Omicron-Specific and Bivalent Omicron-Containing Vaccine Candidates Elicit Potent Virus Neutralisation in the Animal Model

Background Omicron variant (B. 1.1.529) is able to escape from naturally acquired and vaccine-induced immunity, which mandates updating the current COVID-19 vaccines. Here, we investigated and compared the neutralising antibody induction of the ancestral variant-based BIV1-CovIran vaccine, the Omicron variant-based BIV1-CovIran Plus vaccine, and the novel bivalent vaccine candidate, BBIV1-CovIran, against the Omicron and ancestral Wuhan variants on the rat model. Methods Viruses were isolated from a clinical specimen and virus characterisation performed. After inactivating the viral particles, the viruses were purified and formulated. Bivalent vaccines were a composition of 2.5 μg (5 μg total) or 5 μg (10 μg total) doses of each ansectral-based and Omicron-based monovalent vaccine. Subsequently, the potency of the monovalent and bivalent vaccines was investigated using the virus neutralisation test (VNT). Results The group that received three doses of the Omicron-specific vaccine demonstrated neutralisation activity against the Omicron variant with a geometric mean titer of 337.8. However, three doses of the Wuhan variant-specific vaccine could neutralise the Omicron variant at a maximum of 1/32 serum dilution. The neutralisation activity of the Omicron-specific vaccine, when administered as the booster dose after two doses of the Wuhan variant-specific vaccine, was 100% against the Omicron variant and the Wuhan variant at 1/64 and 1/128 serum dilution, respectively. Three doses of 5 μg bivalent vaccine could effectively neutralise both variants at the minimum of 1/128 serum dilution. The 10 μg bivalent vaccine at three doses showed even higher neutralisation titers: geometric mean titer of 338.0 against Omicron and 445.7 against Wuhan). Conclusion It is shown that the candidate bivalent vaccine could elicit a potent immune response against both Wuhan-Hu-1 and Omicron BA.1 variants. Therefore, we plan to evaluate the updated vaccine in the clinical trial setting.