ChAdOx1 nCoV-19, BNT162b2 and CoronaVac Vaccines Do Not Induce as Strong Neutralising Antibodies with Broad Variant Protection as Infection and Suggest Vaccines that Induce Broader Sterilising Immunity are Essential to Stop the Pandemic

Background: The emergence of SARS-CoV-2 variants raises concerns of reduced COVID-19 vaccine efficacy, increased re-infection rates and disease severity.Methods: We investigated the humoral immunity in naïve and previously infected vaccinees, who have received complete regimes of ChAdOx1 nCoV-19, BNT162b2 or CoronaVac vaccines by means of a SARS-CoV-2 surrogate virus neutralisation test. This measures inhibition of the interaction between the angiotensin-converting enzyme-2 (ACE-2) receptor and the receptor binding domain (RBD) of S protein by vaccinee sera. A cut off at 30% was chosen based on manufacturer protocol.Findings: The ChAdOx1 nCoV-19 and BNT162b2 vaccines induced higher neutralisation with longer durability against the wild type (WT) RBD compared to the CoronaVac vaccine in naïve vaccinees (P<0·0001). Notably, prior infection significantly improved protection in the CoronaVac vaccinees (WT: P= 0·0237). Subsequent investigation on the breadth of SARS-CoV-2 vaccine-induced antibody neutralising responses in naïve vaccinees, revealed that all vaccine platforms cross-protected against Alpha, Beta, Delta, Gamma, and Epsilon variants but the CoronaVac vaccine again induced a much weaker response. All three vaccines failed to protect against Omicron. Importantly, prior infection not only increased the vaccine efficacy against all SARS-CoV-2 variants, but also cross-protected against Omicron, in the ChAdOx1 nCoV-19 and BNT162b2 groups. Prior infection in the CoronaVac group failed to protect against the Omicron variant.Interpretations: The current vaccines do not induce as strong neutralising antibodies with broad variant protection as infection and suggest vaccines that induce broader sterilising immunity are essential to prevent new variants emerging.Funding Information: This work was funded by MymAb Biologics Pvt. Ltd.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: All volunteers provided informed consent for the research work to be carried out.