title: HIV-1 Tat-coated nanoparticles result in enhanced humoral immune responses and neutralizing antibodies compared to alum adjuvant.
abstract: HIV-1 Tat has been identified as an attractive target for vaccine development and is currently under investigation in clinical trials as both a therapeutic and preventative vaccine for HIV-1. It is well known that protein based vaccines produce poor immune responses by themselves and therefore require adjuvants to enhance immune responses. We have previously reported on the use of anionic nanoparticles (NPs) for enhancing cellular and humoral immune responses to Tat (1-72). The purpose of this study was to further evaluate the immune response of HIV-1 Tat (1-72) coated on anionic nanoparticles compared to alum using various doses of Tat (1-72). Nanoparticles were effective at generating comparable antibody titers at both 1 and 5 microg doses of Tat (1-72), whereas the antibody titers significantly decreased at the lower dose of Tat (1-72) using alum. Anti-sera from Tat (1-72) immunized mice reacted greatest to the N-terminal and basic regions of Tat, with the NP groups showing stronger reactivity to these regions compared to alum. Moreover, the anti-sera from all Tat (1-72) immunized groups contained Tat-neutralizing antibodies and were able to significantly inhibit Tat-mediated long terminal repeat (LTR) transactivation.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
authors.forename: Jigna
authors.initials: J
authors.lastname: Patel
authors.forename: David
authors.initials: D
authors.lastname: Galey
authors.forename: Julia
authors.initials: J
authors.lastname: Jones
authors.forename: Phillip
authors.initials: P
authors.lastname: Ray
authors.forename: Jerold G
authors.initials: JG
authors.lastname: Woodward
authors.forename: Avi
authors.initials: A
authors.lastname: Nath
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mumper
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D018604:Epitope Mapping; D005260:Female; D015696:Gene Products, tat / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D016325:HIV Long Terminal Repeat; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures; D009500:Neutralization Tests; D015533:Transcriptional Activation
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D015696:Gene Products, tat; D015483:HIV Antibodies; C421254:human immunodeficiency virus type 1 Tat vaccine; C041524:aluminum sulfate