title: Effects of modification of the HIV-1 Env cytoplasmic tail on immunogenicity of VLP vaccines.
abstract: We investigated the effects on assembly and antigenic properties of specific modifications of the transmembrane spanning (TMS) and cytoplasmic tail (CT) domains of HIV-1 Env from a transmitted/founder (T/F) ZM53 Env glycoprotein. A construct containing a short version of the TMS domain derived from the mouse mammary tumor virus (MMTV) Env with or without a GCN4 trimerization sequence in the CT exhibited the highest levels of incorporation into VLPs and induced the highest titers of anti-Env IgG immune responses in a VLP context. Sera from guinea pigs immunized by VLPs with high Env content, and containing the CT trimerization sequence, had increased neutralization activity and antibody avidity. A cross-clade prime-boost regimen with clade B SF162 or clade C ZM53 Env DNA priming and boosting with VLPs containing modified ZM53 Env further enhanced these immune responses. The modified VLPs demonstrate improved potential as HIV-1 vaccine antigens.
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: avzorov@emory.edu.
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Vzorov
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D020816:Amino Acid Motifs; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D015483:HIV Antibodies / 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; D051379:Mice; D009500:Neutralization Tests; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: Antibody avidity; Cross-clade immunization; Cytoplasmic tail; Env glycoprotein; HIV-1; Immunogenicity; Neutralizing antibodies; Protein modification; Trimer stability; VLP vaccine