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New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model

BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalen...

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Autores principales: Limbach, Keith, Stefaniak, Maureen, Chen, Ping, Patterson, Noelle B., Liao, Grant, Weng, Shaojie, Krepkiy, Svetlana, Ekberg, Greg, Torano, Holly, Ettyreddy, Damodar, Gowda, Kalpana, Sonawane, Sharvari, Belmonte, Arnel, Abot, Esteban, Sedegah, Martha, Hollingdale, Michael R., Moormann, Ann, Vulule, John, Villasante, Eileen, Richie, Thomas L., Brough, Douglas E., Bruder, Joseph T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496260/
https://www.ncbi.nlm.nih.gov/pubmed/28673287
http://dx.doi.org/10.1186/s12936-017-1911-z
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author Limbach, Keith
Stefaniak, Maureen
Chen, Ping
Patterson, Noelle B.
Liao, Grant
Weng, Shaojie
Krepkiy, Svetlana
Ekberg, Greg
Torano, Holly
Ettyreddy, Damodar
Gowda, Kalpana
Sonawane, Sharvari
Belmonte, Arnel
Abot, Esteban
Sedegah, Martha
Hollingdale, Michael R.
Moormann, Ann
Vulule, John
Villasante, Eileen
Richie, Thomas L.
Brough, Douglas E.
Bruder, Joseph T.
author_facet Limbach, Keith
Stefaniak, Maureen
Chen, Ping
Patterson, Noelle B.
Liao, Grant
Weng, Shaojie
Krepkiy, Svetlana
Ekberg, Greg
Torano, Holly
Ettyreddy, Damodar
Gowda, Kalpana
Sonawane, Sharvari
Belmonte, Arnel
Abot, Esteban
Sedegah, Martha
Hollingdale, Michael R.
Moormann, Ann
Vulule, John
Villasante, Eileen
Richie, Thomas L.
Brough, Douglas E.
Bruder, Joseph T.
author_sort Limbach, Keith
collection PubMed
description BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors. RESULTS: The seroprevalence of GC44, GC45 and GC46 is very low, and the three vectors are not efficiently neutralized by human sera from Kenya and Ghana, two countries where malaria is endemic. In mice, a single administration of GC44, GC45 and GC46 vectors expressing a murine malaria gene, Plasmodium yoelii circumsporozoite protein (PyCSP), induced robust PyCSP-specific T cell and antibody responses that were at least as high as a comparable HuAd5-PyCSP vector. Efficacy studies in a murine malaria model indicated that a prime-boost regimen with DNA-PyCSP and GC-PyCSP vectors can protect mice against a malaria challenge. Moreover, these studies indicated that a DNA-GC46-PyCSP vaccine regimen was significantly more efficacious than a DNA-HuAd5-PyCSP regimen. CONCLUSION: These data suggest that these gorilla-based adenovectors have key performance characteristics for an effective malaria vaccine. The superior performance of GC46 over HuAd5 highlights its potential for clinical development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1911-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-54962602017-07-05 New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model Limbach, Keith Stefaniak, Maureen Chen, Ping Patterson, Noelle B. Liao, Grant Weng, Shaojie Krepkiy, Svetlana Ekberg, Greg Torano, Holly Ettyreddy, Damodar Gowda, Kalpana Sonawane, Sharvari Belmonte, Arnel Abot, Esteban Sedegah, Martha Hollingdale, Michael R. Moormann, Ann Vulule, John Villasante, Eileen Richie, Thomas L. Brough, Douglas E. Bruder, Joseph T. Malar J Research BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors. RESULTS: The seroprevalence of GC44, GC45 and GC46 is very low, and the three vectors are not efficiently neutralized by human sera from Kenya and Ghana, two countries where malaria is endemic. In mice, a single administration of GC44, GC45 and GC46 vectors expressing a murine malaria gene, Plasmodium yoelii circumsporozoite protein (PyCSP), induced robust PyCSP-specific T cell and antibody responses that were at least as high as a comparable HuAd5-PyCSP vector. Efficacy studies in a murine malaria model indicated that a prime-boost regimen with DNA-PyCSP and GC-PyCSP vectors can protect mice against a malaria challenge. Moreover, these studies indicated that a DNA-GC46-PyCSP vaccine regimen was significantly more efficacious than a DNA-HuAd5-PyCSP regimen. CONCLUSION: These data suggest that these gorilla-based adenovectors have key performance characteristics for an effective malaria vaccine. The superior performance of GC46 over HuAd5 highlights its potential for clinical development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1911-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-07-03 /pmc/articles/PMC5496260/ /pubmed/28673287 http://dx.doi.org/10.1186/s12936-017-1911-z Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Limbach, Keith
Stefaniak, Maureen
Chen, Ping
Patterson, Noelle B.
Liao, Grant
Weng, Shaojie
Krepkiy, Svetlana
Ekberg, Greg
Torano, Holly
Ettyreddy, Damodar
Gowda, Kalpana
Sonawane, Sharvari
Belmonte, Arnel
Abot, Esteban
Sedegah, Martha
Hollingdale, Michael R.
Moormann, Ann
Vulule, John
Villasante, Eileen
Richie, Thomas L.
Brough, Douglas E.
Bruder, Joseph T.
New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
title New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
title_full New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
title_fullStr New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
title_full_unstemmed New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
title_short New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
title_sort new gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496260/
https://www.ncbi.nlm.nih.gov/pubmed/28673287
http://dx.doi.org/10.1186/s12936-017-1911-z
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