Induction of cytotoxic and helper T cell responses by modified simian immunodeficiency virus hypervariable epitope constructs.

We previously reported the broad humoral immunogenicity of peptides synthesized according to the cumulative variability of an epitope (1,16). These peptides, hypervariable epitope constructs (HECs), are designed to represent the envelope glycoproteins of several isolates of the simian immunodeficiency virus (SIV). When HEC peptides were conjugated to palmitic acid and palmitic acid ester (lipoHECs), they promoted the induction of cellular immune responses. SIV envelope lipoHEC immunization of BALB/c and ICR mice resulted in up to 80% cytotoxic T lymphocyte (CTL) lysis of SIV envelope-expressing target cells and SIV envelope-specific delayed type hypersensitivity (DTH). This DTH response was significantly higher than that of single peptide controls, and the response peaked at 24 hours. Strong SIV envelope-specific T-cell proliferative responses were also induced in mice with stimulation indexes higher than 20 for spleen cells and higher than 10 for lymph node cells. Overall, our results demonstrate that conjugation of these variable synthetic peptides to a lipid moiety results in an immunogen capable of inducing strong and cross-reactive cellular immune responses.