Induction of HIV-specific cytotoxic T lymphocytes by a V3 loop peptide: a new method for rapid in vivo induction using unmodified synthetic peptides.
Int Conf AIDS 1992 Jul 19-24; 8:We52 (abstract no. WeD 1040) Sastry KJ, Nehete P, Venkatanarayanan S, Morkowski J, Platsoucas CD, Arlinghaus RB; M.D. Anderson Cancer Center, Houston, TX 77030.
Efforts to generate a vaccine against human immunodeficiency virus (HIV) infection have focused on inducing neutralizing antibodies. However, cytotoxic T-lymphocyte (CTL) responses are a major defense against viral infections and more importantly CTL epitopes can be defined by short synthetic peptides. We have developed a new protocol for rapid generation of specific CTLs in mice by a single injection of unmodified free synthetic peptides into the foot-pad (Sastry et al., Virology in Press, 1992). Using this protocol we demonstrated that a 15 amino acid peptide (aa 315-329) derived from the immunodominant V3-loop of HIV gp120 induced HIV env-specific CD8+ CTLs in mice, which lyse cells expressing gp160 in a MHC-restricted fashion. CTLs are induced in the adjacent lymph node in less than 10 days. Results by others have established that HIV-infected AIDS patients uniformly produce CTLs specific for this same epitope. Based on these results, we propose that a mixture of 5 to 6 peptides from various HIV isolates that contain this epitope could be included in an HIV vaccine in combination with other immunogenic peptides. We also successfully induced in vivo CTL activity with unmodified synthetic peptides from the nucleoproteins of influenza and sendai viruses, indicating general applicability of our method for rapid screening of CTL epitopes.
Keywords: AEGIS, T-Lymphocytes, Cytotoxic, HIV, Peptides, HIV Envelope Protein gp120, Antigens, CD8, AIDS Vaccines, HIV Antigens, HIV Core Protein p24, Nucleoproteins, HIV Antibodies, HIV Envelope Protein gp160, HIV Envelope Protein gp41, Human, Animal, Mice, ICA8
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WeD1040
