title: Vaccine focusing to cross-subtype HIV-1 gp120 variable loop epitopes.
abstract: We designed synthetic, epitope-focused immunogens that preferentially display individual neutralization epitopes targeted by cross-subtype anti-HIV V3 loop neutralizing monoclonal antibodies (mAbs). Vaccination of rabbits with these immunogens resulted in the elicitation of distinct polyclonal serum Abs that exhibit cross-subtype neutralization specificities mimicking the mAbs that guided the design. Our results prove the principle that a predictable range of epitope-specific polyclonal cross-subtype HIV-1 neutralizing Abs can be intentionally elicited in mammals by vaccination. The precise boundaries of the epitopes and conformational flexibility in the presentation of the epitopes in the immunogen appeared to be important for successful elicitation. This work may serve as a starting point for translating the activities of human broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs) into matched immunogens that can contribute to an efficacious HIV-1 vaccine.
authors.affiliation: New York University School of Medicine, Department of Biochemistry and Molecular Pharmacology, 550 First Avenue, New York, NY 10016, United States. Electronic address: Timothy.Cardozo@nyumc.org.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cardozo
authors.affiliation: University of Massachusetts Medical School, Department of Medicine, 364 Plantation Street, Lazare Research Building, Worcester, MA 01605, United States.
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.affiliation: New York University School of Medicine, Department of Biochemistry and Molecular Pharmacology, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Xunqing
authors.initials: X
authors.lastname: Jiang
authors.affiliation: New York University School of Medicine, Department of Biochemistry and Molecular Pharmacology, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Xiang-Peng
authors.initials: XP
authors.lastname: Kong
authors.affiliation: New York University School of Medicine, Department of Pathology, 550 First Avenue, New York, NY 10016, United States; Veterans Affairs Medical Center, 423 East 23rd Street, New York, NY 10010, United States.
authors.forename: Catarina
authors.initials: C
authors.lastname: Hioe
authors.affiliation: New York University School of Medicine, Department of Biochemistry and Molecular Pharmacology, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Chavdar
authors.initials: C
authors.lastname: Krachmarov
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000918:Antibody Specificity; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D008969:Molecular Sequence Data; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: Antibodies; HIV-1 vaccine; Immunofocusing; V3 loop