Venue: Seminar Hall
Speaker: Dr Karnail Singh, Assistant Professor, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, USA
Title: Enhancing breadth of immune responses against pathogenic Ebolaviruses by an Ebola virus-like particle (VLP) vaccine
Abstract: Ebolaviruses are highly pathogenic viruses belonging to family Filoviridae. They are the causative agents of highly fatal Ebola virus disease (EVD). In the absence of any licensed treatment and/or vaccine, mortality rates with EVD are often very high. The devastating 20132016 Ebola outbreak in West Africa led to accelerated efforts to develop vaccines against these highly virulent viruses. A live, recombinant vesicular stomatitis virus-based vaccine (VSVZEBOV) has been deployed in outbreak settings and appears effective. Vaccines based on replication-deficient adenovirus vectors either alone or in combination with a multivalent modified vaccinia Ankara (MVA) Ebola vaccine appear promising. Both these vaccine strategies have limitations though. While pre-existing immunity against the adenovirus vectors is a challenge with adenovirus-based Ebola vaccines, VSV-ZEBOV vaccine induced serious adverse events in certain groups of vaccine recipients. These approaches may require additional boosting to extend the durability of the protective immunity. Additionally, no study has shown the ability of these vaccines to provide cross-protective immunity against all the pathogenic Ebolaviruses. We developed and tested immunogenicity of a bivalent, spherical Ebola VLP vaccine expressing glycoproteins (GPs) from Zaire (EBOV) and Sudan (SUDV) Ebolaviruses in rabbits and rhesus macaques. Immunization of rabbits produced antibodies that neutralized all known pathogenic species of Ebolaviruses and mediated antibody dependent cell-mediated cytotoxicity (ADCC) against EBOV and against the SUDV. Vaccination of rhesus macaques with bivalent Ebola VLPs elicited strong anti-Ebola humoral immune responses as evidenced by binding, neutralizing and ADCC mediating anti-Ebola antibodies. Furthermore, vaccination led to significant increase in the frequencies of activated (CD38+HLA-DR+), proliferating (Ki67+) and cytokine secreting (IFN-g+ and/or TNF+) peripheral CD4 and CD8 cells. Humoral and cell mediated immune responses were still detectable at six months after the last booster dose. Together, these results show the ability of a novel bivalent Ebola VLP vaccine to induce strong immune responses against all known pathogenic Ebolaviruses and warrants its further evaluation as a pan-Ebola vaccine.
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