1. Selection and immune recognition of HIV-1 MPER mimotopes.
- Author
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Wieczorek L, Peachman K, Steers N, Schoen J, Rao M, Polonis V, and Rao V
- Subjects
- AIDS Vaccines administration & dosage, Amino Acid Sequence, Animals, Antibodies, Monoclonal biosynthesis, Antibodies, Neutralizing biosynthesis, Antibody Specificity, Antigens, Viral chemistry, Antigens, Viral immunology, Antigens, Viral metabolism, Binding, Competitive, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Epitopes immunology, Epitopes metabolism, Female, HIV Envelope Protein gp41 immunology, HIV Envelope Protein gp41 metabolism, HIV Infections immunology, HIV Infections virology, HIV-1 drug effects, HIV-1 genetics, HIV-2 drug effects, HIV-2 genetics, Humans, Immunity, Humoral drug effects, Immunization methods, Mice, Mice, Inbred BALB C, Peptide Library, Peptides chemistry, Peptides immunology, Peptides metabolism, Protein Binding, Epitopes chemistry, HIV Antibodies biosynthesis, HIV Envelope Protein gp41 chemistry, HIV Infections prevention & control, HIV-1 immunology, HIV-2 immunology
- Abstract
The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by several neutralizing antibodies (NAbs) and is of interest for vaccine design. In this study, we identified novel MPER peptide mimotopes and evaluated their reactivity with HIV + plasma antibodies to characterize the diversity of the immune responses to MPER during natural infection. We utilized phage display technology to generate novel mimotopes that fit antigen-binding sites of MPER NAbs 4E10, 2F5 and Z13. Plasma antibodies from 10 HIV + patients were mapped by phage immunoprecipitation, to identify unique patient MPER binding profiles that were distinct from, and overlapping with, those of MPER NAbs. 4E10 mimotope binding profiles correlated with plasma neutralization of HIV-2/HIV-1 MPER chimeric virus, and with overall plasma neutralization breadth and potency. When administered as vaccines, 4E10 mimotopes elicited low titer NAb responses in mice. HIV mimotopes may be useful for detailed analysis of plasma antibody specificity., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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