Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses

• Published in: The Lancet infectious diseases 2022-04, Vol.22 (4), p.473-482
• Main Authors: Thiruvengadam, Ramachandran, Awasthi, Amit, Medigeshi, Guruprasad, Bhattacharya, Sankar, Mani, Shailendra, Sivasubbu, Sridhar, Shrivastava, Tripti, Samal, Sweety, Rathna Murugesan, Deepika, Koundinya Desiraju, Bapu, Kshetrapal, Pallavi, Pandey, Rajesh, Scaria, Vinod, Kumar Malik, Praveen, Taneja, Juhi, Binayke, Akshay, Vohra, Tarini, Zaheer, Aymaan, Rathore, Deepak, Ahmad Khan, Naseem, Shaman, Heena, Ahmed, Shubbir, Kumar, Rajesh, Deshpande, Suprit, Subramani, Chandru, Wadhwa, Nitya, Gupta, Nimesh, Pandey, Anil K, Bhattacharya, Jayanta, Agrawal, Anurag, Vrati, Sudhanshu, Bhatnagar, Shinjini, Garg, Pramod Kumar
• Format: Article
• Language: English
• Subjects: Antibodies; Antibody Formation; Antigens; Biotechnology; Case studies; Case-Control Studies; CD4 antigen; CD8 antigen; ChAdOx1 nCoV-19; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 - prevention & control; COVID-19 diagnostic tests; COVID-19 Vaccines; Cytokines; Health care; Hospitals; Humans; Humoral immunity; Immune response; Immune response (cell-mediated); Immune system; Industrial research; Infections; Infectious diseases; Lymphocytes T; Medical research; Mutation; Nucleocapsids; Peptides; Polymerase chain reaction; Proteins; Research facilities; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike protein; Vaccination; Vaccine efficacy; Vaccines; Viral diseases; VOCs; Volatile organic compounds
• ISSN: 1473-3099; 1474-4457; 1474-4457
• DOI: 10.1016/S1473-3099(21)00680-0

SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination. We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-to-severe disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine. Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3·6%) were fully vaccinated compared with 168 (8·5%) of 1981 controls (adjusted OR [aOR] 0·37 [95% CI 0·28–0·48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63·1% (95% CI 51·5–72·1). 157 (6·4%) of 2451 of cases and 181 (9·1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0·54 [95% CI 0·42–0·68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46·2% (95% CI 31·6–57·7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0·19 [95% CI 0·01–0·90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81·5% (95% CI 9·9–99·0). The effectiveness of a single dose against moderate-to-severe disease was 79·2% (95% CI 46·1–94·0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0·20 [95% CI 0·06–0·54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244·7 [95% CI 151·8–394·4]), beta (B.1.351; 97·6 [61·2–155·8]), kappa (B.1.617.1;