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

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant sparked concern due to its fast spread and the unprecedented number of mutations in the spike protein that enables it to partially evade spike-based COVID-19 vaccine-induced humoral immunity. In anticipation of a potential need for an Omicron spike-based vaccine, we generated an Ad26 vector encoding an Omicron (BA.1) spike protein (Ad26.COV2.S.529). Ad26.COV2.S.529 encodes for a prefusion stabilized spike protein, similar to the current COVID-19 vaccine Ad26.COV2.S encoding the Wuhan-Hu-1 spike protein. We verified that spike expression by Ad26.COV2.S.529 was comparable to Ad26.COV2.S. Immunogenicity of Ad26.COV2.S.529 was then evaluated in naïve mice and SARS-CoV-2 Wuhan-Hu-1 spike pre-immunized hamsters. In naïve mice, Ad26.COV2.S.529 elicited robust neutralizing antibodies against SARS-CoV-2 Omicron (BA.1) but not to SARS-CoV-2 Delta (B.1.617.2), while the opposite was observed for Ad26.COV2.S. In pre-immune hamsters, Ad26.COV2.S.529 vaccination resulted in robust increases in neutralizing antibody titers against both SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2), while Ad26.COV2.S vaccination only increased neutralizing antibody titers against the Delta variant. Our data imply that Ad26.COV2.S.529 can both expand and boost a Wuhan-Hu-1 spike-primed humoral immune response to protect against distant SARS-CoV-2 variants.

COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection

“…Some small-scale animal studies found Omicron-specific mRNA-based boosters offer little advantage over the original vaccines in rhesus macaques and mice that were previously immunized with 2 doses of the original vaccine [ 239 , 240 ]. Nonetheless, boosting with Omicron-specific mRNA (mRNA-1273.529) and Ad26 viral vector (Ad26.COV2.S.529) vaccine candidates both induced stronger Omicron-neutralizing responses in pre-immunized rodents when compared to boosting with the original vaccine [ 240 , 241 ]. Additionally, the timing of boosting should be optimized, as preexisting immunity may compromise the effect of the booster dose [ 130 , 242 ].…”

“…Additionally, the timing of boosting should be optimized, as preexisting immunity may compromise the effect of the booster dose [ 130 , 242 ]. Notably, animal studies also found Omicron-specific vaccines induced potent antibodies and immunity against Omicron but not the ancestral strain in vaccine-naive mice and Syrian hamsters [ 241 – 243 ]. A serological study of vaccine-naive individuals infected with Omicron also showed that their sera contain nAbs against Omicron but not the other variants [ 244 ].…”