Ad35 and Ad26 Vaccine Vectors Induce Potent and Cross-Reactive Antibody and T-Cell Responses to Multiple Filovirus Species

Roland Zahn,Maria Grazia Pau,Jaap Goudsmit,Gert Gillisen,Jort Vellinga,Marina Koning,Esmeralda Van Der Helm,Dirk Spek,Gerrit Jan Weverling,Hanneke Schuitemaker,Ariane Rodríguez,Katarina Radošević,Jerome Custers,Anna Roos,Mo Weijtens,Gavin J D Smith

doi:10.1371/journal.pone.0044115

Roland Zahn, Maria Grazia Pau + Show 14 more

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https://doi.org/10.1371/journal.pone.0044115

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Journal: PLoS ONE	Publication Date: Dec 6, 2012
Citations: 104	License type: CC BY 4.0

Affiliation: Johnson & Johnson (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.

Highlights

Unpredictable reoccurring sporadic outbreaks of lethal filovirus associated hemorrhagic fever pose a major risk in sub Saharan Africa as they have a high human case fatality rate of 25–90% [1]
In order to obtain optimal coverage by a filovirus glycoprotein based vaccine we performed a phylogenetic analysis of all available glycoprotein amino acid sequence of all strains that caused outbreaks of hemorrhagic fever since the identification of filovirus as the causative agent in 1967 (Figure S1)
Ebola can be subdivided into Ebola Zaire, Sudan, Ivory Coast, and Bundibugyo species whereas Marburg virus glycoprotein is more homologous in sequence and cannot be grouped in distinct virus species

Summary

Introduction

Unpredictable reoccurring sporadic outbreaks of lethal filovirus associated hemorrhagic fever pose a major risk in sub Saharan Africa as they have a high human case fatality rate of 25–90% [1]. Multiple studies have shown that fruit bats, a believed source of filovirus transmission, have seroprevalence rates from 1–3% for both Ebola and Marburg viruses [3,10,11,12]. These data and the observation that lethal outbreaks have occurred more frequently in recent years [13] illustrate the urgent need for a vaccine to provide protection against all major filovirus species

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