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Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S.
N Engl J Med. 2022 03 03; 386(9):847-860.NEJM

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.).

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Sadoff J
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Gray G
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Vandebosch A
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Cárdenas V
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Shukarev G
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Grinsztejn B
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Goepfert PA
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Truyers C
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Van Dromme I
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Spiessens B
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Vingerhoets J
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Custers J
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Scheper G
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Robb ML
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Treanor J
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Ryser MF
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Barouch DH
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Swann E
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Marovich MA
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Neuzil KM
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Corey L
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Stoddard J
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Hardt K
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Ruiz-Guiñazú J
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Le Gars M
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Schuitemaker H
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Van Hoof J
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Struyf F
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
Douoguih M
From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, G. Shukarev, J.C., G. Scheper, M.L.G., H.S., J.V.H., M.D.); the South African Research Council, Cape Town, South Africa (G.G.); Janssen Research and Development, Beerse, Belgium (A.V., C.T., I.V.D., B.S., J.V., M.F.R., K.H., J.R.-G., F.S.); Janssen Research and Development, Spring House, PA (V.C.); Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro (B.G.); the University of Alabama at Birmingham, Birmingham (P.A.G.); Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the National Institute of Allergy and Infectious Diseases, Rockville (E.S., M.A.M.), and the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.M.N.) - all in Maryland; the Biomedical Advanced Research and Development Authority, Washington, DC (J.T.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (D.H.B.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C.); and Janssen Research and Development, Raritan, NJ (J. Stoddard).
ENSEMBLE Study Group
No affiliation info available

MeSH

Ad26COVS1AdolescentAdultCOVID-19Double-Blind MethodFollow-Up StudiesHospitalizationHumansImmunogenicity, VaccineKaplan-Meier EstimateMiddle AgedPatient AcuitySARS-CoV-2Vaccine EfficacyYoung Adult

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35139271

Clinical Trial Links

Clinical trial which this article describes

Citation

Sadoff, Jerald, et al. "Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S." The New England Journal of Medicine, vol. 386, no. 9, 2022, pp. 847-860.
Sadoff J, Gray G, Vandebosch A, et al. Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S. N Engl J Med. 2022;386(9):847-860.
Sadoff, J., Gray, G., Vandebosch, A., Cárdenas, V., Shukarev, G., Grinsztejn, B., Goepfert, P. A., Truyers, C., Van Dromme, I., Spiessens, B., Vingerhoets, J., Custers, J., Scheper, G., Robb, M. L., Treanor, J., Ryser, M. F., Barouch, D. H., Swann, E., Marovich, M. A., ... Douoguih, M. (2022). Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S. The New England Journal of Medicine, 386(9), 847-860. https://doi.org/10.1056/NEJMoa2117608
Sadoff J, et al. Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S. N Engl J Med. 2022 03 3;386(9):847-860. PubMed PMID: 35139271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S. AU - Sadoff,Jerald, AU - Gray,Glenda, AU - Vandebosch,An, AU - Cárdenas,Vicky, AU - Shukarev,Georgi, AU - Grinsztejn,Beatriz, AU - Goepfert,Paul A, AU - Truyers,Carla, AU - Van Dromme,Ilse, AU - Spiessens,Bart, AU - Vingerhoets,Johan, AU - Custers,Jerome, AU - Scheper,Gert, AU - Robb,Merlin L, AU - Treanor,John, AU - Ryser,Martin F, AU - Barouch,Dan H, AU - Swann,Edith, AU - Marovich,Mary A, AU - Neuzil,Kathleen M, AU - Corey,Lawrence, AU - Stoddard,Jeffrey, AU - Hardt,Karin, AU - Ruiz-Guiñazú,Javier, AU - Le Gars,Mathieu, AU - Schuitemaker,Hanneke, AU - Van Hoof,Johan, AU - Struyf,Frank, AU - Douoguih,Macaya, AU - ,, Y1 - 2022/02/09/ PY - 2022/2/10/pubmed PY - 2022/3/16/medline PY - 2022/2/9/entrez SP - 847 EP - 860 JF - The New England journal of medicine JO - N Engl J Med VL - 386 IS - 9 N2 - 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.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/35139271/full_citation DB - PRIME DP - Unbound Medicine ER -