Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19

Abstract

Background The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation. Methods In an international, randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned adult participants in a 1:1 ratio to receive a single dose of Ad26.COV2.S (5×10 10 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe–critical coronavirus disease 2019 (Covid-19) with an onset at least 14 days and at least 28 days after administration among participants in the per-protocol population who had tested negative for SARS-CoV-2. Safety was also assessed. Results The per-protocol population included 19,630 SARS-CoV-2–negative participants who received Ad26.COV2.S and 19,691 who received placebo. Ad26.COV2.S protected against moderate to severe–critical Covid-19 with onset at least 14 days after administration (116 cases in the vaccine group vs. 348 in the placebo group; efficacy, 66.9%; adjusted 95% confidence interval [CI], 59.0 to 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 to 74.8). Vaccine efficacy was higher against severe–critical Covid-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% against moderate to severe–critical Covid-19 with onset at least 14 days and at least 28 days after administration, respectively, and efficacy against severe–critical Covid-19 was 73.1% and 81.7%, respectively. Reactogenicity was higher with Ad26.COV2.S than with placebo but was generally mild to moderate and transient. The incidence of serious adverse events was balanced between the two groups. Three deaths occurred in the vaccine group (none were Covid-19–related), and 16 in the placebo group (5 were Covid-19–related). Conclusions A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722 .)

Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa

“…Much has been made about differences in the leading vaccine candidates and the impact of variants, such as the B.1.351 variant which eventually accounted for over 90% of SARS-CoV-2 infections in South Africa, on vaccine effectiveness. 4,15 However, we found that even with lower effectiveness than that estimated from studies, a vaccination program would still prevent the majority of COVID-19 deaths that would occur without a vaccination program. For example, decreasing vaccine effectiveness against symptomatic disease and severe/critical disease requiring hospitalization to 40% still reduced COVID-19 deaths by 65,800 (74%) compared with a scenario without vaccines.…”

“…26 In the base case, we applied characteristics of Ad26.COV2.S (Johnson & Johnson/Janssen), a single-dose vaccine for which administration in South Africa began through a phase 3b study in health care workers in February 2021. 4,27 To reflect possible implementation of other vaccines, as well as published data and uncertainties around the type of protection provided by each vaccine, we varied vaccine effectiveness against SARS-CoV-2 infection, effectiveness against symptomatic COVID-19 disease, and effectiveness against severe COVID-19 disease requiring hospitalization. We assumed that a single vaccine dose would be given and did not explicitly model a two-dose schedule.…”

“…This is a particularly urgent question given the emergence of SARS-CoV-2 variants, such as B.1.351 in South Africa, that appear to partially reduce efficacy of some vaccines. 4,[12][13][14][15] We used a microsimulation model to estimate the clinical and economic outcomes of COVID-19 vaccination programs in South Africa, examining different implementation strategies that policymakers could directly influence. Our goal was to inform vaccination program priorities in South Africa and other LMICs.…”

Quantifying the potential dominance of immune-evading SARS-CoV-2 variants in the United States

“…The three authorized vaccines in the US一produced by Pfizer-BioNTech, Moderna, and Johnson & Johnson一are highly effective for preventing symptomatic and severe disease caused by the originally identified Wuhan-1 strain (5)(6)(7). Since these vaccines target the spike (S) protein of the original strain (8), vaccine-mediated neutralizing antibodies may be less protective against newer variants with multiple spike mutations (9).…”

SARS-CoV-2 vaccines and their challenges against the variants

“…9 Johnson & Johnson's human adenovirus-vectored vaccine showed 64% protection against moderate-to-severe disease in South Africa (dominated by the B.1.351 variant) and 66% protection against moderate-to-severe disease in the USA (mainly the Wuhan-1 variant with D614G), as assessed 29 days after vaccination. 10 The Pfizer/BioNTech BNT162b2 mRNA vaccine was reported to be less effective against B.1.351 than against non-B.1.351 variants based on a small analysis of breakthrough infections that were enriched for B.1.351 in Israel. 11 The efficacy of CoronaVac/Sinovac inactivated virus vaccine in Brazil, where 75% of infections were with the P.1 variant, was estimated at around 50% against symptomatic infection.…”