title: Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication.
abstract: Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia.
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
authors.forename: Huanbin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Andersson
authors.affiliation: Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, Denmark.
authors.forename: Emeline
authors.initials: E
authors.lastname: Ragonnaud
authors.affiliation: Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Boilesen
authors.affiliation: Department of Mathematical Sciences, University of Copenhagen, 2100, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Tolver
authors.affiliation: Department of Biology, University of Copenhagen, 2100, Denmark.
authors.forename: Benjamin Anderschou Holbech
authors.initials: BAH
authors.lastname: Jensen
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Blanchard
authors.affiliation: ReiThera, viale Città d'Europa 679, 00144 Rome, Italy; CEINGE, via Gaetano Salvatore 486, 80145 Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: ReiThera, viale Città d'Europa 679, 00144 Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.affiliation: ReiThera, viale Città d'Europa 679, 00144 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.affiliation: KEIRES, Bäumleingasse 18, CH 4051 Basel, Switzerland.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, 2200, Denmark.
authors.forename: Allan Randrup
authors.initials: AR
authors.lastname: Thomsen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, 2200, Denmark.
authors.forename: Jan Pravsgaard
authors.initials: JP
authors.lastname: Christensen
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, Denmark. Electronic address: pholst@sund.ku.dk.
authors.forename: Peter Johannes
authors.initials: PJ
authors.lastname: Holst
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015478:Antigens, Heterophile / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D015301:Retroviruses, Simian / Q000502:physiology*; D018449:SAIDS Vaccines / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control; D014779:Virus Replication / Q000502:physiology
chemical_list: D015478:Antigens, Heterophile; D018449:SAIDS Vaccines
keywords: Genetic adjuvant; Heterologous viral vectored prime-boost immunization