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Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain

Wu Ou1, Josie Delisle1, Jerome Jacques2, Joanna Shih3, Graeme Price1, Jens H Kuhn4, Vivian Wang5, Daniela Verthelyi5, Gerardo Kaplan2 and Carolyn A Wilson1*

Author Affiliations

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

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Virology Journal 2012, 9:32  doi:10.1186/1743-422X-9-32

Published: 25 January 2012

Abstract

Background

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.

Methods

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.

Results

Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced.

Conclusion

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.

Keywords:
Ebola; Ebolavirus; Envelope glycoprotein; Filovirus; Mucin-like domain; Retrovirus; Virus-like particles; DNA vaccine