Construction and evaluation of DNA vaccine encoding Ebola virus glycoprotein fused with lysosome-associated membrane protein

Antiviral Res. 2021 Jul 16;193:105141. doi: 10.1016/j.antiviral.2021.105141. Online ahead of print.

Abstract

Ebola virus (EBOV) of the genus Ebolavirus belongs to the family Filoviridae, which cause disease in both humans and non-human primates. Zaire Ebola virus accounts for the highest fatality rate, reaching 90%. Considering that EBOV has a high infection and fatality rate, the development of a highly effective vaccine has become a top public health priority. Glycoprotein (GP) plays a critical role during infection and protective immune responses. Herein, we developed an EBOV GP recombinant DNA vaccine that targets the major histocompatibility complex (MHC) class II compartment by fusing with lysosomal-associated membrane protein 1 (LAMP1). Through lysosome trafficking and antigen presentation transferring, the LAMP1 targeting strategy successfully improved both humoral and cellular EBOV-GP-specific immune responses. After three consecutive immunizations, the serum antibody titers, especially the neutralizing activity of mice immunized with the pVAX-LAMP/GPEBO vaccine were significantly higher than those of the other groups. Antigen-specific T cells showed positive activity against three dominant peptides, EAAVSHLTTLATIST, IGEWAFWETKKNLTR, and ELRTFSILNRKAIDF, with high affinity for MHC class II molecules predicted by IEDB-recommended. Preliminary safety observation denied histological alterations. DNA vaccine candidate pVAX-LAMP/GPEBO shows promise against Ebola epidemic and further evaluation is guaranteed.

Keywords: DNA vaccine; Ebola virus disease (EVD); Lysosome-associated membrane protein 1 (LAMP1); MHC-II trafficking; T cell epitope; Zaire Ebola virus.