The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged in late 2019 in Wuhan, China, and has led to high morbidity and mortality worldwide, with newer, more infectious variants rapidly emerging and infecting more people in several countries.
Thanks to a collaborative effort by scientists across the world, many vaccines have been developed to prevent SARS-CoV-2 infection with unprecedented speed.
One of these vaccines, the Ad26.COV2.S vaccine by Johnson & Johnson and Janssen, is a recombinant, replication-incompetent human adenovirus type 26 vector that encodes full-length SARS-CoV-2 spike protein in a prefusion-stabilized conformation.
An international randomized, controlled trial to assess the efficacy of the Ad26.COV2.S vaccine
An international, randomized, double-blind, placebo-controlled, phase 3 trial recently conducted in several countries randomly administered a single dose of Ad26.COV2.S or placebo to adult participants in a 1:1 ratio.
The trial is an ongoing, 2-year, multicenter, pivotal trial in Argentina, Chile, Brazil, Colombia, Peru, Mexico, South Africa, and the U.S.
All study participants provided written consent, and the trial followed the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Council for Harmonisation. The study is published in The New England Journal of Medicine.
The study's primary endpoints were vaccine efficacy against moderate to severe-critical COVID-19 with an onset at least 14 and 28 days post-administration among participants in the per-protocol population who tested negative for SARS-CoV-2. Safety was also assessed as part of the trial.
The Ad26.COV2.S vaccine was efficacious against severe-critical COVID-19
The per-protocol population comprised 19,630 SARS-CoV-2–negative individuals who received the Ad26.COV2.S vaccine and 19,691 participants who received placebo. The Ad26.COV2.S vaccine protected the participants against moderate to severe-critical COVID-19 with onset 14 days after administration - 116 cases in the vaccine group vs. 348 in the placebo group with an efficacy of 66.9% - and 28 days after administration - 66 cases in the vaccine group vs. 193 cases in the placebo group with an efficacy of 66.1%.
Vaccine efficacy was higher against severe-critical COVID-19 -76.7% - for onset at ≥14 days and 85.4% for onset at ≥28 days. The Ad26.COV2.S vaccine recipients who had breakthrough COVID-19 reported fewer and less severe symptoms compared to placebo recipients with COVID-19. This suggests that the disease is milder post-vaccination.
Efficacy increases through 8 weeks post-administration and did not wane for up to 15 weeks
The onset of efficacy was apparent 7 days after administration in severe–critical disease and 14 days after administration in moderate to severe–critical disease. Efficacy continued to increase through 8 weeks post administration of the vaccine, especially in the case of severe–critical COVID-19. There was no evidence of waning efficacy in the approximately 3,000 participants followed up for 11 weeks or among the 1,000 participants followed up for 15 weeks. This finding is consistent with the persistence of humoral immunity observed in a phase 1–2a trial.
Efficacy against severe–critical disease was consistently high overall and also in individual countries with sufficient cases for analysis. This is important because severe COVID-19 impacts individuals and health care systems more than mild to moderate disease.
Despite 94.5% of cases in South Africa having a sequenced virus with the 20H/501Y.V2 variant, vaccine efficacy was 52.0% against moderate to severe-critical COVID-19 with onset at least 14 days and 64.0% with onset at least 28 days after administration, respectively. Efficacy of the vaccine against severe–critical COVID-19 was 73.1% and 81.7%, respectively, for onset at least 14 and 28 days after administration.
Reactogenicity of Ad26.COV2.S was higher than that of placebo and was mild to moderate as well as transient. The serious adverse events were balanced between the two groups. There were 3 deaths in the vaccine group, and none of them were related to COVID-19. A total of 16 deaths were reported in the placebo group, and 5 of them were COVID-19–related.
The results show that a single dose of the Ad26.COV2.S vaccine offered protection against asymptomatic SARS-CoV-2 infection and symptomatic COVID-19. It was also effective against severe–critical COVID-19 disease leading to hospitalization and death. Safety was found to be similar to that in other phase 3 COVID-19 vaccine trials. Janssen Research and Development and others funded the trial.
- Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19, Jerald Sadoff, M.D., Glenda Gray, M.B., B.Ch., An Vandebosch, Ph.D., Vicky Cárdenas, Ph.D., Georgi Shukarev, M.D., Beatriz Grinsztejn, M.D., Paul A. Goepfert, M.D., Carla Truyers, Ph.D., Hein Fennema, Ph.D., Bart Spiessens, Ph.D., Kim Offergeld, M.Sc., Gert Scheper, Ph.D., Kimberly L. Taylor, Ph.D., Merlin L. Robb, M.D., John Treanor, M.D., Dan H. Barouch, M.D., Jeffrey Stoddard, M.D., Martin F. Ryser, M.D., Mary A. Marovich, M.D., Kathleen M. Neuzil, M.D., Lawrence Corey, M.D., Nancy Cauwenberghs, Ph.D., Tamzin Tanner, Ph.D., Karin Hardt, Ph.D., Javier Ruiz-Guiñazú, M.D., Mathieu Le Gars, Ph.D., Hanneke Schuitemaker, Ph.D., Johan Van Hoof, M.D., Frank Struyf, M.D., and Macaya Douoguih, M.D. for the ENSEMBLE Study Group, NEJM, DOI: 10.1056/NEJMoa2101544, https://www.nejm.org/doi/full/10.1056/NEJMoa2101544