Publication date: Sep 09, 2025
Covid-19 vaccines are updated to match circulating strains based on reasoning that better strain-matched immunogenicity should provide better protection. Randomized evidence with disease endpoints to support strain matching is lacking. We evaluated COVID-19 incidence among adults randomized to a second booster of Prototype or Omicron-based vaccines. COVAIL was a four-stage Phase 2 clinical trial; results from Stages 1 (mRNA-1273 [Moderna]) and 2 (BNT162b2 [Pfizer/BioNTech]) are described here. Adults who had received a primary series and one booster of an authorized COVID-19 vaccine were eligible. Participants received one dose of either Prototype vaccine or a monovalent or bivalent Omicron BA. 1 vaccine. SARS-CoV-2 neutralization titers (ID) were measured pre- and post-vaccination. Covariate-adjusted cumulative COVID-19 incidence and Cox regression analyses were conducted separately for each stage. 706 participants with pre- and day 15 post-vaccination ID titers (n = 503 in Stage 1, n = 203 in Stage 2) were included. Within stages, participant characteristics and baseline ID titers were similar between Prototype and Omicron-based arms. There was no difference in cumulative COVID-19 incidence for Prototype vs. Omicron-based vaccine in Stage 1 (RR 1. 04, 95 % CI 0. 73-1. 48), while incidence was higher among Prototype recipients in Stage 2 (RR 2. 56, 1. 44-4. 52). Cox regression analysis showed no difference in Stage 1 (HR 1. 04, 0. 68-1. 58), but higher incidence for Prototype recipients in Stage 2 (HR 2. 95, 1. 52-5. 72). Omicron-based vaccines as second boosters were more protective against COVID-19 relative to Prototype among those receiving BNT162b2 but not mRNA-1273. Differences between stages such as force of infection, antigen matching, and vaccine differences may explain this finding. govRegistry Number: NCT05289037.
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| Concepts | Keywords |
|---|---|
| Nct05289037 | COVID-19 |
| Randomized | mRNA vaccine |
| Stage | SARS-CoV-2 |
| Vaccine | Vaccine efficacy |
| Variant |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| drug | DRUGBANK | Tropicamide |
| disease | MESH | infection |