title: Rhesus immune responses to SIV Gag expressed by recombinant BCG vectors are independent from pre-existing mycobacterial immunity.
abstract: BACKGROUND
  A recombinant Mycobacterium bovis BCG (rBCG) vector expressing HIV transgenes is an attractive candidate as a dual vaccine against HIV and TB. However, pre-existing immune responses to mycobacteria may influence immune responses to rBCG. We analyzed data from a rhesus rBCG trial to determine the effect of pre-existing mycobacterial immune responses on the vaccine-induced responses to the vector and expressed transgene.
  
  
  METHODS
  Indian-origin rhesus macaques were primed with rBCG expressing simian immunodeficiency virus (SIV) Gag and boosted with attenuated vaccinia NYVAC gag-pol. Mycobacteria responses were measured by Mycobacterium tuberculosis (Mtb) purified protein derivative (PPD) interferon-γ ELISpot and Mtb whole cell lysate (WCL) ELISA. SIV Gag responses were measured by SIV Gag ELISpot and by p11C tetramer binding.
  
  
  RESULTS
  Baseline Mtb PPD ELISpot responses and Mtb WCL antibody responses in rhesus macaques overlapped those in human populations. Cellular and antibody responses boosted sharply 4 weeks after rBCG vaccination. Mtb WCL antibody titers at 4 weeks correlated with baseline titers. Primates vaccinated with rBCG developed strong SIV Gag ELISpot and p11C tetramer responses after rBCG prime and NYVAC boost. There were no correlations between the pre-existing mycobacterial immune responses and the SIV Gag T cell responses after vaccination.
  
  
  CONCLUSIONS
  Rhesus immune responses to SIV Gag expressed by rBCG vectors were independent from pre-existing anti-mycobacterial immunity. Rhesus macaques may serve as a surrogate for investigations of pre-existing anti-mycobacterial immunity in humans.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Birgit
authors.initials: B
authors.lastname: Korioth-Schmitz
authors.affiliation: Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Casey C
authors.initials: CC
authors.lastname: Perley
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Jaimie D
authors.initials: JD
authors.lastname: Sixsmith
authors.affiliation: Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Click
authors.affiliation: Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.affiliation: Duke University School of Medicine, Durham, NC 27710, United States. Electronic address: richard.frothingham@duke.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Frothingham
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D009163:Mycobacterium bovis; D015302:Simian Immunodeficiency Virus; D019076:Transgenes; D014373:Tuberculin; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D015683:Gene Products, gag; D014373:Tuberculin; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: HIV/SIV; Mycobacterium bovis BCG; Pre-existing immunity; Rhesus macaque