Demonstration of Cross-Protective Vaccine Immunity against an Emerging Pathogenic Ebolavirus Species

Lisa E Hensley,Daphne Stanley,Nancy J Sullivan,Clement Asiedu,Michael Bailey,Anna N Honko,Thomas G Ksiazek,Stuart T Nichol,Peter B Jahrling,Sabue Mulangu,Pierre E Rollin,Joshua Johnson,Richard A Koup,Giulia Fabozzi,Mario Roederer,Victoria Wahl-Jensen

doi:10.1371/journal.ppat.1000904

Abstract

A major challenge in developing vaccines for emerging pathogens is their continued evolution and ability to escape human immunity. Therefore, an important goal of vaccine research is to advance vaccine candidates with sufficient breadth to respond to new outbreaks of previously undetected viruses. Ebolavirus (EBOV) vaccines have demonstrated protection against EBOV infection in nonhuman primates (NHP) and show promise in human clinical trials but immune protection occurs only with vaccines whose antigens are matched to the infectious challenge species. A 2007 hemorrhagic fever outbreak in Uganda demonstrated the existence of a new EBOV species, Bundibugyo (BEBOV), that differed from viruses covered by current vaccine candidates by up to 43% in genome sequence. To address the question of whether cross-protective immunity can be generated against this novel species, cynomolgus macaques were immunized with DNA/rAd5 vaccines expressing ZEBOV and SEBOV glycoprotein (GP) prior to lethal challenge with BEBOV. Vaccinated subjects developed robust, antigen-specific humoral and cellular immune responses against the GP from ZEBOV as well as cellular immunity against BEBOV GP, and immunized macaques were uniformly protected against lethal challenge with BEBOV. This report provides the first demonstration of vaccine-induced protective immunity against challenge with a heterologous EBOV species, and shows that Ebola vaccines capable of eliciting potent cellular immunity may provide the best strategy for eliciting cross-protection against newly emerging heterologous EBOV species.

Highlights

The Ebolavirus genus of the family Filoviridae was thought previously to consist of four species, ZEBOV, SEBOV, Reston (REBOV), and Cote d’Ivoire (CIEBOV) [1]
Immunization of cynomolgus macaques with DNA/rAd It has been demonstrated previously that nonhuman primates (NHP) immunized with a vaccine consisting of EBOV GP DNA followed by boosting with recombinant adenovirus serotype 5 (rAd5) GP were uniformly protected when challenged with a lethal dose of wild-type ZEBOV, Mayinga strain [6]
Sequence divergence between genes coding for BEBOV GP and the inserts contained within the previously used vaccine is substantial, homology is displayed within the N- and C-terminal regions of GP that contain structural elements critical for virus replication [13]

Summary

Introduction

The Ebolavirus genus of the family Filoviridae was thought previously to consist of four species, ZEBOV, SEBOV, Reston (REBOV), and Cote d’Ivoire (CIEBOV) [1]. In addition to rAd vaccines, other viral-vectored and virus-like particle (VLP) vaccines have exhibited protective efficacy against EBOV infection in NHP [8,9,10]. Though each of these vaccines generates potent immune responses in NHP, protection is achieved only when the vaccine immunogen and the EBOV species used for infectious challenge are matched, and data show a lack of cross protection against antigens not contained in the vaccine [8], suggesting that existing vaccines may not provide coverage against newly emerging EBOV species

Methods

Results

Conclusion