title: Immunological Characterization of Plant-Based HIV-1 Gag/Dgp41 Virus-Like Particles.
abstract: It is widely anticipated that a prophylactic vaccine may be needed to control the HIV/AIDS epidemic worldwide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although a recent clinical trial has shown promising results. Recent studies have focused on highly conserved domains within HIV-1 such as the membrane proximal external region (MPER) of the envelope glycoprotein, gp41. MPER has been shown to play critical roles in mucosal transmission of HIV-1, though this peptide is poorly immunogenic on its own. Here we provide evidence that plant-produced HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (Dgp41) provides an effective platform to display MPER for use as an HIV vaccine candidate. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR--a fusion of MPER and the B-subunit of cholera toxin) were investigated in BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens were elicited when systemically primed with VLPs. These responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a boosting response against Gag and gp41 when boosted with either candidate. Importantly, the VLPs also induced Gag-specific CD4 and CD8 T-cell responses. This report on the immunogenicity of plant-based Gag/Dgp41 VLPs may represent an important milestone on the road towards a broadly efficacious and inexpensive subunit vaccine against HIV-1.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.|Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Kessans
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.|Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Linhart
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.|Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Lydia R
authors.initials: LR
authors.lastname: Meador
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Kilbourne
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.|Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.|Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Brenda G
authors.initials: BG
authors.lastname: Hogue
authors.affiliation: Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.|Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Petra
authors.initials: P
authors.lastname: Fromme
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.|Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matoba
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.|Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Tsafrir S
authors.initials: TS
authors.lastname: Mor
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified / Q000378:metabolism*; D014026:Nicotiana / Q000378:metabolism*; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015700:HIV Envelope Protein gp41; D058425:Vaccines, Virus-Like Particle; D054301:gag Gene Products, Human Immunodeficiency Virus; C514787:gp41 protein, Human immunodeficiency virus 1