title: Immunofocusing using conformationally constrained V3 peptide immunogens improves HIV-1 neutralization.
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.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Moseri
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel; DST-INSPIRE Faculty, Panjab University, Chandigarh 160014, India(1).
authors.forename: Eshu
authors.initials: E
authors.lastname: Sinha
authors.affiliation: 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).
authors.forename: Henni
authors.initials: H
authors.lastname: Zommer
authors.affiliation: Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, NY 10314, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Arshava
authors.affiliation: 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.
authors.forename: Fred
authors.initials: F
authors.lastname: Naider
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: Jacob.Anglister@weizmann.ac.il.
authors.forename: Jacob
authors.initials: J
authors.lastname: Anglister
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011817:Rabbits
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: HIV vaccine; Immunofocusing; Neutralizing antibodies; V3; gp120