Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no...

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Main Authors: Warimwe, G, Lorenzo, G, Lopez-Gil, E, Reyes-Sandoval, A, Cottingham, M, Spencer, A, Collins, K, Dicks, M, Milicic, A, Lall, A, Furze, J, Turner, A, Hill, A, Brun, A, Gilbert, S
Format: Journal article
Language:English
Published: BioMed Central 2013
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author Warimwe, G
Lorenzo, G
Lopez-Gil, E
Reyes-Sandoval, A
Cottingham, M
Spencer, A
Collins, K
Dicks, M
Milicic, A
Lall, A
Furze, J
Turner, A
Hill, A
Brun, A
Gilbert, S
author_facet Warimwe, G
Lorenzo, G
Lopez-Gil, E
Reyes-Sandoval, A
Cottingham, M
Spencer, A
Collins, K
Dicks, M
Milicic, A
Lall, A
Furze, J
Turner, A
Hill, A
Brun, A
Gilbert, S
author_sort Warimwe, G
collection OXFORD
description BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.
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spelling oxford-uuid:4b2be378-7381-4c19-ac22-a5933abf63ba2022-03-26T15:42:02ZImmunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4b2be378-7381-4c19-ac22-a5933abf63baEnglishSymplectic Elements at OxfordBioMed Central2013Warimwe, GLorenzo, GLopez-Gil, EReyes-Sandoval, ACottingham, MSpencer, ACollins, KDicks, MMilicic, ALall, AFurze, JTurner, AHill, ABrun, AGilbert, SBACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.
spellingShingle Warimwe, G
Lorenzo, G
Lopez-Gil, E
Reyes-Sandoval, A
Cottingham, M
Spencer, A
Collins, K
Dicks, M
Milicic, A
Lall, A
Furze, J
Turner, A
Hill, A
Brun, A
Gilbert, S
Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.
title Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.
title_full Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.
title_fullStr Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.
title_full_unstemmed Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.
title_short Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.
title_sort immunogenicity and efficacy of a chimpanzee adenovirus vectored rift valley fever vaccine in mice
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