Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity.
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.
Shiver
John W
JW
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Fu
Tong-Ming
TM
Chen
Ling
L
Casimiro
Danilo R
DR
Davies
Mary-Ellen
ME
Evans
Robert K
RK
Zhang
Zhi-Qiang
ZQ
Simon
Adam J
AJ
Trigona
Wendy L
WL
Dubey
Sheri A
SA
Huang
Lingyi
L
Harris
Virginia A
VA
Long
Romnie S
RS
Liang
Xiaoping
X
Handt
Larry
L
Schleif
William A
WA
Zhu
Lan
L
Freed
Daniel C
DC
Persaud
Natasha V
NV
Guan
Liming
L
Punt
Kara S
KS
Tang
Aimin
A
Chen
Minchun
M
Wilson
Keith A
KA
Collins
Kelly B
KB
Heidecker
Gwendolyn J
GJ
Fernandez
V Rose
VR
Perry
Helen C
HC
Joyce
Joseph G
JG
Grimm
Karen M
KM
Cook
James C
JC
Keller
Paul M
PM
Kresock
Denise S
DS
Mach
Henryk
H
Troutman
Robert D
RD
Isopi
Lynne A
LA
Williams
Donna M
DM
Xu
Zheng
Z
Bohannon
Kathryn E
KE
Volkin
David B
DB
Montefiori
David C
DC
Miura
Ayako
A
Krivulka
Georgia R
GR
Lifton
Michelle A
MA
Kuroda
Marcelo J
MJ
Schmitz
Jörn E
JE
Letvin
Norman L
NL
Caulfield
Michael J
MJ
Bett
Andrew J
AJ
Youil
Rima
R
Kaslow
David C
DC
Emini
Emilio A
EA
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
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015683:Gene Products, gag; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic