Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P)

Recent evidence suggests that a CD8-mediated cytotoxic T cell response agai nst the Tat protein of human immunodeficiency virus (HIV)/simian immunodefi ciency virus (SIV) controls primary infection after pathogenic virus challe nge, and correlates with the status of long-term nonprogressor in humans. D ue to the presence of unmethylated CpG sequences. DNA vaccination can boost the innate immunity driving more potent T cell-mediated immune responses. Therefore. cynomolgus monkeys were vaccinated with a tat-expressing vector containing defined unmethylated CpG sequences (pCV-tat). Here it is shown t hat the intramuscular inoculation of the pCV-tat contained primary infectio n with the highly pathogenic SHIV89.6P virus preventing the CD4(+) T cell d ecline in all the vaccinated monkeys. Undetectable virus replication and ne gative virus isolation correlated in all cases with the presence of anti-Ta t CTLs. However, a CD8-mediated non cytolytic antiviral activity was also p resent in all protected animals. Of note, this activity was absent in the c ontrols but was present in the monkey inoculated with the CpG-rich vector a lone that was partially protected against viral challenge (i.e. no virus re plication but positive virus isolation). These results suggest that a CTL r esponse against Tat protects against primary infection by blocking virus re plication at its early stage, in the absence of sterilizing immunity. Never theless, the boost of the innate immunity by CpG sequences can contribute t o this protection both by driving more potent CTL responses and by inducing other CD8-mediated antiviral activities. Thus, the CpG-rich rat DNA vaccin e may represent a promising candidate for preventive and therapeutic vaccin ation against AIDS. (C) 2001 Elsevier Science Ltd. All rights reserved.