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Proteins mimicking epitope of HIV-1 virus neutralizing antibody induce virus-neutralizing sera in mice.
- Source :
-
EBioMedicine [EBioMedicine] 2019 Sep; Vol. 47, pp. 247-256. - Publication Year :
- 2019
-
Abstract
- Background: The development of an effective vaccine preventing HIV-1 infection is hindered by the enormous antigenic variability and unique biochemical and immunological properties of HIV-1 Env glycoprotein, the most promising target for HIV-1 neutralizing antibody. Functional studies of rare elite neutralizers led to the discovery of broadly neutralizing antibodies.<br />Methods: We employed a highly complex combinatorial protein library derived from a 5 kDa albumin-binding domain scaffold, fused with support protein of total 38 kDa, to screen for binders of broadly neutralizing antibody VRC01 paratope. The most specific binders were used for immunization of experimental mice to elicit Env-specific antibodies and to test their neutralization activity using a panel of HIV-1 clade C and B pseudoviruses.<br />Findings: Three most specific binders designated as VRA017, VRA019, and VRA177 exhibited high specificity to VRC01 antibody. Immunized mice produced Env-binding antibodies which neutralize eight of twelve HIV-1 Tier 2 pseudoviruses. Molecular modelling revealed a shape complementarity between VRA proteins and a part of VRC01 gp120 interacting surface.<br />Interpretation: This strategy based on the identification of protein replicas of broadly neutralizing antibody paratope represents a novel approach in HIV-1 vaccine development. This approach is not affected by low immunogenicity of neutralization-sensitive epitopes, variability, and unique biochemical properties of HIV-1 Env used as a crucial antigen in the majority of contemporary tested vaccines. FUND: Czech Health Research Council 15-32198A, Ministry of Health, Czech Republic.<br /> (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- AIDS Vaccines immunology
Amino Acid Sequence
Animals
Antibodies, Neutralizing blood
Antigens, Viral chemistry
Disease Models, Animal
Epitopes chemistry
HIV Antibodies blood
HIV Envelope Protein gp120 immunology
HIV Infections virology
Humans
Immunoglobulin G blood
Immunoglobulin G immunology
Mice
Models, Molecular
Protein Conformation
Antibodies, Neutralizing immunology
Antigens, Viral immunology
Epitopes immunology
HIV Antibodies immunology
HIV Infections immunology
HIV-1 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 47
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 31544770
- Full Text :
- https://doi.org/10.1016/j.ebiom.2019.07.015