Development of broadly protective COVID-19 vaccine against up-to-date variants based on adenovirus type 5/35 vector platform.

Abstract

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron strain has evolved into a highly divergent variant with several sub-lineages. These new emerging variants could impair the protective efficacy of COVID-19 vaccines based on the ancestral spike, causing breakthrough infections and re-infections. Therefore, it is imperative to develop new multivalent vaccines that can provide broad protection against currently prevalent new variants. We previously developed AdCLD-CoV19-1 OMI, an Ad5/35 platform based non-replicating recombinant adenoviral vector that encodes the spike protein of BA.1, and currently performing clinical studies. We also constructed vaccines against emerging subvariants such as BA.5, BA.2.75, XBB, BQ.1.1, and BN.1 using the Ad5/35 platform and evaluated their immunogenicity by sera from vaccinated mice. To develop the bivalent vaccine, we selected a combination of BA.5 and BA.2.75 vaccines by antigenic cartography map based on cross-neutralizing activities. We found that a bivalent vaccine could induce broadly neutralizing antibodies against the predominant circulating strains and improved cross-neutralization capacity. These data suggest that the bivalent vaccine broadens immunity against current prevalent omicron subvariants. We further investigate combinations of next-generation multivalent vaccines to confer broad protection against new subvariants. Based on the results of preclinical studies, clinical trials of the polyvalent vaccines will be conducted. Supported by grant from the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (2020M3A9I2107463)