Development of a two-component recombinant vaccine for COVID-19

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• COVID-19 remains a significant global health threat despite the WHO declaring an end to the public health emergency.
• Vaccination is a key strategy for COVID-19 prevention.
• The Spike (S) protein's receptor binding domain (RBD) and N-terminal domain (NTD) are critical for inducing neutralizing antibodies.

Purpose of the Study:

• To develop and evaluate a novel two-component recombinant vaccine for COVID-19.
• To determine the optimal ratio of RBD-Fc and NTD-Fc proteins for vaccine formulation.
• To assess the immunogenicity and efficacy of this vaccine as a booster strategy.

Main Methods:

• Developed a two-component vaccine using RBD-Fc and NTD-Fc proteins.
• Immunized mice with varying ratios of RBD-Fc/NTD-Fc, including sequential vaccination with inactivated SARS-CoV-2 vaccines.
• Measured IgG and neutralizing antibodies (against prototype and omicron strains), and assessed T-cell responses (IL-4, IFN-γ, IL-2, IL-10).

Main Results:

• An optimal RBD-Fc/NTD-Fc ratio of 3:1 was identified.
• The two-component vaccine induced potent and durable IgG and neutralizing antibodies in both homologous and sequential vaccination regimens.
• Heterologous boosting with the two-component vaccine resulted in higher neutralizing antibody titers compared to homologous boosting and elicited balanced Th1/Th2 immune responses.

Conclusions:

• A novel two-component recombinant vaccine based on RBD-Fc and NTD-Fc proteins (3:1 ratio) demonstrates high immunogenicity.
• This vaccine formulation is a potential candidate for a COVID-19 booster strategy.
• Further research may explore its application in diverse populations and against emerging SARS-CoV-2 variants.