Deletion of fusion peptide or destabilization of fusion core of HIV gp41 enhances antigenicity and immunogenicity of 4E10 epitope |
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Authors: | Li Jing Chen Xi Jiang Shibo Chen Ying-Hua |
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Affiliation: | a Laboratory of Immunology, Department of Biology, Tsinghua University, Beijing 100084, PR China b Beijing Key Laboratory for Protein Therapeutics, Beijing 100084, PR China c Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, NY 10065, USA |
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Abstract: | The human monoclonal antibody 4E10 against the membrane-proximal external region (MPER) of HIV-1 gp41 demonstrates broad neutralizing activity across various strains, and makes its epitope an attractive target for HIV-1 vaccine development. Although the contiguous epitope of 4E10 has been identified, attempts to re-elicit 4E10-like antibodies have failed, possibly due to the lack of proper conformation of the 4E10 epitope. Here we used pIg-tail expression system to construct a panel of eukaryotic cell-surface expression plasmids encoding the extracellular domain of gp41 with deletion of fusion peptide and/or introduction of L568P mutation that may disrupt the gp41 six-helix bundle core conformation as DNA vaccines for immunization of mice. We found that these changes resulted in significant increase of the antigenicity and immunogenicity of 4E10 epitope. This information is thus useful for rational design of vaccines targeting the HIV-1 gp41 MPER. |
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Keywords: | 4E10 epitope Antigenicity Fusion peptide gp41 Immunogenicity Six-helix bundle |
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