Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
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Ad35 and Ad26 Vaccine Vectors Induce Potent and Cross-Reactive Antibody and T-Cell Responses to Multiple Filovirus Species
Roland Zahn, Gert Gillisen, Anna Roos, Marina Koning, Esmeralda van der Helm, Dirk Spek, Mo Weijtens, Maria Grazia Pau, Katarina Rado?ević, Gerrit Jan Weverling, Jerome Custers, Jort Vellinga, Hanneke Schuitemaker, Jaap Goudsmit, Ariane Rodr?guez<SUP>*</SUP>
<SUP></SUP>
Crucell Holland BV, Leiden, The Netherlands
Abstract
Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35) was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP) if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,), two Marburg strains (Marburg Angola and Marburg Ravn) and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26?Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years.
Citation: Zahn R, Gillisen G, Roos A, Koning M, van der Helm E, et al. (2012) Ad35 and Ad26 Vaccine Vectors Induce Potent and Cross-Reactive Antibody and T-Cell Responses to Multiple Filovirus Species. PLoS ONE 7(12): e44115. doi:10.1371/journal.pone.0044115
Editor: Gavin J. D. Smith, Duke-NUS Graduate Medical School, Singapore
Received: December 1, 2011; Accepted: July 31, 2012; Published: December 6, 2012
Copyright: ? 2012 Zahn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800056C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors state that they have a financial interest. The authors are employees of Crucell Holland BV. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
* E-mail: Ariane.Rodriquez@crucell.com
-Roland Zahn, Gert Gillisen, Anna Roos, Marina Koning, Esmeralda van der Helm, Dirk Spek, Mo Weijtens, Maria Grazia Pau, Katarina Rado?ević, Gerrit Jan Weverling, Jerome Custers, Jort Vellinga, Hanneke Schuitemaker, Jaap Goudsmit, Ariane Rodr?guez<SUP>*</SUP>
<SUP></SUP>
Crucell Holland BV, Leiden, The Netherlands
Abstract
Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35) was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP) if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,), two Marburg strains (Marburg Angola and Marburg Ravn) and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26?Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years.
Citation: Zahn R, Gillisen G, Roos A, Koning M, van der Helm E, et al. (2012) Ad35 and Ad26 Vaccine Vectors Induce Potent and Cross-Reactive Antibody and T-Cell Responses to Multiple Filovirus Species. PLoS ONE 7(12): e44115. doi:10.1371/journal.pone.0044115
Editor: Gavin J. D. Smith, Duke-NUS Graduate Medical School, Singapore
Received: December 1, 2011; Accepted: July 31, 2012; Published: December 6, 2012
Copyright: ? 2012 Zahn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800056C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors state that they have a financial interest. The authors are employees of Crucell Holland BV. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
* E-mail: Ariane.Rodriquez@crucell.com
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