The Cross-Protective Immunity Landscape Among Different SARS-CoV-2 Variant RBDs

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The ongoing emergence of SARS-CoV-2 variants poses a significant threat to global public health, necessitating the development of vaccines with broader protective capabilities.
• Existing vaccines, while effective, show reduced efficacy against newer variants due to immune escape mechanisms.

Purpose of the Study:

• To evaluate the cross-protective immunity induced by different SARS-CoV-2 receptor-binding domain (RBD) antigens against emerging variants.
• To identify optimal antigens for vaccine strain selection and the design of universal COVID-19 vaccines.

Main Methods:

• Expression and purification of wild-type (WT), Alpha, Beta, Delta, and Lambda RBD proteins.
• Immunization of mice with monovalent and pentavalent RBD antigens.
• Assessment of IgG antibody titers and pseudovirus neutralization assays against various SARS-CoV-2 variants (WT, Alpha, Beta, Delta, Lambda, Omicron).

Main Results:

• All tested RBD antigens induced high IgG titers against homologous and heterologous variants.
• Antibodies from WT RBD immunization showed reduced neutralization against Beta, Delta, Lambda, and Omicron variants.
• Beta RBD and multivalent RBD antigens elicited broader cross-neutralizing antibody responses compared to other monovalent antigens.

Conclusions:

• Beta RBD and multivalent antigens are promising candidates for developing next-generation COVID-19 vaccines offering broader protection.
• These findings provide crucial data for selecting vaccine strains to combat the evolution of SARS-CoV-2 variants.