ABSTRACT
BackgroundIn order to determine the immunogenicity of a single dose of the AZD1222/Covishield vaccine in a real-world situation, we assessed the immunogenicity, in a large cohort of health care workers in Sri Lanka. MethodsSARS-CoV-2 antibodies was carried out in 607 naive and 26 previously infected health care workers (HCWs) 28 to 32 days following a single dose of the vaccine. Haemagglutination test (HAT) for antibodies to the receptor binding domain (RBD) of the wild type virus, B.1.1.7, B.1.351 and the surrogate neutralization assay (sVNT) was carried out in 69 naive and 26 previously infected individuals. Spike protein (pools S1 and S2) specific T cell responses were measured by ex vivo ELISpot IFN{gamma} assays in 76 individuals. Results92.9% of previously naive HCWs seroconverted to a single dose of the vaccine, irrespective of age and gender; and ACE2 blocking antibodies were detected in 67/69 (97.1%) previously naive vaccine recipients. Although high levels of antibodies were found to the RBD of the wild type virus, the titres for B.1.1.7 and B.1.351 were lower in previously naive HCWs. Ex vivo T cell responses were observed to S1 in 63.9% HCWs and S2 in 31.9%. The ACE2 blocking titres measured by the sVNT significantly increased (p<0.0001) from a median of 54.1 to 97.9 % of inhibition, in previously infected HCWs and antibodies to the RBD for the variants B.1.1.7 and B.1.351 also significantly increased. Discussiona single dose of the AZD1222/Covishield vaccine was shown to be highly immunogenic in previously naive individuals inducing antibody levels greater than following natural infection. In infected individuals, a single dose induced very high levels of ACE2 blocking antibodies and antibodies to RBDs of SARS-CoV-2 variants of concern. FundingWe are grateful to the World Health Organization, UK Medical Research Council and the Foreign and Commonwealth Office.
ABSTRACT
Background Individuals who have not been exposed to the SARS-CoV2 virus have been shown to have T cells that respond to the virus, possibly due to the presence of cross-reactive T cell responses to other seasonal human coronaviruses (HCoVs). Such cross-reactive T cell immunity may lead to immunopathology or protection.Results To understand the influence of such cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8 + T cell epitopes, restricted through HLA-A and B alleles, which are seen in a frequency of > 10% in the Sri Lankan population. Conservation analysis was carried out for these candidate epitopes with the HCoVs, OC43, HKU1, NL63 and with the current circulating different variants of SARS-CoV2. 12/18 the candidate CD8 + T cell epitopes (binding score of ≥ 0.90), which had a high degree of homology (> 75%) with the other three HCoVs were within the NSP12 and NSP13 proteins. They were predicted to be restricted through HLA-A*2402, HLA-A*201, HLA-A*206 and HLA-B alleles B*3501. 31 candidate CD8 + T cell epitopes that were specific to SARS-CoV2 virus (< 25% homology with other HCoVs) were predominantly identified within the structural proteins (spike, envelop, membrane and nucleocapsid) and the NSP1, NSP2 and NSP3. They were predominantly restricted through HLA-B*3501 (6/31), HLA-B*4001 (6/31), HLA-B*4403(7/31) and HLA-A*2402 (8/31). The candidate CD8 + T cell epitopes that were homologous or were specific, with a binding score of ≥ 0.90, were found to be highly conserved within the SARS-CoV2 variants identified so far.Conclusions It would be crucial to understand T cell responses that associate with protection and the differences in the functionality and phenotype of epitope specific T cell responses, presented through different HLA alleles common in different geographical groups in order to understand disease pathogenesis.