Immunofocusing using conformationally constrained V3 peptide immunogens improves HIV-1 neutralization

Adi Moseri; Eshu Sinha; Henni Zommer; Boris Arshava; Fred Naider; Jacob Anglister

doi:10.1016/j.vaccine.2016.11.088

Immunofocusing using conformationally constrained V3 peptide immunogens improves HIV-1 neutralization

Vaccine. 2017 Jan 5;35(2):222-230. doi: 10.1016/j.vaccine.2016.11.088. Epub 2016 Dec 7.

Authors

Adi Moseri¹, Eshu Sinha², Henni Zommer³, Boris Arshava⁴, Fred Naider⁵, Jacob Anglister⁶

Affiliations

¹ Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
² Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel; DST-INSPIRE Faculty, Panjab University, Chandigarh 160014, India(1).
³ Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel(1); University of California, San Francisco, Department of Medicine, San Francisco, CA, USA(1).
⁴ Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, NY 10314, USA.
⁵ Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, NY 10314, USA; PhD Programs in Biochemistry and Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA.
⁶ Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: Jacob.Anglister@weizmann.ac.il.

PMID: 27939012
DOI: 10.1016/j.vaccine.2016.11.088

Abstract

V3-directed antibodies are present in practically all HIV-1 infected patients and in individuals vaccinated with gp120. The levels of maternal V3-directed antibodies were recently shown to correlate with reduced mother to child transmission, and V3 IgGs were found to be a negative correlate of risk in the RV-144 human trial. mAb directed to the tip of the V3 are capable of broad neutralization of Tier-1 and some Tier-2 viruses. Here we report an immunofocusing approach using conformationally constrained V3 peptides of different lengths. Immunofocusing with short constrained V3 peptides following immunizations with long constrained V3 peptides resulted in sera with improved neutralization of Tier-1B viruses in comparison with immunizations with the long constrained peptide alone. Immunizations only with the short constrained peptide were ineffective. Our results demonstrate that immunofocusing with constrained V3 peptides of different lengths could improve the induction of HIV-1 neutralizing antibodies.

Keywords: HIV vaccine; Immunofocusing; Neutralizing antibodies; V3; gp120.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines / immunology*
Animals
Antibodies, Neutralizing / immunology*
HIV Antibodies / immunology*
HIV Antigens / immunology
HIV Envelope Protein gp120 / immunology*
HIV-1 / immunology*
Humans
Rabbits

Substances

AIDS Vaccines
Antibodies, Neutralizing
HIV Antibodies
HIV Antigens
HIV Envelope Protein gp120
gp120 protein, Human immunodeficiency virus 1