title: Human Rhinovirus Presenting 4E10 Epitope of HIV-1 MPER Elicits Neutralizing Antibodies in Human ICAM-1 Transgenic Mice.
abstract: Attempts at eliciting neutralizing antibodies against human immunodeficiency virus (HIV)-1 have generally failed. Computationally designed epitope-scaffold platforms allow transplantation of structural epitopes to scaffold proteins. Human rhinovirus (HRV) allows such engrafting of HIV-1 epitopes on the surface scaffold proteins. However, since HRV infects only humans and great apes, the efficacy of chimeric HRV-based live viral vaccines is difficult to assess in animal models. Here, we used human ICAM-1 transgenic (hICAM-1 Tg) mice that support productive HRV infection to assess the efficacy of chimeric HRV expressing the HIV-1 membrane proximal external region (MPER) epitope, 4E10. Intranasal immunization with chimeric HRV in transgenic mice effectively induced antibodies that recognized 4E10 peptide as well as HIV-1 Env trimer. Importantly, the immunized mouse sera were able to neutralize HIV strains including those belonging to clades B and C. Moreover, intranasal immunization could bypass pre-existing immunity to HRV. Thus, chimeric HRV appears to provide a viable vaccine vehicle for HIV-1 immunization in humans.
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yi
authors.affiliation: Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, St Paul, Minnesota, USA.
authors.forename: Xiongying
authors.initials: X
authors.lastname: Tu
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Bharaj
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
authors.forename: Junli
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
authors.forename: Premlata
authors.initials: P
authors.lastname: Shankar
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D004195:Disease Models, Animal; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D012229:Rhinovirus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1; D018799:Intercellular Adhesion Molecule-1