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Clinical Trial
. 2025 May 10:55:127046.
doi: 10.1016/j.vaccine.2025.127046. Epub 2025 Apr 2.

Immunogenicity and safety of a monovalent Omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine in previously unvaccinated, SARS-CoV-2 seropositive participants: Primary day-28 analysis of a phase 2/3 open-label study

Katia Alves  1 , Alex Kouassi  1 , Joyce S Plested  1 , Raj Kalkeri  1 , Katherine Smith  1 , Muneer Kaba  1 , Joy Nelson  1 , Mingzhu Zhu  1 , Shane Cloney-Clark  1 , Zhaohui Cai  1 , Raburn M Mallory  1 , Fernando Noriega  2 ; 2019nCoV-313 Study Investigators  1
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Free article
Clinical Trial

Immunogenicity and safety of a monovalent Omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine in previously unvaccinated, SARS-CoV-2 seropositive participants: Primary day-28 analysis of a phase 2/3 open-label study

Katia Alves et al. Vaccine. .
Free article

Abstract

Background: Most of the population has been infected with SARS-CoV-2 and, thus, is primed by natural exposure. As such, it was assessed whether a single dose of the monovalent XBB.1.5 vaccine, NVX-CoV2601, elicited a comparable immune response to XBB.1.5 in seropositive unvaccinated participants to that in previously vaccinated participants, thereby allowing the former to forego a two-dose primary series.

Methods: In this phase 2/3, open-label, single-arm study (2019nCoV-313/NCT05975060 [group 2]), vaccine-naive participants ≥18 years with previous SARS-CoV-2 infection received one dose of NVX-CoV2601. This analysis compared the 28-day immunogenicity and safety of NVX-CoV2601 in vaccine-naive and previously vaccinated (≥3 prior mRNA-based vaccines, from 2019nCoV-313 group 1) participants. Noninferiority of neutralizing antibody (nAb) response in vaccine-naive versus vaccinated participants was the primary objective. The day-28 geometric mean titer (GMT) ratio (GMTR) and seroresponse rate (SRR; percentage of participants with a ≥4-fold rise in antibody response from baseline) were measured, and safety was assessed.

Results: Of the participants enrolled from September 11 to November 15, 2023, per-protocol sets included 306/338 (90.5%) vaccine-naive and 309/332 (93.1%) vaccinated participants. At day 28, adjusted GMTs (95% CI) against XBB.1.5 in the vaccine-naive and vaccinated groups were 1491.5 (1277.5-1741.4) and 841.4 (723.9-978.0), respectively. The vaccine-naive-vaccinated nAb GMTR was 1.8 (95% CI 1.43-2.20) and SRRs were 74.3% and 64.3% for vaccine-naive and vaccinated participants, respectively (SRR difference: 10.0 [95% CI 2.6-17.4]). No new safety signals or events of special interest were reported.

Conclusions: A single dose of NVX-CoV2601 in vaccine-naive participants with a history of SARS-CoV-2 infection elicited a robust neutralizing antibody response that was noninferior to that observed in vaccinated participants. The vaccine was well-tolerated. These data support the use of NVX-CoV2601 as a single dose, regardless of prior vaccination history.

Trial registration: NCT05975060.

Keywords: COVID-19; Single-dose; Vaccination; Variant.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katia Alves reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Alex Kouassi reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Joyce S. Plested reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Raj Kalkeri reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Katherine Smith reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Muneer Kaba reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Joy Nelson reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Mingzhu Zhu reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Shane Cloney-Clark reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Zhaohui Cai reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Raburn M. Mallory reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. Fernando Noriega reports a relationship with Novavax, Inc. that includes: employment and equity or stocks. This study was funded by Novavax, Inc. The authors received medical writing and editorial support funded by the study sponsor. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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