Cellular Immune Responses are Preserved and May Contribute to Chadox1 ChAdOx1 nCoV-19 Vaccine Effectiveness Against Infection Due to SARS-CoV-2 B·1·617·2 Delta Variant Despite Reduced Virus Neutralisation

Background: The emergence of SARS-CoV-2 variants of concern (VoC) has threatened the effectiveness of vaccination due to decreased neutralisation ability of the vaccine generated antibodies. Our objective was to assess ChAdOx1 nCoV-19 vaccine effectiveness during the massive surge from 1st April to 31stMay 2021 predominantly due to the more infectious B·1·617·2 (Delta) in India. Methods: We conducted a test-negative case-control study to assess the effectiveness of ChAdOx1 nCoV-19 vaccine. Cases were RT-PCR positive for SARS-CoV-2 infection. In addition, we tested live virus neutralisation and cellular immune responses against VoC among healthy recipients of ChAdOx1 nCoV-19 vaccine. The outcomes were effectiveness of ChAdOx1 nCoV-19 against infection and severe coronavirus disease-19, virus neutralisation effectivity and T-cell responses against the VoC among healthy vaccine recipients. Findings: Of the 2766 cases of confirmed SARS-CoV-2 infection, 3·1% were fully vaccinated compared with 7·1% of the 2377 controls giving an adjusted OR of 0·37 (95%CI 0·28, 0·48); this translated to 63·1% (95%CI 51·5, 72·1) vaccine effectiveness against SARS-CoV-2 B·1·617·2 variant, seen in 90% of the infected population as confirmed by whole-genome virus sequencing. Full vaccination prevented moderate-severe COVID-19 in 81·5% (95%CI: 9·9, 99·0). The effectiveness of single-dose vaccine was 46·2% (95%CI: 31·6, 57·7) against infection but 79·2% (95%CI: 46·1, 94·0) in preventing moderate-severe Covid-19. Among healthy vaccinated persons, plasma live virus neutralisation was 2·5-6·8 fold lower against B·1·1·7, B·1·351, B·1·617·1 and B·1·617·2 being lowest against B·1·617·2. However, T-cell responses were preserved against the recombinant mutant receptor binding domain antigens suggesting cell-mediated immune protection. Interpretation: Despite significantly reduced virus neutralisation, the effectiveness of ChAdOx1 nCoV-19 vaccine was 63% against B·1·617·2 infection and 81·5% in preventing severe disease. Spike specific T cells responses against virus variants were maintained and might contribute to immune protection following vaccination. Funding Information: Department of Biotechnology, Government of India; Council for Scientific and Industrial Research, India; Fondation Botnar. Declaration of Interests: None to declare. Ethics Approval Statement: The studies were approved by the Institute Ethics Committees of the partnering institutions.