Induction of cytotoxic T lymphocytes (CTL) specific for HIV-1 or protection against tumor challenge by intranasal immunization with CTL peptide and cholera toxin

To evaluate mucosal routes of immunization for the induction of HIV-1 specific CTL, BALB/c mice were intranasally (IN) immunized with octameric peptides corresponding to a defined CTL epitope in HIV-1 gp120 (R10I) and the mucosal adjuvant cholera toxin (CT). IN immunization with 50 ug R10I peptide and 1 ug CT induced CTL responses in both cervical lymph node (CLN) and spleen (SP) cells after 4 days in vitro restimulation. CLN effector cells produced 18.8%, 13%, and 4.5% specific lysis of R10I-pulsed target cells at effector:Target (E:T) ratios of 100:1, 50:1, and 25:1, respectively. SP effector cells produced 44.3%, 19%, and 7.6% specific lysis of R10I-pulsed target cells at an E:T ratio of 100:1, 50:1, and 25:1, respectively. Similar results were obtained by IN immunization of C57BL/6 mice with a defined CTL epitope from ovalbumin (OVA-8) and CT. Others have reported that OVA specific CTL responses were able to protect mice against tumor development after injection with E.G7-OVA tumor cells that express chicken ovalbumin. IN immunization with OVA and CT protected against tumor development after subcutaneous challenge with E.G7-OVA cells suggesting that the OVA-8 specific CTLs were functioning in vivo. IN immunization was as effective as peptide-pulsed dendritic cells for the induction of protective CTL responses. IN immunization with CT and peptides corresponding to known CTL epitopes from HIV or tumor antigens may provide a means to induce specific CTL responses in vivo.