title: Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity.
abstract: Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response. We comparatively assessed several vaccine vector delivery systems-three formulations of a plasmid DNA vector, the modified vaccinia Ankara (MVA) virus, and a replication incompetent adenovirus type 5 (Ad5) vector-expressing the SIV gag protein for their ability to elicit such immune responses in monkeys. The vaccines were tested either as a single modality or in combined modality regimens. Here we show that the most effective responses were elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector. After challenge with a pathogenic HIV-SIV hybrid virus (SHIV), the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the virus infection. The replication-defective adenovirus is a promising vaccine vector for development of an HIV-1 vaccine.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Tong-Ming
authors.initials: TM
authors.lastname: Fu
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Davies
authors.forename: Robert K
authors.initials: RK
authors.lastname: Evans
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Simon
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Trigona
authors.forename: Sheri A
authors.initials: SA
authors.lastname: Dubey
authors.forename: Lingyi
authors.initials: L
authors.lastname: Huang
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Harris
authors.forename: Romnie S
authors.initials: RS
authors.lastname: Long
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: Larry
authors.initials: L
authors.lastname: Handt
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Freed
authors.forename: Natasha V
authors.initials: NV
authors.lastname: Persaud
authors.forename: Liming
authors.initials: L
authors.lastname: Guan
authors.forename: Kara S
authors.initials: KS
authors.lastname: Punt
authors.forename: Aimin
authors.initials: A
authors.lastname: Tang
authors.forename: Minchun
authors.initials: M
authors.lastname: Chen
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wilson
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Collins
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: Heidecker
authors.forename: V Rose
authors.initials: VR
authors.lastname: Fernandez
authors.forename: Helen C
authors.initials: HC
authors.lastname: Perry
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Joyce
authors.forename: Karen M
authors.initials: KM
authors.lastname: Grimm
authors.forename: James C
authors.initials: JC
authors.lastname: Cook
authors.forename: Paul M
authors.initials: PM
authors.lastname: Keller
authors.forename: Denise S
authors.initials: DS
authors.lastname: Kresock
authors.forename: Henryk
authors.initials: H
authors.lastname: Mach
authors.forename: Robert D
authors.initials: RD
authors.lastname: Troutman
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Isopi
authors.forename: Donna M
authors.initials: DM
authors.lastname: Williams
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Bohannon
authors.forename: David B
authors.initials: DB
authors.lastname: Volkin
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Ayako
authors.initials: A
authors.lastname: Miura
authors.forename: Georgia R
authors.initials: GR
authors.lastname: Krivulka
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lifton
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: Jörn E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caulfield
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bett
authors.forename: Rima
authors.initials: R
authors.lastname: Youil
authors.forename: David C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000276:immunology* / Q000502:physiology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015683:Gene Products, gag; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic