title: Humoral immunity induced by mucosal and/or systemic SIV-specific vaccine platforms suggests novel combinatorial approaches for enhancing responses.
abstract: Combinatorial HIV/SIV vaccine approaches targeting multiple arms of the immune system might improve protective efficacy. We compared SIV-specific humoral immunity induced in rhesus macaques by five vaccine regimens. Systemic regimens included ALVAC-SIVenv priming and Env boosting (ALVAC/Env); DNA immunization; and DNA plus Env co-immunization (DNA&Env). RepAd/Env combined mucosal replication-competent Ad-env priming with systemic Env boosting. A Peptide/Env regimen, given solely intrarectally, included HIV/SIV peptides followed by MVA-env and Env boosts. Serum antibodies mediating neutralizing, phagocytic and ADCC activities were induced by ALVAC/Env, RepAd/Env and DNA&Env vaccines. Memory B cells and plasma cells were maintained in the bone marrow. RepAd/Env vaccination induced early SIV-specific IgA in rectal secretions before Env boosting, although mucosal IgA and IgG responses were readily detected at necropsy in ALVAC/Env, RepAd/Env, DNA&Env and DNA vaccinated animals. Our results suggest that combined RepAd priming with ALVAC/Env or DNA&Env regimen boosting might induce potent, functional, long-lasting systemic and mucosal SIV-specific antibodies.
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Vargas-Inchaustegui
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Iskra
authors.initials: I
authors.lastname: Tuero
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Venkatramanan
authors.initials: V
authors.lastname: Mohanram
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Musich
authors.affiliation: Animal Models and Retroviral Vaccine Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Poonam
authors.initials: P
authors.lastname: Pegu
authors.affiliation: Human Retrovirus Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Human Retrovirus Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Bear
authors.affiliation: Biostatistics and Data Management Section, CCR, NCI, NIH, Rockville, MD 20850, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Venzon
authors.affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: Guy R
authors.initials: GR
authors.lastname: Pilkington
authors.affiliation: Animal Models and Retroviral Vaccine Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Namal P M
authors.initials: NP
authors.lastname: Liyanage
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.affiliation: Animal Models and Retroviral Vaccine Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Shari N
authors.initials: SN
authors.lastname: Gordon
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Hogg
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Blake
authors.initials: B
authors.lastname: Frey
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: L Jean
authors.initials: LJ
authors.lastname: Patterson
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Janet
authors.initials: J
authors.lastname: DiPasquale
authors.affiliation: Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Inovio Pharmaceuticals, Inc., Blue Bell, PA 19422, United States.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Infectious Diseases Research Institute, Seattle, WA 98102, United States.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.affiliation: Animal Models and Retroviral Vaccine Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States.
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
authors.affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.affiliation: Human Retrovirus Section, Vaccine Branch, CCR, NCI, NIH, Frederick, MD 21702, United States.
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.affiliation: Immune Biology of Retroviral Infection Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, United States. Electronic address: guroffm@mail.nih.gov.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D004359:Drug Therapy, Combination; D058501:Enzyme-Linked Immunospot Assay; D015686:Gene Products, env / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D013997:Time Factors; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; D000914:Antibodies, Viral; D015686:Gene Products, env; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit
keywords: Functional antibody activities; Memory B cells; Mucosal and systemic humoral immunity; Poxvirus-, adenovirus-, and DNA-based vaccines; Simian Immunodeficiency Virus