A. Cafaro et al., SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine, J MED PRIM, 29(3-4), 2000, pp. 193-208
The Tat protein of human immunodeficiency virus (HIV) is produced very earl
y after infection, plays a key role in the virus life cycle and in acquired
immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well con
served among all virus clades. Notably, a Tat-specific immune response corr
elates 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 immun
odeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disea
se onset in cynomolgus monkeys. No signs of virus replication were found in
five out of seven vaccinated macaques for almost 1 year of followup. Since
the inoculated virus (derived from rhesus dr 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 c
hallenge. Finally, the studies of the Tat-specific: immunological responses
indicate a correlation of protection with a. cytotoxic T cell response. Th
us, a Tat-based vaccine is a promising candidate for preventive and therape
utic vaccination in humans.