Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox.

Adolescent Adult Antibodies, Neutralizing / blood Antibodies, Viral / blood Female Humans Male Smallpox / immunology Smallpox Vaccine / adverse effects Treatment Outcome Vaccines, Attenuated / adverse effects Vaccinia virus / immunology Young Adult

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
14 11 2019
Historique:
entrez: 14 11 2019
pubmed: 14 11 2019
medline: 23 11 2019
Statut: ppublish

Résumé

Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have considerable side effects. To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio. A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 [95% confidence interval {CI}, 1.56 to 2.40]). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.).

Sections du résumé

BACKGROUND
Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have considerable side effects.
METHODS
To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio.
RESULTS
A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 [95% confidence interval {CI}, 1.56 to 2.40]). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm
CONCLUSIONS
No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.).

Identifiants

DOI: 10.1056/NEJMoa1817307 PMID: 31722150
pubmed: 31722150
doi: 10.1056/NEJMoa1817307
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antibodies, Viral 0
Smallpox Vaccine 0
Vaccines, Attenuated 0

Banques de données

ClinicalTrials.gov
['NCT01913353']

Types de publication

Clinical Trial, Phase III Equivalence Trial Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1897-1908

Subventions

Organisme : U.S. Department of Health and Human Services
ID : HHS=100200700034C
Pays : International

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2019 Massachusetts Medical Society.

Auteurs

Phillip R Pittman (PR)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Matthew Hahn (M)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

HeeChoon S Lee (HS)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Craig Koca (C)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Nathaly Samy (N)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Darja Schmidt (D)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Joachim Hornung (J)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Heinz Weidenthaler (H)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Christopher R Heery (CR)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Thomas P H Meyer (TPH)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Günter Silbernagl (G)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Jane Maclennan (J)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

Paul Chaplin (P)

From the U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD (P.R.P., C.K.); Brian Allgood Army Community Hospital, 121st Combat Support Hospital, Yongsan, South Korea (P.R.P., M.H., H.S.L., C.K.); Bavarian Nordic, Martinsried, Germany (N.S., D.S., J.H., H.W., T.P.H.M., G.S., J.M.); Bavarian Nordic, Morrisville NC (C.R.H.); and Bavarian Nordic, Kvistgård, Denmark (P.C.).

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps neutralisants › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ADN › Infections à Poxviridae › Variole › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antiviraux › Vaccin antivariolique › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins atténués › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Virus › Virus à ADN › Poxviridae › Chordopoxvirinae › Orthopoxvirus › Virus de la vaccine › Phase 3 Efficacy Trial of Modified Vaccinia...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Jeune adulte › Phase 3 Efficacy Trial of Modified Vaccinia...