tetano
Editor, Senior Moderator
Vaccine
. 2025 Sep 9:64:127718.
doi: 10.1016/j.vaccine.2025.127718. Online ahead of print. Effect of Omicron BA.1-based compared to prototype booster mRNA vaccination on incidence of COVID-19 in the COVAIL trial
David J Diemert[SUP] 1 [/SUP], Daniel S Graciaa[SUP] 2 [/SUP], Bo Zhang[SUP] 3 [/SUP], Nadine G Rouphael[SUP] 2 [/SUP], Angela R Branche[SUP] 4 [/SUP], Thomas C S Martin[SUP] 5 [/SUP], Lisa A Jackson[SUP] 6 [/SUP], Rachel M Presti[SUP] 7 [/SUP], Satoshi Kamidani[SUP] 8 [/SUP], Siham M Mahgoub[SUP] 9 [/SUP], Tara M Babu[SUP] 10 [/SUP], Craig A Magaret[SUP] 3 [/SUP], Viviana Simon[SUP] 11 [/SUP], Harm van Bakel[SUP] 12 [/SUP], Paul C Roberts[SUP] 13 [/SUP], John H Beigel[SUP] 14 [/SUP], Peter B Gilbert[SUP] 15 [/SUP], Dean Follmann[SUP] 16 [/SUP]; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team
Affiliations
Background: 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.
Methods: 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[SUB]50[/SUB]) were measured pre- and post-vaccination. Covariate-adjusted cumulative COVID-19 incidence and Cox regression analyses were conducted separately for each stage.
Results: 706 participants with pre- and day 15 post-vaccination ID[SUB]50[/SUB] titers (n = 503 in Stage 1, n = 203 in Stage 2) were included. Within stages, participant characteristics and baseline ID[SUB]50[/SUB] 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).
Conclusions: 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.
Clinicaltrials: govRegistry Number: NCT05289037.
Keywords: COVID-19; SARS-CoV-2; Vaccine efficacy; Variant; mRNA vaccine.
. 2025 Sep 9:64:127718.
doi: 10.1016/j.vaccine.2025.127718. Online ahead of print. Effect of Omicron BA.1-based compared to prototype booster mRNA vaccination on incidence of COVID-19 in the COVAIL trial
David J Diemert[SUP] 1 [/SUP], Daniel S Graciaa[SUP] 2 [/SUP], Bo Zhang[SUP] 3 [/SUP], Nadine G Rouphael[SUP] 2 [/SUP], Angela R Branche[SUP] 4 [/SUP], Thomas C S Martin[SUP] 5 [/SUP], Lisa A Jackson[SUP] 6 [/SUP], Rachel M Presti[SUP] 7 [/SUP], Satoshi Kamidani[SUP] 8 [/SUP], Siham M Mahgoub[SUP] 9 [/SUP], Tara M Babu[SUP] 10 [/SUP], Craig A Magaret[SUP] 3 [/SUP], Viviana Simon[SUP] 11 [/SUP], Harm van Bakel[SUP] 12 [/SUP], Paul C Roberts[SUP] 13 [/SUP], John H Beigel[SUP] 14 [/SUP], Peter B Gilbert[SUP] 15 [/SUP], Dean Follmann[SUP] 16 [/SUP]; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team
Affiliations
- PMID: 40930044
- DOI: 10.1016/j.vaccine.2025.127718
Background: 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.
Methods: 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[SUB]50[/SUB]) were measured pre- and post-vaccination. Covariate-adjusted cumulative COVID-19 incidence and Cox regression analyses were conducted separately for each stage.
Results: 706 participants with pre- and day 15 post-vaccination ID[SUB]50[/SUB] titers (n = 503 in Stage 1, n = 203 in Stage 2) were included. Within stages, participant characteristics and baseline ID[SUB]50[/SUB] 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).
Conclusions: 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.
Clinicaltrials: govRegistry Number: NCT05289037.
Keywords: COVID-19; SARS-CoV-2; Vaccine efficacy; Variant; mRNA vaccine.