Selection and immune recognition of HIV-1 MPER mimotopes

Lindsay Wieczorek; Kristina Peachman; Nicholas Steers; Jesse Schoen; Mangala Rao; Victoria Polonis; Venigalla Rao

doi:10.1016/j.virol.2020.06.016

Selection and immune recognition of HIV-1 MPER mimotopes

Virology. 2020 Nov:550:99-108. doi: 10.1016/j.virol.2020.06.016. Epub 2020 Sep 19.

Authors

Lindsay Wieczorek¹, Kristina Peachman², Nicholas Steers², Jesse Schoen², Mangala Rao³, Victoria Polonis³, Venigalla Rao⁴

Affiliations

¹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA; Catholic University of America, 620 Michigan Ave NE, Washington, DC, 20064, USA.
² U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA.
³ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
⁴ Catholic University of America, 620 Michigan Ave NE, Washington, DC, 20064, USA. Electronic address: rao@cua.edu.

PMID: 32980676
DOI: 10.1016/j.virol.2020.06.016

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.

Keywords: Biopanning; Epitope mapping; HIV-1; Membrane proximal external region; Mimotopes; Neutralizing antibodies; Phage display.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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 / chemistry*
Epitopes / immunology
Epitopes / metabolism
Female
HIV Antibodies / biosynthesis*
HIV Envelope Protein gp41 / chemistry*
HIV Envelope Protein gp41 / immunology
HIV Envelope Protein gp41 / metabolism
HIV Infections / immunology
HIV Infections / prevention & control*
HIV Infections / virology
HIV-1 / drug effects
HIV-1 / genetics
HIV-1 / immunology*
HIV-2 / drug effects
HIV-2 / genetics
HIV-2 / immunology*
Humans
Immunity, Humoral / drug effects
Immunization / methods
Mice
Mice, Inbred BALB C
Peptide Library
Peptides / chemistry
Peptides / immunology
Peptides / metabolism
Protein Binding

Substances

AIDS Vaccines
Antibodies, Monoclonal
Antibodies, Neutralizing
Antigens, Viral
Epitopes
HIV Antibodies
HIV Envelope Protein gp41
Peptide Library
Peptides

Grants and funding

R01 AI102725/AI/NIAID NIH HHS/United States