Rational prediction of immunogenicity clustering through cross-reactivity analysis of thirteen SARS-CoV-2 variants

Area of Science:

• Virology and Immunology
• Vaccine Development
• Infectious Disease Research

Background:

• SARS-CoV-2 variants, like Omicron, pose a threat to vaccine-induced immunity.
• Continuous mutation necessitates broad-spectrum immunogens to counter evolving variants.
• Understanding immunogenicity relationships among SARS-CoV-2 variants is crucial for effective vaccine design.

Purpose of the Study:

• To evaluate the immunogenicity relationships among SARS-CoV-2 variants from D614G to XBB.
• To assess the efficacy of different immunization strategies against SARS-CoV-2 variants.
• To identify optimal antigen selection for broad-spectrum vaccine protection.

Main Methods:

• Guinea pig vaccination with diverse SARS-CoV-2 variants (D614G to XBB).
• Three immunization strategies were tested: three-dose monovalent, three-dose bivalent, and a two-dose D614G followed by a variant booster.
• Analysis of immunogenicity clusters and neutralizing antibody levels.

Main Results:

• Three distinct immunogenicity clusters were identified: Cluster 1 (D614G, Alpha, Beta, Gamma, Delta), Cluster 2 (BA.1, BA.2, BA.2.75), and Cluster 3 (BA.2.75.2, BA.5, BF.7, BQ.1.1, XBB).
• Broad-spectrum protection was achieved with bivalent immunogens or D614G/XBB combination strategies.
• XBB boosting resulted in higher neutralizing antibody levels compared to D614G and XBB equivalent dosing.

Conclusions:

• Combined immunization strategies, particularly using bivalent immunogens or D614G with XBB, can provide broad-spectrum protection against SARS-CoV-2 variants.
• Vaccine antigen selection should prioritize antigenic alterations across variants to minimize the need for frequent updates.
• The findings support the development of variant-proof vaccines by focusing on key antigenic changes.