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A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.
Regules, Jason A; Beigel, John H; Paolino, Kristopher M; Voell, Jocelyn; Castellano, Amy R; Hu, Zonghui; Muñoz, Paula; Moon, James E; Ruck, Richard C; Bennett, Jason W; Twomey, Patrick S; Gutiérrez, Ramiro L; Remich, Shon A; Hack, Holly R; Wisniewski, Meagan L; Josleyn, Matthew D; Kwilas, Steven A; Van Deusen, Nicole; Mbaya, Olivier Tshiani; Zhou, Yan; Stanley, Daphne A; Jing, Wang; Smith, Kirsten S; Shi, Meng; Ledgerwood, Julie E; Graham, Barney S; Sullivan, Nancy J; Jagodzinski, Linda L; Peel, Sheila A; Alimonti, Judie B; Hooper, Jay W; Silvera, Peter M; Martin, Brian K; Monath, Thomas P; Ramsey, W Jay; Link, Charles J; Lane, H Clifford; Michael, Nelson L; Davey, Richard T; Thomas, Stephen J.
Afiliación
  • Regules JA; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Beigel JH; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Paolino KM; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Voell J; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Castellano AR; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Hu Z; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Muñoz P; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Moon JE; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Ruck RC; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Bennett JW; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Twomey PS; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Gutiérrez RL; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Remich SA; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Hack HR; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Wisniewski ML; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Josleyn MD; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Kwilas SA; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Van Deusen N; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Mbaya OT; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Zhou Y; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Stanley DA; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Jing W; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Smith KS; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Shi M; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Ledgerwood JE; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Graham BS; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Sullivan NJ; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Jagodzinski LL; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Peel SA; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Alimonti JB; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Hooper JW; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Silvera PM; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Martin BK; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Monath TP; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Ramsey WJ; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Link CJ; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Lane HC; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Michael NL; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Davey RT; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
  • Thomas SJ; From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H
N Engl J Med ; 376(4): 330-341, 2017 01 26.
Article en En | MEDLINE | ID: mdl-25830322
ABSTRACT

BACKGROUND:

The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD.

METHODS:

We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed.

RESULTS:

The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months.

CONCLUSIONS:

This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Vacunas contra el Virus del Ébola / Ebolavirus Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Vacunas contra el Virus del Ébola / Ebolavirus Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2017 Tipo del documento: Article