title: Multimodality vaccination against clade C SHIV: partial protection against mucosal challenges with a heterologous tier 2 virus.
abstract: We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. This SHIV strain exhibits many properties of transmitted HIV-1, such as tier 2 phenotype (relatively difficult to neutralize), exclusive CCR5 tropism, and gradual disease progression in infected RMs. Since no human AIDS vaccine recipient is likely to encounter an HIV-1 strain that exactly matches the immunogens, we immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low-level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses.
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Lakhashe
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Siddappa N
authors.initials: SN
authors.lastname: Byrareddy
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Mingkui
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Bachler
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Girish
authors.initials: G
authors.lastname: Hemashettar
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Shiu-Lok
authors.initials: SL
authors.lastname: Hu
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Else
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Stock
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Vaccine Branch, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Vargas-Inchaustegui
authors.affiliation: Vaccine Branch, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Egidio Brocca
authors.initials: EB
authors.lastname: Cofano
authors.affiliation: Vaccine Branch, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.affiliation: Biology Department, Boston College, MA, USA.
authors.forename: Welkin E
authors.initials: WE
authors.lastname: Johnson
authors.affiliation: The Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA, USA.
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
authors.affiliation: ETRAV Laboratory, Faculty of Pharmacy, Aix Marseille University/CNRS, 27 BD Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: Erwann P
authors.initials: EP
authors.lastname: Loret
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rasmussen
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, USA; Southwest National Primate Research Center, San Antonio, TX, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: rruprecht@txbiomed.org.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015497:HIV-1; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D008253:Macaca mulatta / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D015302:Simian Immunodeficiency Virus; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000276:immunology; D014766:Viremia / Q000517:prevention & control; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015683:Gene Products, gag; D015693:Gene Products, nef; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: ADCC; Cellular immunity; HIV vaccine; Heterologous tier 2 virus; Rhesus monkey; SHIV-C