Higher Day 29 neutralizing antibody levels after mRNA-1283 or mRNA-1273 vaccination were linked to lower COVID-19 risk, especially against BA.4/BA.5 and XBB.1.5.
Evidence
This immune-correlates analysis of the Phase 3 NextCOVE trial in more than 10,000 participants aged 12 years or older evaluated Day 29 to D614G, BA.4/BA.5, and XBB.1.5 as correlates of risk and protection after vaccination.
Caveat
This was a correlates analysis rather than direct proof of efficacy from antibody levels alone, and the D614G association was borderline and not conventionally significant.
Simplified
SARS-CoV-2 (nAbs) are strongly inversely associated with COVID-19 risk and have correlated with vaccine efficacy across multiple clinical trials conducted during the COVID-19 pandemic. As SARS-CoV-2 continues to evolve in the endemic era, it is important to determine whether nAb levels remain a valid statistical correlate of protection and potential surrogate endpoints for emerging variants. The next-generation COVID-19 vaccine, mRNA-1283, has recently received regulatory approval worldwide. In the Phase 3 NextCOVE trial (NCT05815498), which enrolled more than 10,000 participants aged ≥12 y, mRNA-1283 (10 µg; bivalent ancestral plus Omicron BA.4/BA.5) met the non-inferiority criterion for (rVE) versus mRNA-1273 (50 µg; bivalent) and elicited higher nAb responses. In this correlate analysis of the NextCOVE trial, we evaluated Day 29 nAbs against ancestral D614G, BA.4/BA.5, and XBB.1.5 variants as correlates of risk (CoRs) and correlates of protection (CoPs) for COVID-19 after vaccination with mRNA-1283 or mRNA-1273. Across multiple statistical frameworks, higher Day 29 nAb levels were consistently associated with lower COVID-19 risk and higher estimated rVE. The estimated hazard ratios per 10-fold increase in Day 29 nAbs against D614G, BA.4/BA.5, and XBB.1.5 were 0.70 (95% confidence interval [CI]: 0.48-1.02; = .064), 0.49 (95% CI: 0.41-0.58; < .001), and 0.41 (95% CI: 0.35-0.49; < .001), respectively. These findings indicate that nAb levels, particularly against variants antigenically similar to circulating strains, remain associated with stronger contemporaneous protection against COVID-19. p p p
Key numbers
0.49
Hazard Ratio for COVID-19 Risk Reduction
Per 10-fold increase in Day 29 nAb levels.
6.8
Geometric Mean Fold-Rise for
Against XBB.1.5 variant by Day 29.
50%
Reduction in nAb Levels for COVID-19 Cases
Observed for XBB.1.5 variant.
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