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RAPID COMMUNICATION
Development of a Candidate HLA A*0201 Restricted Peptide-Based Vaccine Against Human Cytomegalovirus Infection
Don J. Diamond,
Joanne York,
Ji-Yao Sun,
Christine L. Wright, and
Stephen J. Forman
From the Department of Hematology and Bone Marrow Transplantation, City of Hope Medical Center, Duarte, CA.
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. Toward this end we have studied the cellular immune response against the immunodominant matrix protein pp65 of HCMV. Using an HLA A*0201-restricted T-cell clone reactive against pp65 from peripheral blood from a seropositive 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 A*0201 motif in that region, one nonamer sensitized an autologous Epstein-Barr virus immortalized lymphocyte cell line for lysis. In vitro immunization of PBMC from HLA A*0201 and HCMV seropositive volunteers using the defined nonamer peptide stimulated significant recognition of HCMV infected or peptide-sensitized fibroblasts. Similarly, HLA A*0201 transgenic mice immunized with the nonamer peptide developed CTL that recognize both the immunizing peptide and endogenously processed pp65 in an HLA A*0201 restricted manner. Lipid modification of the amino terminus of the nonamer peptide resulted in its ability to stimulate immune respones without the use of adjuvant. This demonstration of a vaccine function of the nonamer peptide without adjuvant suggests its potential for use in an immunization trial of BMT donors to induce protective CTLs in patients undergoing allogeneic BMT.
Blood, Vol. 90 No. 5 (September 1), 1997:
pp. 1751-1767
© 1997 by The American Society of Hematology.
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Simultaneous Ex Vivo Expansion of Cytomegalovirus and Epstein-Barr Virus-Specific Cytotoxic T Lymphocytes Using B-Lymphoblastoid Cell Lines Expressing Cytomegalovirus pp65
Blood,
November 1, 1999;
94(9):
3242 - 3250.
[Abstract]
[Full Text]
[PDF]
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F. Kern, I. P. Surel, N. Faulhaber, C. Frommel, J. Schneider-Mergener, C. Schonemann, P. Reinke, and H.-D. Volk
Target Structures of the CD8+-T-Cell Response to Human Cytomegalovirus: the 72-Kilodalton Major Immediate-Early Protein Revisited
J. Virol.,
October 1, 1999;
73(10):
8179 - 8184.
[Abstract]
[Full Text]
[PDF]
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Y. Men, I. Miconnet, D. Valmori, D. Rimoldi, J.-C. Cerottini, and P. Romero
Assessment of Immunogenicity of Human Melan-A Peptide Analogues in HLA-A*0201/Kb Transgenic Mice
J. Immunol.,
March 15, 1999;
162(6):
3566 - 3573.
[Abstract]
[Full Text]
[PDF]
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