Vaccine-induced and hybrid immunity against SARS-CoV-2 variants of concern in two cohorts in Queensland, Australia (2021-2022).

The spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main target for vaccine development, as antibodies generated against the spike protein are the most immunodominant and neutralizing against the virus. However, variants of concern (VOC), often containing multiple mutations within neutralizing epitopes, confer immune evasion of the response generated by current SARS-CoV-2 vaccines. To assess the immunogenicity and virus-neutralisation ability of antibodies induced by individual or combination of Vaxzevria (AstraZeneca: AZ) and Comirnaty (Pfizer: PZ) vaccines and of a hybrid immunity induced in people who were also infected with SARS-CoV-2, longitudinal sera samples of participants recruited through the David Serisier Research biobank (Mater Research Hospital) or at the University of Queensland were collected. ELISA with a panel of purified Spike proteins from ancestral, alpha, delta and omicron BA.1 and BA.2 VOCs showed significantly (by [~]2 to 6-fold) reduced IgG antibody titres against Spike proteins from Omicron BA.1 and BA.2 compared to ancestral strain regardless of the number of vaccinations or presence of infection. Neutralisation assays showed reduced activity against delta and omicron BA.1, BA.5 and BA.5 VOCs. However, the differences were in general less pronounced than in the ELISA assay and some were not statistically significant, particularly after four (two AZ and two PZ) vaccinations. We also generated by circular polymerase extension reaction an attenuated SARS-CoV-2 strain with deletion of all accessory genes, ORF 3, 6, 7 and 8, based on the ancestral (QLD02) virus backbone (QLD02{Delta}3678) and validated it in virus-neutralization assays with our panel of sera samples. We showed the attenuation of the QLD02{Delta}3678 virus in Vero E6 and human Caco2 cells. We demonstrated that neutralization assays with the wild-type QLD02 virus and QLD02{Delta}3678 virus were concordant, providing a safe platform for neutralisation assays in BSL2/PC2 settings.