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

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.

• Authors: Yang Liu, Baozeng Sun, Jingyu Pan, Yuancai Feng, Wei Ye, Jiahao Xu, Mingfu Lan, Hao Sun, Xiyang Zhang, Yuanjie Sun, Shuya Yang, Jingqi Shi, Fanglin Zhang, Linfeng Cheng, Dongbo Jiang, Kun Yang
• Journal: Antiviral research (Antiviral Res) Vol. 193 Pg. 105141 (09 2021) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 34274417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Ebola Vaccines
• Glycoproteins
• Lysosomal Membrane Proteins
• Recombinant Fusion Proteins
• Vaccines, DNA
• Vaccines, Synthetic

Topics

• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• BALB 3T3 Cells
• Ebola Vaccines (administration & dosage, adverse effects, genetics, immunology)
• Ebolavirus (genetics, immunology)
• Female
• Glycoproteins (genetics, immunology)
• Hemorrhagic Fever, Ebola (immunology, prevention & control)
• Humans
• Lysosomal Membrane Proteins (genetics, immunology)
• Mice
• Neutralization Tests
• Recombinant Fusion Proteins (genetics, immunology)
• Vaccines, DNA (administration & dosage, adverse effects, immunology)
• Vaccines, Synthetic (administration & dosage, adverse effects, genetics, immunology)