Development and characterization of a bivalent mRNA vaccine targeting the Delta and Omicron variants of SARS-CoV-2

📖 Top 20% JournalSep 30, 2025Human vaccines & immunotherapeutics

Development and testing of an mRNA vaccine targeting both Delta and Omicron COVID-19 variants

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mRNA Technology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

ARCoV-Biv induced mean neutralization titers (NT50) of 87,556.33 against Delta and 52,634.67 against Omicron BA.1.

The bivalent targets the receptor-binding domains of the Delta and Omicron BA.1 variants.
In vitro characterization indicated that ARCoV-Biv has favorable physicochemical properties similar to existing monovalent mRNA vaccines.
Immunization with ARCoV-Biv under a two-dose regimen resulted in significant increases in responses compared to pre-booster levels.
ARCoV-Biv enhanced neutralizing activity against multiple variants, including BA.2.12.1 and BA.4/5, following prior immunization with a prototype vaccine.
Compared to mRNA-1273.214, ARCoV-Biv showed a higher breadth of neutralization against Delta and Omicron BA.1, as well as improved T-cell responses.

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The emergence of the Omicron variant of SARS-CoV-2 has led to a decrease in vaccine efficacy and contributed to the ongoing epidemic of COVID-19. Consequently, there is an urgent need to develop new vaccines targeting the emerging SARS-CoV-2 variants. To address this, we developed a bivalent , ARCoV-Biv, targeting the receptor-binding domains (RBDs) of Delta and Omicron BA.1 variants, which were selected for their strong transmissibility and immune escape potential, necessitating an updated vaccine formulation for broader protection. In vitro characterization showed that ARCoV-Biv exhibited favorable physicochemical properties comparable to the monovalent mRNA vaccines. Then, the immunogenicity of the vaccine candidates under a two-dose prime immunization regimen were further analyzed, demonstrating that ARCoV-Biv induced a broad response, with mean neutralization titers (NT50) of 87,556.33 against Delta (B.1.617.2) and 52,634.67 against Omicron BA.1, representing 71.19-fold and 399.72-fold increases, respectively, compared to the levels prior to booster immunization. It also elicited robust cellular immunity against different variants. Furthermore, the booster effect of ARCoV-Biv following the administration of two doses of ARCoV (prototype vaccine) was evaluated. The results showed that ARCoV-Biv significantly enhanced the neutralizing activity of immunized serum against BA.2.12.1 (5,700.67) and BA.4/5 (1,289.5) in addition to the prototype, Delta, and BA.1 variants. These findings suggest that ARCoV-Biv may serve as a foundational platform for future vaccine optimization against newly emerging SARS-CoV-2 strains. Compared to mRNA-1273.214 (Moderna), a bivalent vaccine, ARCoV-Biv demonstrated a higher neutralization breadth against Delta and Omicron BA.1, along with enhanced T-cell responses, indicating potential advantages in cross-variant protection and durability.