title: Eliciting neutralizing antibodies with gp120 outer domain constructs based on M-group consensus sequence.
abstract: One strategy being evaluated for HIV-1 vaccine development is focusing immune responses towards neutralizing epitopes on the gp120 outer domain (OD) by removing the immunodominant, but non-neutralizing, inner domain. Previous OD constructs have not elicited strong neutralizing antibodies (nAbs). We constructed two immunogens, a monomeric gp120-OD and a trimeric gp120-OD×3, based on an M group consensus sequence (MCON6). Their biochemical and immunological properties were compared with intact gp120. Results indicated better preservation of critical neutralizing epitopes on gp120-OD×3. In contrast to previous studies, our immunogens induced potent, cross-reactive nAbs in rabbits. Although nAbs primarily targeted Tier 1 viruses, they exhibited significant breadth. Epitope mapping analyses indicated that nAbs primarily targeted conserved V3 loop elements. Although the potency and breadth of nAbs were similar for all three immunogens, nAb induction kinetics indicated that gp120-OD×3 was superior to gp120-OD, suggesting that gp120-OD×3 is a promising prototype for further gp120 OD-based immunogen development.
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States; Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Yali
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States; Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Marisa
authors.initials: M
authors.lastname: Banasik
authors.affiliation: Case Western Reserve University, Department of Physiology and Biophysics, School of Medicine, Cleveland, Ohio 44106, United States.
authors.forename: SoonJeung
authors.initials: S
authors.lastname: Kim
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease & Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Adam
authors.initials: A
authors.lastname: Penn-Nicholson
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States; Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Habtom H
authors.initials: HH
authors.lastname: Habte
authors.affiliation: Department of Surgery, Duke University, Durham, NC 27710, United States.
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: Department of Surgery, Duke University, Durham, NC 27710, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Department of Statistics, Iowa State University, Ames, IA 50011, United States; Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States; Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, Ames, IA 50011, United States. Electronic address: mcho@iastate.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cho
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D016384:Consensus Sequence; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D011817:Rabbits
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: HIV-1; Neutralizing antibody; Outer domain; V3; Vaccine; gp120