Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783247938780135424 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5496260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT limbachkeith newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT stefaniakmaureen newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT chenping newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT pattersonnoelleb newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT liaogrant newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT wengshaojie newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT krepkiysvetlana newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT ekberggreg newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT toranoholly newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT ettyreddydamodar newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT gowdakalpana newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT sonawanesharvari newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT belmontearnel newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT abotesteban newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT sedegahmartha newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT hollingdalemichaelr newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT moormannann newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT vululejohn newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT villasanteeileen newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT richiethomasl newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT broughdouglase newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel AT bruderjosepht newgorillaadenovirusvaccinevectorsinducepotentimmuneresponsesandprotectioninamousemalariamodel |