Pools of lipidated HTL-CTL constructs prime for multiple HBV and HCV CTL epitope responses

Carla Oseroff, Alessandro Sette, Peggy Wentworth, Esteban Celis, Ajesh Maewal, Carol Dahlberg, John Fikes, Ralph T. Kubo, Robert W. Chesnut, Howard M. Grey, Jeff Alexander

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Various peptide-based approaches to simultaneous induction of multiple cytotoxic T lymphocyte (CTL) responses were evaluated as part of ongoing efforts to develop immunotherapeutic vaccines for use in humans. To this end, HLA (human histocompatibility leukocyte antigen)-A2-restricted epitopes from several specific viral proteins were tested in an HLA-A2 transgenic mouse model system, which mimics human CTL responses to these viral proteins. Multiple CTL responses were elicited by immunization with either peptides emulsified in incomplete Freund's adjuvant (IFA), or lipidated peptides administered in phosphate buffered saline (PBS). In the case of lipidated peptides, induction of CTL responses was crucially dependent on the presence of helper T lymphocyte (HTL) epitopes, and most efficient in the case of lipidated covalently linked HTL-CTL epitope constructs. CTL could also be induced by immunization with lipidated HTL epitopes simply mixed with CTL epitopes and formulated in PBS. However, this approach was highly dependent on the particular lipidated HTL/CTL combination utilized, and was marginally effective for simultaneous priming of multiple CTL responses. By contrast, all HTL/CTL combinations were potent immunogens when delivered as lipidated, covalently linked molecules. This was the most effective of the approaches analysed in terms of multi-epitope priming, as demonstrated by the induction of simultaneous CTL responses to a pool of five different epitopes.

Original languageEnglish (US)
Pages (from-to)823-833
Number of pages11
JournalVaccine
Volume16
Issue number8
DOIs
StatePublished - May 1 1998
Externally publishedYes

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Keywords

  • CTL response
  • Lipidated peptides
  • Multiple epitopes

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Oseroff, C., Sette, A., Wentworth, P., Celis, E., Maewal, A., Dahlberg, C., Fikes, J., Kubo, R. T., Chesnut, R. W., Grey, H. M., & Alexander, J. (1998). Pools of lipidated HTL-CTL constructs prime for multiple HBV and HCV CTL epitope responses. Vaccine, 16(8), 823-833. https://doi.org/10.1016/S0264-410X(97)00264-8