DEVELOPMENT OF A CANDIDATE HLA A-ASTERISK-0201 RESTRICTED PEPTIDE-BASED VACCINE AGAINST HUMAN CYTOMEGALOVIRUS-INFECTION

The development of a protective cellular immune response against human cytomegalovirus (HCMV) is the most important determinant of recovery from HCMV infection after allogeneic bone marrow transplantation (BMT) . The ultimate aim of our study is to develop an antigen-specific and peptide-based vaccine strategy against HCMV in the setting of BMT. Tow ard this end we have studied the cellular immune response against the immunodominant matrix protein pp65 of HCMV, Using an HLA A0201-restri cted T-cell clone reactive against pp65 from peripheral blood from a s eropositive individual, we have mapped the position of the cytolytic T lymphocyte (CTL) epitope from HCMV pp65 to an 84-amino acid segment. Of the four peptides which best fit the HLA A0201 motif in that regio n, one nonamer sensitized an autologous Epstein-Barr virus immortalize d lymphocyte cell line for lysis, In vitro immunization of PBMC from H LA A0201 and HCMV seropositive volunteers using the defined nonamer p eptide stimulated significant recognition of HCMV infected or peptide- sensitized fibroblasts. Similarly, HLA A0201 transgenic mice immunize d with the nonamer peptide developed CTL that recognize both the immun izing peptide and endogenously processed pp65 in an HLA A0201 restric ted manner, Lipid modification of the amino terminus of the nonamer pe ptide resulted in its ability to stimulate immune respones without the use of adjuvant, This demonstration of a vaccine function of the nona mer peptide without adjuvant suggests its potential for use in an immu nization trial of BMT donors to induce protective CTLs in patients und ergoing allogeneic BMT. (C) 1997 by The American Society of Hematology .