹ In adults 50 and older, all 28 serotypes shared with PCV20 and/or PCV21 met the noninferiority criterion, defined as a lower bound of the 95% CI (LBCI) above 0.667.¹

The three serotypes unique to VAX-31 and one cross-reactive serotype met the superiority criterion (LBCI >2.0).¹ In the immunobridging analysis, VAX-31 met noninferiority across all 32 serotype comparisons in adults 18 to 49 vs adults 50 to 64.¹ In individual comparator analyses, VAX-31 met the 0.667 threshold for 20 of 20 serotypes shared with PCV20 and 17 of 19 shared with PCV21.

VAX-31 was well tolerated, with a safety profile similar to PCV20 and PCV21 across all ages studied.¹ Solicited local and systemic reactions through day 7 were generally mild to moderate, and most resolved within 48 hours. No serious adverse events were considered vaccine related, and no participants discontinued because of adverse events.¹

James Wassil, chief scientific officer and chief operating officer of Vaxcyte, said the company expects FDA review to focus on the PCV21 comparison. Serotypes unique to PCV21 account for a larger share of current US adult disease.¹ He added PCV20 remains an important comparator for serotypes 4 and 19F, which PCV21 does not contain.¹

About the Vaccine

VAX-31 contains capsular polysaccharides from 31 Streptococcus pneumoniae serotypes: 1, 2, 3, 4, 5, 6A, 6B, 7C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 16F, 17F, 18C, 19A, 19F, 20B, 22F, 23A, 23B, 23F, 31, 33F, and 35B.² Each polysaccharide is individually conjugated to eCRM, a proprietary nontoxic diphtheria carrier protein based on the CRM197 sequence.²˒³

Vaxcyte produces eCRM with XpressCF, a cell-free protein synthesis platform licensed from Sutro Biopharma.¹ The protein carries multiple insertions of the non-native amino acid para-azidomethyl-L-phenylalanine (pAMF), and polysaccharides attach at these defined sites via copper-free click chemistry.³ This site-specific, carrier-sparing approach is designed to improve process consistency and allow more serotypes without promoting carrier suppression.³

The adult high dose formulation used in the OPUS program delivers 3.3 mcg of polysaccharide per serotype, except serotypes 1, 5, and 22F at 4.4 mcg.¹ In the earlier phase 1/2 study, VAX-31 was supplied as a preservative-free 0.5-mL intramuscular dose in single-use glass vials. The high dose contained approximately 90 mcg of eCRM and required refrigerated storage at 2 °C to 8 °C.²

Vaxcyte's earlier conjugate formulations, including VAX-24 and a preclinical 31-valent prototype, mix the conjugates with an aluminum phosphate adjuvant.³˒⁴ The company has not publicly released a full excipient list for the phase 3 formulation.

"Important gaps remain in adult pneumococcal disease coverage," Luis Jodar, PhD, chief medical officer of Vaxcyte, said in the announcement.¹ He noted VAX-31 is designed to cover both currently circulating and historically important serotypes in a single vaccine.¹

Vaxcyte expects OPUS-2 and OPUS-3 results in the first half of 2027, followed by a manufacturing consistency study. The company plans to submit the BLA in the first half of 2028.¹ It also expects topline data from the VAX-31 infant phase 2 dose-finding study by the end of the first half of 2027.¹

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. News release. Vaxcyte, Inc. October 5, 2026. Accessed October 7, 2026. https://investors.vaxcyte.com/news-releases/news-release-details/vaxcyte-reports-positive-topline-data-opus-1-pivotal-adult-phase

2. Safety, tolerability, and immunogenicity study of a 31-valent pneumococcal conjugate vaccine (VAX-31) in adults. Study protocol. ClinicalTrials.gov identifier: NCT06151288. Accessed October 7, 2026. https://cdn.clinicaltrials.gov/large-docs/88/NCT06151288/Prot_000.pdf

3. Development of a next generation 30+ valent pneumococcal conjugate vaccine (VAX-XP) using site-specific carrier protein conjugation. Open Forum Infect Dis. 2021;8(suppl 1). doi:10.1093/ofid/ofab466.1241

4. Safety, tolerability, and immunogenicity study of a 24-valent pneumococcal conjugate vaccine (VAX-24) in adults. Study protocol. ClinicalTrials.gov identifier: NCT05266456. Accessed October 7, 2026. https://cdn.clinicaltrials.gov/large-docs/56/NCT05266456/Prot_002.pdf