Strategy to develop broadly effective multivalent COVID-19 vaccines based on Ad5/35 platform

What is it about?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants.

Featured Image

Photo by Martin Sanchez on Unsplash

Photo by Martin Sanchez on Unsplash

Why is it important?

The emergence of highly diverse sub-lineages within the SARS-CoV-2 Omicron variant poses a significant threat to the efficacy of existing COVID-19 vaccines, leading to breakthrough infections and re-infections. Therefore, developing new multivalent vaccines that can provide broad neutralization of circulating and emerging Omicron variants is crucial. Herein, we developed bivalent and trivalent Omicron variant-specific vaccines using phylogenetic trees and antigenic cartography and demonstrated their superior ability to neutralize a wide range of variants. The AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 or XBB.1.5/BN.1/BQ.1.1 trivalent vaccine could elicit broader neutralizing antibodies against newly emerged and prevailing circulating Omicron variants, including XBB.1.5, XBB.1.16, EG.5.1, FL.1.5.1, and BA.2.86. Determining future booster combinations before new variants become widespread will be a crucial challenge in combating COVID-19.