315 Recognition of HIV-1 CD8+ T-epitopes in Early Vertical HIV-1 Infection Z. Scott*, K. Luzuriaga Univ of Massachusetts Med Sch, Worcester
Background: Antiretroviral therapy regimens can markedly reduce mother-to-child HIV-1 transmission (MTCT) during the intrapartum period, but do not appear to reduce MTCT through breast milk. A neonatal HIV-1 vaccine could prevent breast milk transmission and provide the basis for lifetime immunity. The characterization of HIV-1 specific CD8+ T-cell responses could help in the development of a neonatal vaccine.
Methods: Autologous B-lymphoblastoid cell lines infected with recombinant vaccinia virus constructs expressing HIV-1 gag, pol, env, nef, tat, rev, vif, and vpr (representing 97% of the genome) were used as antigen-presenting cells in IFN-gamma ELISPOT assays to detect HIV-specific CD8+ T-cell responses in infants < 6 mo of age. Longitudinal analyses have been completed on 2 infants who maintained HIV-specific CD8+ T-cell responses. Overlapping HIV-1 peptide pools were used to map optimal CD8+ T-cell epitopes.
Results: HIV-specific CD8+ T-cell responses were characterized in 9 infants with detectable responses. HIV-specific CD8+ T-cell responses were directed against a single gene product (2 env, 1 nef, 1 rev) in 4 infants, whereas responses to 2 or more gene products were detected in the remaining five infants (median of 2 gene products). The hierarchy of responses was nef (5) > gag, env (4) > pol, tat, rev, vpr (2) > vif (1). Responses against HIV-1 accessory gene products represented 57% of all responses detected (12/21). Peptide mapping experiments demonstrated that distinct (tat, rev) epitopes were targeted by a set of fraternal twins despite 3 shared HLA alleles and virtually identical viral sequences. In 2 other infants, shifts in the pattern of gag epitope recognition were detected over the first year of life. For example, early gag-specific CD8+ T-cell responses in one infant were focused on the A*02-restricted VV9 epitope, but were not maintained. Strong and narrowly-focused responses to the A*02-restricted SL9 epitope were detected later during infection.
Conclusions: These data demonstrate that some young HIV-1 infected infants can generate virus-specific CD8+ T-cell responses. Accessory gene proteins were common targets of these responses. These data suggest the feasibility of a neonatal HIV-1 vaccine. Further studies evaluating the differential recognition of epitopes over the course of infection are in progress.