title: Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region.
abstract: The membrane-proximal external region (MPER) of HIV-1 gp41 is an attractive target for vaccine development. Thus, better understanding of its immunogenic properties in various structural contexts is important. We previously described the crystal structure of a trimeric protein complex named gp41-HR1-54Q, which consists of the heptad repeat regions 1 and 2 and the MPER. The protein was efficiently recognized by broadly neutralizing antibodies. Here, we describe its immunogenic properties in rabbits. The protein was highly immunogenic, especially the C-terminal end of the MPER containing 4E10 and 10E8 epitopes ((671)NWFDITNWLWYIK(683)). Although antibodies exhibited strong competition activity against 4E10 and 10E8, neutralizing activity was not detected. Detailed mapping analyses indicated that amino acid residues critical for recognition resided on faces of the alpha helix that are either opposite of or perpendicular to the epitopes recognized by 4E10 and 10E8. These results provide critical information for designing the next generation of MPER-based immunogens.
authors.affiliation: College of Veterinary Medicine, Department of Biomedical Sciences, Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, 1600 S 16th Street, Ames, IA 50011-1250, USA.
authors.forename: Habtom H
authors.initials: HH
authors.lastname: Habte
authors.affiliation: College of Veterinary Medicine, Department of Biomedical Sciences, Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, 1600 S 16th Street, Ames, IA 50011-1250, USA.
authors.forename: Saikat
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: College of Veterinary Medicine, Department of Biomedical Sciences, Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, 1600 S 16th Street, Ames, IA 50011-1250, USA.
authors.forename: Heliang
authors.initials: H
authors.lastname: Shi
authors.affiliation: College of Veterinary Medicine, Department of Biomedical Sciences, Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, 1600 S 16th Street, Ames, IA 50011-1250, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Qin
authors.affiliation: College of Veterinary Medicine, Department of Biomedical Sciences, Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, 1600 S 16th Street, Ames, IA 50011-1250, USA. Electronic address: mcho@iastate.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cho
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D020816:Amino Acid Motifs; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D011817:Rabbits
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41
keywords: HIV-1; Immunogenicity; MPER; Rabbit; Vaccine; gp41