title: Development of novel replication-defective lymphocytic choriomeningitis virus vectors expressing SIV antigens.
abstract: An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and homologous prime-boost regimens with rLCMV vectors induce boostable and protective T cell responses to model antigens in mice. However, cellular and humoral immune responses following homologous rLCMV vaccine regimens have not been rigorously evaluated in non-human primates (NHPs). To test whether rLCMV vectors constitute an effective vaccine platform in NHPs, we developed rLCMV vectors expressing SIVmac239 Env and Gag antigens and assessed their immunogenicity in mice and cynomolgus macaques. Immunization with rLCMV vaccine vectors expressing SIV Env and Gag was effective at generating SIV-specific T cell and antibody responses in both mice and NHPs. Epitope mapping using SIV Env in C57BL/6 mice demonstrated that rLCMV vectors induced sustained poly-functional responses to both dominant and subdominant epitopes. Our results suggest the potential of rLCMV vectors as vaccine candidates. Future SIV challenge experiments in rhesus macaques will be needed to assess immune protection by these vaccine vectors.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Penaloza MacMaster
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Shields
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Quazim A
authors.initials: QA
authors.lastname: Alayo
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Cabral
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Jimenez
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jade
authors.initials: J
authors.lastname: Mondesir
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Abishek
authors.initials: A
authors.lastname: Chandrashekar
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Cabral
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lim
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: M Justin
authors.initials: MJ
authors.lastname: Iampietro
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Provine
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Bricault
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Seaman
authors.affiliation: Hookipa Biotech AG Helmut-Qualtinger-Gasse 2, 1030 Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Orlinger
authors.affiliation: Hookipa Biotech AG Helmut-Qualtinger-Gasse 2, 1030 Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Aspoeck
authors.affiliation: Hookipa Biotech AG Helmut-Qualtinger-Gasse 2, 1030 Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fuhrmann
authors.affiliation: Hookipa Biotech AG Helmut-Qualtinger-Gasse 2, 1030 Vienna, Austria.
authors.forename: Anders E
authors.initials: AE
authors.lastname: Lilja
authors.affiliation: Hookipa Biotech AG Helmut-Qualtinger-Gasse 2, 1030 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Monath
authors.affiliation: Department of Biomedicine - Haus Petersplatz, Division of Experimental Virology, University of Basel, 4009 Basel, Switzerland.
authors.forename: Bastien
authors.initials: B
authors.lastname: Mangeat
authors.affiliation: Department of Biomedicine - Haus Petersplatz, Division of Experimental Virology, University of Basel, 4009 Basel, Switzerland.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Pinschewer
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Boston, MA 02114, USA. Electronic address: dbarouch@bidmc.harvard.edu.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D004337:Drug Carriers; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics*; D008252:Macaca fascicularis; D008810:Mice, Inbred C57BL; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D004337:Drug Carriers; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
keywords: LCMV; NHP; SIV