SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine.
The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans.
Cafaro
A
A
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Caputo
A
A
Maggiorella
M T
MT
Baroncelli
S
S
Fracasso
C
C
Pace
M
M
Borsetti
A
A
Sernicola
L
L
Negri
D R
DR
Ten Haaft
P
P
Betti
M
M
Michelini
Z
Z
Macchia
I
I
Fanales-Belasio
E
E
Belli
R
R
Corrias
F
F
Buttò
S
S
Verani
P
P
Titti
F
F
Ensoli
B
B
D016915:AIDS Vaccines / Q000494:pharmacology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D002678:Chimera; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D015696:Gene Products, tat / Q000276:immunology*; D006678:HIV / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008252:Macaca fascicularis; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015696:Gene Products, tat; C421254:human immunodeficiency virus type 1 Tat vaccine; D054322:tat Gene Products, Human Immunodeficiency Virus