Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain
1 Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Bldg. 29B, Room 5NN22, 8800 Rockville Pike, Bethesda, MD 20892, USA
2 Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research FDA, Bethesda, MD, USA
3 Biometric Research Branch, National Cancer Institute, Rockville, MD, USA
4 NIH/NIAID, Integrated Research Facility at Fort Detrick, Frederick, MD, USA
5 Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Review, FDA, Bethesda, MD, USA
Virology Journal 2012, 9:32 doi:10.1186/1743-422X-9-32Published: 25 January 2012
The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD) would induce cross-species immunity by making more conserved regions accessible to the immune system.
To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs) bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP) that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs.
Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced.
Our findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system.