title: Recombinant Mycobacterium bovis bacillus Calmette-Guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques.
abstract: Live attenuated nonpathogenic Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These characteristics make it very attractive as a human immunodeficiency virus (HIV) vaccine vector candidate. Here, we assessed the immunogenicity of recombinant BCG (rBCG) constructs with different simian immunodeficiency virus (SIV)gag expression cassettes as priming agents followed by a recombinant replication-incompetent New York vaccinia virus (NYVAC) boost in rhesus macaques. Unmutated rBCG constructs were used in comparison to mutants with gene deletions identified in an in vitro screen for augmented immunogenicity. We demonstrated that BCG-SIVgag is able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses. While enhanced immunogenicity was sustained at moderate levels for >1 year following the heterologous boost vaccination, we were unable to demonstrate a protective effect after repeated rectal mucosal challenges with pathogenic SIVmac251. Our findings highlight the potential for rBCG vaccines to stimulate effective cross-priming and enhanced major histocompatibility complex class I presentation, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV.
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Jaimie D
authors: JD
authors: Sixsmith
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Michael W
authors: MW
authors: Panas
authors: Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
authors: Sunhee
authors: S
authors: Lee
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Geoffrey O
authors: GO
authors: Gillard
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: KeriAnn
authors: K
authors: White
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Michelle A
authors: MA
authors: Lifton
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Harikrishnan
authors: H
authors: Balachandran
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Linh
authors: L
authors: Mach
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: John P
authors: JP
authors: Miller
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Christy
authors: C
authors: Lavine
authors: Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
authors: C Todd
authors: CT
authors: DeMarco
authors: Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
authors: Georgia D
authors: GD
authors: Tomaras
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Connie
authors: C
authors: Gee
authors: Howard Hughes Medical Institute, Department of Microbiology & Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA.
authors: Steven A
authors: SA
authors: Porcelli
authors: Howard Hughes Medical Institute, Department of Microbiology & Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA.
authors: Michelle H
authors: MH
authors: Larsen
authors: Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
authors: Richard
authors: R
authors: Frothingham
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Joern E
authors: JE
authors: Schmitz
authors: Howard Hughes Medical Institute, Department of Microbiology & Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA.
authors: William R
authors: WR
authors: Jacobs
authors: Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
authors: Barton F
authors: BF
authors: Haynes
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Norman L
authors: NL
authors: Letvin
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA bkorioth@bidmc.harvard.edu.
authors: Birgit
authors: B
authors: Korioth-Schmitz
mesh_terms: D000818:Animals; D004337:Drug Carriers; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D007111:Immunity, Cellular; D008253:Macaca mulatta; D009163:Mycobacterium bovis / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D004337:Drug Carriers; D015683:Gene Products, gag; D011994:Recombinant Proteins; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic