Randomised double-blinded placebo-controlled trial (Orange)
Assessment of the safety and efficacy of vaccines against the SARS-CoV-2 in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. In this article the authors conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with HIV in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5×1010 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (COVID-19) more than 14 days after the second dose. Between June 24 and November 9, 2020, HIV-negative adults (median age, 30 years) were enrolled; 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate COVID-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], −49.9 to 59.8). Among the 42 participants with COVID-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, −76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups.
The authors concluded that a two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate COVID-19 due to the B.1.351 variant.
Madhi SA, et al. Efficacy of the ChAdOx1 nCoV-19 COVID-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 Mar 16. doi: 10.1056/NEJMoa2102214.