title: Biocompatible anionic polymeric microspheres as priming delivery system for effetive HIV/AIDS Tat-based vaccines.
abstract: Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6Pcy243, vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4+ T cell depletion rate during the acute phase of infection and higher ability to resume the CD4+ T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates.
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Titti
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Maggiorella
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Ferrantelli
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sernicola
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bellino
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Collacchi
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Fanales Belasio
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Moretti
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Pavone Cossut
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Belli
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Olivieri
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Farcomeni
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Compagnoni
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Zuleika
authors.initials: Z
authors.lastname: Michelini
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Sabbatucci
authors.affiliation: Department of Environmental and Live Science, University of East Piemonte, Alessandria, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Sparnacci
authors.affiliation: I.S.O.F., Consiglio Nazionale delle Ricerche, Bologna, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Tondelli
authors.affiliation: Department of Environmental and Live Science, University of East Piemonte, Alessandria, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Laus
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology; D000818:Animals; D000838:Anions; D000917:Antibody Formation / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D016503:Drug Delivery Systems; D018604:Epitope Mapping; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007275:Injections, Intravenous; D018655:Lymphocyte Count; D008251:Macaca; D008297:Male; D008863:Microspheres; D011108:Polymers / Q000737:chemistry*; D018709:Statistics, Nonparametric; D014766:Viremia / Q000097:blood / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000838:Anions; D001672:Biocompatible Materials; D016207:Cytokines; D007074:Immunoglobulin G; D011108:Polymers; D054322:tat Gene Products, Human Immunodeficiency Virus