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Biology subjects

Abelson, D.

Publications and source records attributed to Abelson, D..

2 recordsLinked to original sources

A single-dose recombinant rVSVΔG-CCHFV-GPC vaccine protects nonhuman primates against heterologous Crimean-Congo hemorrhagic fever virus challenge

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread tickborne virus with potential to cause lethal disease in humans. Countermeasure research for CCHFV has been hindered by the lack of a preclinical model that closely recapitulates human disease in an immunocompetent species. Recent reports of experimental CCHFV infection of cynomolgus macaques indicate these animals exhibit disease reflective of that observed in humans. Here, we assessed the ability of a replication competent, recombinant vesicular stomatitis virus (rVSV) vector encoding CCHFV structural glycoproteins (rVSV-CCHFV-GPC) from a Clade III isolate to prevent disease in cynomolgus macaques after challenge with a Clade V isolate of CCHFV and demonstrate that a single vaccination dose is potently immunogenic and reduced viremia and inflammatory biomarker circulation when compared with unvaccinated controls. Importantly, humoral responses to CCHFV glycoproteins in vaccinated macaques were similar to those observed in human CCHF survivors. This study further supports that a rVSV expressing only the CCHFV-GPC has the potential to serve as a vaccine platform against CCHFV infections.

microbiology↗

Crimean-Congo Hemorrhagic Fever Survivors Elicit Protective Non-Neutralizing Antibodies that Target 11 Overlapping Regions on Viral Glycoprotein GP38

Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, unique to Nairoviridae, is a target of protective antibodies, but extensive mapping of the human antibody response to GP38 has not been previously performed. Here, we isolated 188 GP38-specific antibodies from human survivors of infection. Competition experiments showed that these antibodies bind across five distinct antigenic sites, encompassing eleven overlapping regions. Additionally, we reveal structures of GP38 bound with nine of these antibodies targeting different antigenic sites. Although GP38-specific antibodies were non-neutralizing, several antibodies were found to have protection equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and inform the development of broadly effective CCHFV antibody therapeutics.

immunology↗