Home›Drug Pipeline› VAX-31 meets non-inferiority and superiority criteria for opsonophagocytic activity compared to PCV20
VAX-31 meets non-inferiority and superiority criteria for opsonophagocytic activity compared to PCV20Trial shows new pneumococcal vaccine shows strong immune response
The Lancet. Infectious diseasesPublished September 18, 2026Study authors: Wassil James, Fairman Jeff, Fierro Carlos A, Clark James, Bennett Sean, Johnson Derek, Jiang Qin, Mi…PubMed ↗NCT06151288 ↗DOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
Note that VAX-31 met non-inferiority for shared serotypes and superiority for unique serotypes compared to PCV20.
This Phase 1/2 randomized clinical trial enrolled 1015 healthy, pneumococcal-naive adults aged 50 years or older across 25 sites in the USA. The study compared VAX-31 (administered in low, mid, and high doses) against PCV20 to evaluate safety, tolerability, and immunogenicity over a 6-month follow-up period.
Regarding immunogenicity, the mid-dose and high-dose VAX-31 groups met or exceeded the non-inferiority criterion for serotypes shared with PCV20. The low-dose group met the criterion for 18 of 20 serotypes. Furthermore, all 11 serotypes unique to VAX-31 met the superiority criterion across all three dosage levels.
Safety data indicated that VAX-31 was well tolerated with a profile similar to PCV20. Solicited adverse events occurred in 76% (low-dose), 78% (mid-dose), 83% (high-dose), and 71% (PCV20) of participants, with most being mild or moderate. Serious adverse events were low: 2 (1%) in low-dose, 3 (1%) in mid-dose, 5 (2%) in high-dose, and 3 (1%) in PCV20, with none related to the vaccine.
A primary limitation of this study is that no formal hypothesis testing was performed. While the results suggest VAX-31 provides broad-spectrum coverage and high immunogenicity, these findings are preliminary and require Phase 3 confirmation before influencing public health policy.
How this fits prior evidence
How this fits prior evidence: This study addresses a gap in the evaluation of newer pneumococcal vaccine candidates. While the ACIP recommends 20-valent pneumococcal conjugate vaccine for children in the United States, this trial evaluates the immunogenicity of VAX-31 compared to PCV20 in adults. The results extend the understanding of available vaccine options for pneumococcal disease, though the trial's lack of formal hypothesis testing limits immediate policy implications.
Protecting against pneumococcal disease is a major goal for older adults. A recent trial looked at a new vaccine called VAX-31 to see how it compares to the current standard, PCV20. The study involved over 1,000 healthy adults in the United States to see if the new option could provide broad protection.
Researchers found that both the mid-dose and high-dose versions of VAX-31 met the goals for immune activity against shared germs. Additionally, VAX-31 showed superior immune activity against 11 specific types of germs that it covers uniquely. The low-dose version also showed strong results for most of the germs it targets.
Safety is a top priority for any new vaccine. The study found that VAX-31 was well tolerated, with a safety profile similar to the current PCV20 vaccine. While some people reported mild to moderate reactions within the first week, these were common across all groups. Because this was a Phase 1/2 trial, more large-scale testing is needed to confirm these findings.
What this means for you:
VAX-31 shows strong immune protection and a safety profile similar to current pneumococcal vaccines.
Common questions
Is the new VAX-31 vaccine safe for adults?
Yes, the study found that VAX-31 was well tolerated by adults aged 50 and older. Its safety profile was similar to the current PCV20 vaccine. While some people reported mild or moderate reactions within the first week, these were common across all groups, and only a small number of serious events occurred, none of which were related to the vaccine.
How does VAX-31 compare to the current PCV20 vaccine?
The trial showed that mid-dose and high-dose VAX-31 met or exceeded the requirements for immune activity against shared germs. Furthermore, VAX-31 showed superior immune activity against 11 specific types of germs that are unique to it. The safety profile for VAX-31 was found to be similar to the current PCV20 vaccine.
What did the study find about the different doses of VAX-31?
