Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35...

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants pose a threat to existing COVID-19 vaccine efficacy.
• The emergence of diverse Omicron sub-lineages necessitates updated vaccine strategies to combat breakthrough and re-infections.

Purpose of the Study:

• To develop and evaluate multivalent vaccines against SARS-CoV-2 Omicron subvariants.
• To assess the immunogenicity and cross-neutralization capabilities of novel bivalent and trivalent adenoviral vector-based vaccines.

Main Methods:

• Development of bivalent (BA.5/BA.2.75) and trivalent (XBB/BN.1/BQ.1.1, XBB.1.5/BN.1/BQ.1.1) non-replicating recombinant adenoviral vector vaccines.
• Comparison of immune responses and cross-neutralization activity induced by monovalent versus multivalent vaccines in mouse and macaque models.

Main Results:

• Multivalent vaccines demonstrated improved cross-neutralization compared to monovalent counterparts.
• The BA.5/BA.2.75 bivalent and XBB/BN.1/BQ.1.1, XBB.1.5/BN.1/BQ.1.1 trivalent vaccines showed enhanced immune responses.
• Developed vaccines effectively elicited neutralizing antibodies against a broad range of SARS-CoV-2 variants.

Conclusions:

• Multivalent adenoviral vector vaccines are effective in enhancing immunity against circulating Omicron subvariants.
• These updated vaccines provide broad neutralization against diverse SARS-CoV-2 variants, offering a promising strategy for future COVID-19 control.