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Immunological correlates of protection afforded by PHV02 live, attenuated recombinant vesicular stomatitis virus vector vaccine against Nipah virus disease.
Monath, Thomas P; Nichols, Richard; Feldmann, Friederike; Griffin, Amanda; Haddock, Elaine; Callison, Julie; Meade-White, Kimberly; Okumura, Atsushi; Lovaglio, Jamie; Hanley, Patrick W; Clancy, Chad S; Shaia, Carl; Rida, Wasima; Fusco, Joan.
Afiliación
  • Monath TP; Crozet Biopharma LLC, Lexington, MA, United States.
  • Nichols R; Public Health Vaccines Inc., Cambridge, MA, United States.
  • Feldmann F; Public Health Vaccines Inc., Cambridge, MA, United States.
  • Griffin A; Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Haddock E; Laboratory of Virology, Division of Intramural Studies, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Callison J; Laboratory of Virology, Division of Intramural Studies, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Meade-White K; Laboratory of Virology, Division of Intramural Studies, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Okumura A; Laboratory of Virology, Division of Intramural Studies, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Lovaglio J; Laboratory of Virology, Division of Intramural Studies, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Hanley PW; Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Clancy CS; Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Shaia C; Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Rida W; Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States.
  • Fusco J; Biostatistics Consultant, Arlington, VA, United States.
Front Immunol ; 14: 1216225, 2023.
Article en En | MEDLINE | ID: mdl-37731485
Introduction: Immune correlates of protection afforded by PHV02, a recombinant vesicular stomatitis (rVSV) vector vaccine against Nipah virus (NiV) disease, were investigated in the African green monkey (AGM) model. Neutralizing antibody to NiV has been proposed as the principal mediator of protection against future NiV infection. Methods: Two approaches were used to determine the correlation between neutralizing antibody levels and outcomes following a severe (1,000 median lethal doses) intranasal/intratracheal (IN/IT) challenge with NiV (Bangladesh): (1) reduction in vaccine dose given 28 days before challenge and (2) challenge during the early phase of the antibody response to the vaccine. Results: Reduction in vaccine dose to very low levels led to primary vaccine failure rather than a sub-protective level of antibody. All AGMs vaccinated with the nominal clinical dose (2 × 107 pfu) at 21, 14, or 7 days before challenge survived. AGMs vaccinated at 21 days before challenge had neutralizing antibodies (geometric mean titer, 71.3). AGMs vaccinated at 7 or 14 days before challenge had either undetectable or low neutralizing antibody titers pre-challenge but had a rapid rise in titers after challenge that abrogated the NiV infection. A simple logistic regression model of the combined studies was used, in which the sole explanatory variable was pre-challenge neutralizing antibody titers. For a pre-challenge titer of 1:5, the predicted survival probability is 100%. The majority of animals with pre-challenge neutralizing titer of ≥1:20 were protected against pulmonary infiltrates on thoracic radiograms, and a majority of those with titers ≥1:40 were protected against clinical signs of illness and against a ≥fourfold antibody increase following challenge (indicating sterile immunity). Controls receiving rVSV-Ebola vaccine rapidly succumbed to NiV challenge, eliminating the innate immunity stimulated by the rVSV vector as a contributor to survival in monkeys challenged as early as 7 days after vaccination. Discussion and conclusion: It was concluded that PHV02 vaccine elicited a rapid onset of protection and that any detectable level of neutralizing antibody was a functional immune correlate of survival.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Virus Nipah / Infecciones por Henipavirus / Vacunas contra el Virus del Ébola / Estomatitis Vesicular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Virus Nipah / Infecciones por Henipavirus / Vacunas contra el Virus del Ébola / Estomatitis Vesicular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza