Antibody and T cell responses to Sinopharm/BBIBP-CorV in naïve and previously infected individuals in Sri Lanka (preprint)

Background As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. Methods SARS-CoV-2-specific antibodies were measured in 282 individuals who were seronegative at baseline, and ACE2 receptor blocking antibodies, antibodies to the receptor binding domain (RBD) of the wild type (WT), B.1.1.7, B.1.351 and B.1.617.2, ex vivo and cultured IFNγ ELISpot assays, intracellular cytokine secretion assays and B cell ELISpot assays were carried out in a sub cohort of the vaccinees at 4 weeks and at 6 weeks (2 weeks after the second dose). Results 95% of the vaccinees seroconverted, although the seroconversion rates were significantly lower (p<0.001) in individuals >60 years (93.3%) compared to those who were 20 to 39 years (98.9%). 81.25% had ACE2 receptor blocking antibodies at 6 weeks, and there was no difference in these antibody titres in vaccine sera compared to convalescent sera (p=0.44). Vaccinees had significantly less (p<0.0001) antibodies to the RBD of WT and B.1.1.7, although there was no difference in antibodies to the RBD of B.1.351 and B.1.617.2 compared to convalescent sera. 27.7% of 46.4% of vaccinees had ex vivo IFNγ and cultured ELISpot responses respectively, and IFNγ and CD107a responses were detected by flow cytometry. Conclusions Sinopharm/BBIBP-CorV appeared to induce high seroconversion rates and induce a similar level of antibody responses against ACE2 receptor, B.1.617.2 and B.1.351 as seen following natural infection.

Genomic and epidemiological analysis of SARS-CoV-2 viruses in Sri Lanka (preprint)

Since identification of the first Sri Lankan individual with the SARS-CoV-2 in early March 2020, small clusters that occurred were largely contained until the current extensive outbreak that started in early October 2020. In order to understand the molecular epidemiology of SARS-CoV-2 in Sri Lanka, we carried out genomic sequencing overlaid on available epidemiological data. The B.1.411 lineage was most prevalent, which was established in Sri Lanka and caused outbreaks throughout the country. The estimated time of the most recent common ancestor of this lineage was 10th August 2020 (95% lower and upper bounds 6th July to 7th September), suggesting cryptic transmission may have occurred, prior to a large epidemic starting in October 2020. Returning travellers were identified with infections caused by lineage B.1.258 , as well as the more transmissible B.1.1.7 lineage. Ongoing genomic surveillance in Sri Lanka is vital as vaccine roll-out increases.

Antibody and T-cell responses to a single dose of the AZD1222/Covishield vaccine in previously SARS-CoV-2 infected and naive health care workers in Sri Lanka (preprint)

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.

Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses (preprint)

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.