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

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

A New Approach for Monitoring Ebolavirus in Wild Great Apes

<div><p>Background</p><p>Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure.</p><p>Methodology/Principal findings</p><p>Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission).</p><p>Conclusions/Significance</p><p>Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%.</p></div

Prevalence of ebolavirus antibodies in gorilla fecal samples by sampling zone in the Republic of Congo (2005–2008).

<p>Numbers in parentheses are 95% Adjusted Wald confidence intervals.</p><p>DCO = Diagnostically confirmed outbreak.</p><p>NRO = No reported outbreak.</p><p>*Two uncertain western blot samples were counted as negative.</p>†<p>One uncertain western blot sample was counted as negative.</p><p>Prevalence of ebolavirus antibodies in gorilla fecal samples by sampling zone in the Republic of Congo (2005–2008).</p

Detection of ebolavirus NP antibodies in gorilla fecal samples.

<p>Fecal samples from wild gorillas were tested by enhanced chemiluminescent western blot using strips containing immobilized Ebola virus NP. Positive samples are grouped according to the two collection regions, diagnostically confirmed outbreak (DCO) and no reported outbreak (NRO). Strips from representative negative samples are shown. The approximate molecular weight of NP is indicated. An experimental cynomolgus macaque fecal sample spiked with NP-positive serum was used as a positive control (PC).</p

Sampling survey zones.

<p>Upper right panel: the region in Africa from which samples were collected. Large panel: enlargement showing collection zones; samples were collected within or adjacent to the Odzala-Kokoua National Park in western RoC near the border with Gabon and the large panel indicates the details of the fecal sample collection zones: A and B2 are fecal sampling zones using closed loop survey or line transects (green line) and B1, C and D are sampling zones by reconnaissance walk survey (triangle shapes) as described in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003143#s2" target="_blank">Materials and Methods</a>. The blue line is the Mambili River. The diagnostically confirmed outbreak region (DCO) south and west of the river is in gray with dash lines and the no reported outbreak (NRO) region north and east of the river is in gray without dash line. The border of the Odzala-Kokoua National Park is identified by a dashed gray line.</p

Confirmed human and ape Ebola virus (EBOV) infection in relation to sampling zones.

<p>Numbers in red triangles correspond to the number of great ape carcasses previously reported to be positive for EBOV infection by more than one diagnostic test, which includes antigen detection, DNA amplification or immunohistochemical staining. Red circles represent villages with recorded human EBOV outbreaks. Blue lines are rivers, and the limits of the Odzala-Kokoua National Park are shown by a dashed gray line. DCO: diagnostically confirmed outbreak region (south and west of the Mambili River). NRO: no reported outbreak region (north and east of Mambili River).</p