The study tested three doses: low, mid, and high. The mid and high doses met the goals for immune activity against shared germs. The low-dose version met the criteria for 18 out of 20 shared serotypes. All three doses showed superior immune activity against the 11 germ types unique to VAX-31.
BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have substantially reduced vaccine-type pneumococcal disease, yet a considerable burden of adult pneumococcal disease remains due to persistent serotype diversity and replacement. This study aimed to evaluate the safety, tolerability, and immunogenicity of VAX-31, a 31-valent PCV candidate designed to provide broad serotype coverage and higher immunogenicity.
METHODS: This phase 1/2, double-blinded, active-controlled, parallel-group, dose-finding randomised clinical trial enrolled healthy, pneumococcal-naive adults aged 50 years or older from 25 clinical sites in the USA. Participants were block randomised (1:1:1:1) using a web-based randomisation and trial management system to receive a dose of intramuscular low-dose, mid-dose, or high-dose VAX-31, or 20-valent PCV (PCV20). VAX-31 doses were defined by polysaccharide content: 1·1 μg (low), 2·2 μg (mid), or 3·3 μg (high) for all serotypes except 1, 5, and 22F, which were dosed at 1·65 μg (low), 3·3 μg (mid), and 4·4 μg (high). Investigators, participants, and trial personnel were masked to treatment assignment. Participants were followed up for 6 months, with blood samples collected at baseline and 1 month. Primary safety outcomes, assessed in the safety population (all vaccinated participants with safety data), included solicited local and systemic adverse events within 7 days after vaccination, unsolicited adverse events within 1 month, and serious adverse events, medically attended adverse events, and new-onset chronic illnesses up to 6 months. Safety was evaluated overall and across prespecified age groups. Secondary immunogenicity outcomes were assessed in the immunogenicity-evaluable population (no major protocol deviations affecting immunogenicity and with evaluable serum samples) and included serotype-specific opsonophagocytic activity (OPA) geometric mean titres (GMTs) and IgG geometric mean concentrations at 1 month. Although no formal hypothesis testing was performed, the lower bound of the two-sided 95% CIs for OPA GMT ratios (VAX-31 to PCV20) was compared using precedent PCV licensure criteria: non-inferiority of at least 0·5 for serotypes shared with PCV20 and superiority of at least 2·0 for novel serotypes. This study is registered at ClinicalTrials.gov (NCT06151288).
FINDINGS: Between Nov 8, 2023, and Jan 10, 2024, 1015 participants were enrolled and randomly assigned; 255 participants were vaccinated with low-dose VAX-31, 254 participants were given mid-dose VAX-31, 253 participants were given high-dose VAX-31, and 253 participants were given PCV20. In 1015 total participants, the mean age was 59·8 years (SD 6·7), 609 (60%) were female, and 406 (40%) were male. Solicited adverse events were reported in 192 (76% [95% CI 70-81]) of 253 participants given low-dose VAX-31, 197 (78% [72-83]) of 254 participants given mid-dose VAX-31, 210 (83% [78-87]) of 253 participants given high-dose VAX-31, and 180 (71% [65-77]) of 252 participants given PCV20; most events were mild or moderate. Serious adverse events occurred in two (1% [0-5]) of 255 participants given low-dose VAX-31, three (1% [0-3]) of 254 participants given mid-dose VAX-31, five (2% [1-5]) of 253 participants given high-dose VAX-31, and three (1% [0-3]) of 253 participants given PCV20; none were considered related to study vaccine, and no deaths occurred. The VAX-31 mid-dose and high-dose groups met or exceeded the precedent OPA non-inferiority criterion for all 20 serotypes shared with PCV20, while the low-dose group met the criterion for 18 of 20 serotypes. All 11 serotypes unique to VAX-31 met the precedent OPA superiority criterion at all doses.
INTERPRETATION: Across all doses, VAX-31 was well tolerated, had a safety profile similar to PCV20, and elicited robust OPA responses across all 31 serotypes. These data further validate the potential for VAX-31 to provide broad-spectrum coverage with high immunogenicity to protect against circulating and historically prevalent serotypes and, if confirmed in phase 3 studies, to have important public health and vaccination policy implications.
FUNDING: Vaxcyte.
