Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S

Abstract

Background The Ad26.COV2.S vaccine was highly effective against severe–critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis. Methods We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×10 10 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe–critical Covid-19 with onset at least 14 days after administration and at least 28 days after administration in the per-protocol population. Safety and key secondary and exploratory end points were also assessed. Results Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe–critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe–critical Covid-19 (with only 4 severe–critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19–related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified. Conclusions A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe–critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722 .)

COVID-19 vaccine development: milestones, lessons and prospects

“…Increased secondary attack rate. Unknown Unknown 70.4% 261 70.2% 262 85.6% 262 1.2-fold decrease of neutralizing antibody titers 263 89.5% 264 B.1.351 (Beta) 5.2 Possible increased risk of severe disease and in-hospital mortality. Two-dose: 5.47-fold decrease of plasma neutralization titers compared to against prototype.…”

Antibody evolution to SARS-CoV-2 after single-dose Ad26.COV2.S vaccine

“…However, protection against COVID-19 infection appeared to wane over time with Ad26.COV2.S demonstrating the most prominent decrease from 75% to 60% protective efficacy 5 months after vaccination, compared to a decrease in vaccine efficacy from 95% to either 67% or 80% after BNT162b2 and mRNA-1273 vaccination, respectively, over a similar period of time ( 4 ). Loss of protection against infection was associated with lower overall levels of SARS-CoV-2 spike protein (S)–specific antibodies and plasma neutralizing activity after Ad26.COV2.S immunization compared to mRNA vaccines ( 5, 6 ).…”

Immunogenicity of an Ad26-based SARS-CoV-2 Omicron Vaccine in Naïve Mice and SARS-CoV-2 Spike Pre-immune Hamsters

“…1.351) and Delta (B.1.617.2) variants of concern (VOC) were initially thought to potentially evade vaccine elicited immunity. However, COVID-19 vaccine efficacy was largely maintained [3][4][5][6][7][8] . The Delta VOC obtained virtually worldwide dominance until it was replaced by the Omicron variant, BA.1 (initially named B.1.1.529).…”

“…Janssen developed the Ad26.COV2.S vaccine, which is a replication-incompetent human adenovirus type 26 (Ad26) vector 1 encoding a stabilized pre-fusion SARS-CoV-2 spike protein based on the Wuhan-Hu-1 isolate 2 . A phase 3 trial demonstrated that Ad26.COV2.S was 74.6% efficacious at preventing severe-critical COVID-19 3 . The Ad26.COV2.S COVID-19 vaccine was granted emergency use authorization in the US and (conditional) marketing authorization in the European Union; in more than 50 other countries.…”