title: AIDS vaccination studies with an ex vivo feline immunodeficiency virus model: analysis of the accessory ORF-A protein and DNA as protective immunogens.
abstract: Determining which antigen must be included in AIDS vaccines to confer maximum protection is of utmost importance. In primate models, vaccines consisting of or including accessory viral proteins have yielded conflicting results. We investigated the protective potential of the accessory protein ORF-A of feline immunodeficiency virus (FIV) in cats. All three immunization strategies used (protein alone in alum adjuvant, DNA alone, or DNA prime-protein boost) clearly generated detectable immune responses. Upon challenge with ex vivo homologous FIV, ORF-A-immunized cats showed distinct enhancement of acute-phase infection relative to mock-immunized animals given alum or empty vector DNA. This effect was tentatively attributed to increased expression of the FIV receptor CD134 that was observed in the immunized cats. However, at subsequent sampling points that were continued for up to 10 months postchallenge, the average plasma viral loads of the ORF-A-immunized animals were slightly but consistently reduced relative to those of the control animals. In addition, CD4(+) T lymphocytes in the circulation system declined more slowly in immunized animals than in control animals. These findings support the contention that immunization with lentiviral accessory proteins can improve the host's ability to control virus replication and slow down disease progression but also draw attention to the fact that even simple immunogens that eventually contribute to protective activity can transiently exacerbate subsequent lentiviral infections.
authors.affiliation: Dipartimento di Patologia Sperimentale, Università di Pisa, Via San Zeno 37, I-56127 Pisa, Italy. pistello@biomed.unipi.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Pistello
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonci
authors.forename: J Norman
authors.initials: JN
authors.lastname: Flynn
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Isola
authors.forename: Elisa
authors.initials: E
authors.lastname: Zabogli
authors.forename: Valentina
authors.initials: V
authors.lastname: Camerini
authors.forename: Donatella
authors.initials: D
authors.lastname: Matteucci
authors.forename: Giulia
authors.initials: G
authors.lastname: Freer
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Mauro
authors.initials: M
authors.lastname: Bendinelli
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016466:CHO Cells; D002415:Cats; D006224:Cricetinae; D004279:DNA, Viral / Q000737:chemistry*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000378:metabolism*; D008969:Molecular Sequence Data; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D019562:Viral Load; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; C514198:ORF-A protein, feline immunodeficiency virus; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D014764:Viral Proteins