CROSS-CLADE ENVELOPE GLYCOPROTEIN-160 SPECIFIC CD8(-LYMPHOCYTE RESPONSES IN EARLY HIV TYPE-1 CLADE-B INFECTION() CYTOTOXIC T)

A major objective of current HIV-1 vaccination strategies is the induc tion of HIV-l-specific CD8(+) MHC class I-restricted CTL responses, wh ich are suggested to play a pivotal role in viral clearance and protec tion against HIV-1 disease progression. However, the marked genetic di versity of HIV-1 and existence of distinct viral subtypes or clades co uld potentially hinder the development of a universally efficacious HI V-1 vaccine, In this study we examined HIV-1 intraclade (B-LAI versus B-MN) Env gp160-specific CTL reactivity in recently HIV-1 clade B-infe cted individuals. We further evaluated the extent of interclade CTL cr oss-recognition of the divergent A and C Env gp160 subtypes, that are highly prevalent in the global pandemic, Freshly isolated PBMCs were s timulated in vitro with autologous PBMCs infected with recombinant vac cinia vectors expressing HIV-1 env, gag, pol, and nef genes derived fr om HIV-1 clade B, All 13 of the 19 HIV-1-seropositive subjects who eli cited significant clade B Env gp160(LAI) CD8(+) CTL responses also dem onstrated comparable levels of CTL cross-reactivity against clade C-92 BR025 Env gp160, Nine of these individuals also showed extensive inter clade CTL cross-recognition of clade A(92UG037) Env gp160, Two HLA cla ss I B7 donors had nondetectable intraclade CTL response against B Env gp160(MN), while generating significant intraclade BLAI and interclad e (A and C) Env gp160 CTL cross-reactivity, These observations serve t o underscore the central importance of the HLA background of individua ls in determining the pattern of immune reactivity to natural HIV-1 in fection and presumably vaccines. Five donors studied also demonstrated broad CTL cross-reactivity against clade A(92UG037) Gag p55, Pol, and /or Nef antigens, In conclusion, this present study indicates that the re is a considerable degree of CD8+ CTL cross-recognition of the highl y divergent HIV-1 Env gp160 subtypes during early phases of HIV-1 infe ction. Such findings suggest that HIV-1 vaccines based on a single cla de that can induce extensive cross-clade immunity may demonstrate util ity in diverse geographical regions.