Omicron-specific mRNA vaccine elicits potent immune responses in mice, hamsters, and nonhuman primates

Abstract

SARS-CoV-2 has infected more than 400 million people around the globe and caused millions of deaths. Since its identification in November 2021, Omicron, a highly transmissible variant, has become the dominant variant in most countries. Omicron highly mutated spike protein, the main target of vaccine development, significantly compromises the immune protection from current vaccination. We develop an mRNA vaccine (SOmicron-6P) based on an Omicron-specific sequence. In mice, SOmicron-6P shows superior neutralizing antibodies inducing abilities to a clinically approved inactivated virus vaccine, a clinically approved protein subunit vaccine, and an mRNA vaccine (SWT-2P) with the same sequence of BNT162b2 RNA. Significantly, SOmicron-6P induces a 14.4~27.7-fold and a 28.3~50.3-fold increase of neutralizing activity against the pseudovirus of Omicron and authentic Omicron compared to SWT-2P, respectively. In addition, two doses SOmicron-6P significantly protects Syrian hamsters against challenge with SARS-CoV-2 Omicron variant and elicits high titers of nAbs in a dose-dependent manner in macaques. Our results suggest that SOmicron-6P offers advantages over current vaccines, and it will be helpful for those with weak immunity.

Immunogenicity of an Ad26-based SARS-CoV-2 Omicron Vaccine in Naïve Mice and SARS-CoV-2 Spike Pre-immune Hamsters

“…Ad26.COV2.S.529 vaccination resulted in similar Delta spike neutralization titers as Ad26.COV2.S in pre-immune hamsters, but Delta neutralizing titers were undetectable or very low in Ad26.COV2.S.529 vaccinated naïve mice. The latter is consistent with data from naïve animals vaccinated with Omicron-specific mRNA vaccines [30][31][32][33] and also in Omicron-infected hamsters 37 where Delta spike neutralizing antibodies were undetectable. This suggests that an immunization with a heterologous spike protein as encoded by Ad26.COV2.S.529 induces a more broadly neutralizing antibody response in animals with pre-existing immunity to ancestral Wuhan-Hu-1 spike than a homologous spike protein immunization.…”

“…These immune functions seem largely conserved against Omicron [17][18][19][20] and may have contributed to the effectiveness of a homologous booster with Ad26.COV2.S against hospitalization during the Omicron wave and to the effectiveness in macaques against a high-dose challenge with SARS-CoV-2 Omicron 16,29 . Ad26.COV2.S.529, but not Ad26.COV2.S, induced robust Omicron (BA.1) spike neutralizing titers in naïve mice, in line with studies with Omicron-based RNA vaccines in naïve animals [30][31][32][33][34] . These differences in Omicron neutralizing titers are not attributed to differences in spike expression as we have shown that the expression of spike in vitro is comparable after transduction with Ad26.COV2.S and Ad26.COV2.S.529.…”