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

使用带有缺乏粘蛋白样结构域的埃博拉病毒糖蛋白的逆转录病毒样颗粒诱导埃博拉病毒跨物种免疫

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作者:Wu Ou, Josie Delisle, Jerome Jacques, Joanna Shih, Graeme Price, Jens H Kuhn, Vivian Wang, Daniela Verthelyi, Gerardo Kaplan, Carolyn A Wilson

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.

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.

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.

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