Dataset Information

Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial.

ABSTRACT:

Background

Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone or as a bivalent preparation with the prototype vaccine (NVX-CoV2373) to assess antibody responses to SARS-CoV-2.

Methods

Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or the bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed.

Results

Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated a superior neutralizing antibody response to BA.1 vs NVX-CoV2373 (n = 274) at day 14 (geometric mean titer ratio, 1.6; 95% CI, 1.33-2.03). Seroresponse rates were 73.4% (91/124; 95% CI, 64.7-80.9) for NVX-CoV2515 vs 50.9% (59/116; 95% CI, 41.4-60.3) for NVX-CoV2373. All formulations were similarly well tolerated.

Conclusions

NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant as compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.

Clinical trials registration

ClinicalTrials.gov (NCT05372588).

SUBMITTER: Bennett C

PROVIDER: S-EPMC11272042 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial.

Bennett Chijioke C Rivers E Joy EJ Woo Wayne W Bloch Mark M Cheung King K Griffin Paul P Mohan Rahul R Deshmukh Sachin S Arya Mark M Cumming Oscar O Neville A Munro AM Pardey Toni McCallum TM Plested Joyce S JS Cloney-Clark Shane S Zhu Mingzhu M Kalkeri Raj R Patel Nita N Buchanan Agi A Marcheschi Alex A Swan Jennifer J Smith Gale G Cho Iksung I Glenn Gregory M GM Walker Robert R Mallory Raburn M RM

The Journal of infectious diseases 20240701 1

<h4>Background</h4>Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone or as a bivalent preparation with the prototype vaccine (NVX-CoV2373) to assess antibody responses to SARS-CoV-2.<h4>Methods</h4>Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or th ...[more]

PMID: 39052718

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Project description:BackgroundThe emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019.MethodsIn an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were randomly assigned to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 μg (15 μg of BNT162b2 + 15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2 + 30 μg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 μg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants.ResultsA total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 μg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 μg) were also noninferior to BNT162b2 (30 μg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-μg bivalent BA.1 than with 30-μg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 μg). Adverse events were more common in the 30-μg monovalent-BA.1 (8.5%) and 60-μg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%).ConclusionsThe candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 μg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.).

Project description:In addition to the original monovalent vaccines available for SARS-CoV-2, bivalent vaccines covering wild-type (WT) and Omicron BA.1 are also available. However, there is a lack of real-world data on the immunogenicity of bivalent vaccines as second boosters against the dominant Omicron sublineages, including BA.2 and BA.5. Healthcare workers (n = 565) who received the first booster vaccination were followed for 2 weeks after the second booster dose of the monovalent mRNA-1273 (WT group, n = 168) and bivalent BNT162b2 (WT+BA.1 group, n = 23) vaccines. Participants with previous SARS-CoV-2 infections were excluded from the study. The anti-receptor binding domain (RBD) antibody levels after the second booster dose in the WT and WT+BA.1 group were similar (median [interquartile range], 26,262.0 [16,951.0 to 38,137.0] U/mL versus 24,840.0 [14,828.0 to 41,460.0] U/mL, respectively). Although the neutralization activities of the pooled sera were lower against BA.5 than against other variants in both groups, the activities against BA.2 and BA.5 in the WT+BA.1 group were higher than those of the WT group in both pseudotyped and live virus assays. Vaccine-related symptoms, including systemic and local symptoms, were strongly correlated with anti-RBD antibody levels and neutralizing titers. In conclusion, the second booster dose of the bivalent (WT/Omicron BA.1) vaccine induced higher neutralizing activity against BA.2 and BA.5 than that of the original monovalent vaccine. IMPORTANCE Although Omicron BA.1-containing bivalent vaccines have been authorized, real-world data validating their safety and antibody responses remain scarce. We conducted a prospective longitudinal study to assess the safety, immunogenicity, and reactogenicity of the second booster dose with the Omicron BA.1 bivalent vaccine in health care workers. Compared with the original monovalent vaccine, the bivalent (WT+BA.1) vaccine elicited higher levels of neutralizing antibodies against the Omicron BA.2 and BA.5 subvariants. The frequency of adverse events after the second booster dose was similar to that of the monovalent vaccine. BA.5-neutralizing antibodies induced by the bivalent Omicron BA.1-containing vaccine were expected to decline. A prospective longitudinal study should be performed to determine the persistence of the humoral immunity.

Dataset Information

Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial.

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial.

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