Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

Feng, Shuo; Phillips, Daniel J; White, Thomas; Sayal, Homesh; Aley, Parvinder K; Bibi, Sagida; Dold, Christina; Fuskova, Michelle; Gilbert, Sarah C; Hirsch, Ian; Humphries, Holly E; Jepson, Brett; Kelly, Elizabeth J; Plested, Emma; Shoemaker, Kathryn; Thomas, Kelly M; Vekemans, Johan; Villafana, Tonya L; Lambe, Teresa; Pollard, Andrew J; Voysey, Merryn

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.