Boosting with variant-matched adenovirus-based vaccines promotes neutralizing antibody responses against SARS-CoV-2 Omicron sublineages in mice

Abstract

Global spreading of SARS-CoV-2 Omicron subvariants, such as BA.4, BA.5, and XBB.1.5, has been leading the recent wave of COVID-19. Unique mutations in the spike proteins in these emerging Omicron subvariants caused immune evasion from the pre-existing protective immunity induced by vaccination or natural infection. We previously developed AdCLD-CoV19-1, a non-replicating recombinant adenoviral vector that encode receptor binding domain of spike protein of ancestral SARS-CoV-2 strain. Based on the same recombinant adenoviral vector platform, we constructed updated vaccines that cover unique mutations found in each Omicron subvariants including BA.1, BA.2, BA.4.1, and BA.5. Preclinical studies reveal that each updated vaccine as a booster shot following primary vaccination targeting ancestral strain most effectively improved neutralizing antibody responses against pseudo-virus of its respective strain. Of note, boosting with a vaccine targeting the BA.1 or BA.2 Omicron subvariant was most effective in neutralization against the pseudo-virus of BA.2.75 strain, whereas BA.4.1/5-adapted booster shots were most effective in neutralization against BQ.1, BQ1.1, and BF.7. Therefore, it is imperative to develop a vaccination strategy that can cover the unique spike mutations of currently circulating Omicron subvariants to prevent the next wave of COVID-19.