Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine

N Engl J Med. 2021 May 13;384(19):1824-1835. doi: 10.1056/NEJMoa2034201. Epub 2021 Jan 13.

Abstract

Background: Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein.

Methods: In this multicenter, placebo-controlled, phase 1-2a trial, we randomly assigned healthy adults between the ages of 18 and 55 years (cohort 1) and those 65 years of age or older (cohort 3) to receive the Ad26.COV2.S vaccine at a dose of 5×1010 viral particles (low dose) or 1×1011 viral particles (high dose) per milliliter or placebo in a single-dose or two-dose schedule. Longer-term data comparing a single-dose regimen with a two-dose regimen are being collected in cohort 2; those results are not reported here. The primary end points were the safety and reactogenicity of each dose schedule.

Results: After the administration of the first vaccine dose in 805 participants in cohorts 1 and 3 and after the second dose in cohort 1, the most frequent solicited adverse events were fatigue, headache, myalgia, and injection-site pain. The most frequent systemic adverse event was fever. Systemic adverse events were less common in cohort 3 than in cohort 1 and in those who received the low vaccine dose than in those who received the high dose. Reactogenicity was lower after the second dose. Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose (geometric mean titer [GMT], 212 to 354), regardless of vaccine dose or age group, and reached 96% by day 57 with a further increase in titers (GMT, 288 to 488) in cohort 1a. Titers remained stable until at least day 71. A second dose provided an increase in the titer by a factor of 2.6 to 2.9 (GMT, 827 to 1266). Spike-binding antibody responses were similar to neutralizing-antibody responses. On day 15, CD4+ T-cell responses were detected in 76 to 83% of the participants in cohort 1 and in 60 to 67% of those in cohort 3, with a clear skewing toward type 1 helper T cells. CD8+ T-cell responses were robust overall but lower in cohort 3.

Conclusions: The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate. (Funded by Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services; COV1001 ClinicalTrials.gov number, NCT04436276.).

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / adverse effects
  • COVID-19 Vaccines / immunology*
  • Cohort Studies
  • Double-Blind Method
  • Humans
  • Immunogenicity, Vaccine*
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Ad26.COV2.S vaccine

Associated data

  • ClinicalTrials.gov/NCT04436276