PMID- 26761396 OWN - NLM STAT- MEDLINE DCOM- 20160706 LR - 20170602 IS - 1096-0341 (Electronic) IS - 0042-6822 (Linking) VI - 489 DP - 2016 Feb TI - Effects of modification of the HIV-1 Env cytoplasmic tail on immunogenicity of VLP vaccines. PG - 141-50 LID - S0042-6822(15)00406-7 [pii] LID - 10.1016/j.virol.2015.09.015 [doi] AB - 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. CI - Copyright (c) 2016. Published by Elsevier Inc. FAU - Vzorov, Andrei N AU - Vzorov AN AD - Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: avzorov@emory.edu. FAU - Wang, Li AU - Wang L AD - Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Chen, Jianjun AU - Chen J AD - Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Wang, Bao-Zhong AU - Wang BZ AD - Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Compans, Richard W AU - Compans RW AD - Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. LA - eng GR - AI090480/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20160104 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (AIDS Vaccines) RN - 0 (HIV Antibodies) RN - 0 (env Gene Products, Human Immunodeficiency Virus) SB - IM MH - AIDS Vaccines/administration & dosage/chemistry/genetics/immunology MH - Amino Acid Motifs MH - Animals MH - Female MH - Guinea Pigs MH - HIV Antibodies/immunology MH - HIV Infections/immunology/*prevention & control/virology MH - HIV-1/chemistry/genetics/*immunology MH - Humans MH - Immunization MH - Mice MH - Neutralization Tests MH - env Gene Products, Human Immunodeficiency Virus/administration & dosage/*chemistry/genetics/*immunology OTO - NOTNLM OT - Antibody avidity OT - Cross-clade immunization OT - Cytoplasmic tail OT - Env glycoprotein OT - HIV-1 OT - Immunogenicity OT - Neutralizing antibodies OT - Protein modification OT - Trimer stability OT - VLP vaccine EDAT- 2016/01/14 06:00 MHDA- 2016/07/07 06:00 CRDT- 2016/01/14 06:00 PHST- 2015/07/09 00:00 [received] PHST- 2015/09/23 00:00 [revised] PHST- 2015/09/24 00:00 [accepted] PHST- 2016/01/14 06:00 [entrez] PHST- 2016/01/14 06:00 [pubmed] PHST- 2016/07/07 06:00 [medline] AID - S0042-6822(15)00406-7 [pii] AID - 10.1016/j.virol.2015.09.015 [doi] PST - ppublish SO - Virology. 2016 Feb;489:141-50. doi: 10.1016/j.virol.2015.09.015. Epub 2016 Jan 4.