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

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.

journal_name

Vaccine

journal_title

Vaccine

authors

Oseroff C,Sette A,Wentworth P,Celis E,Maewal A,Dahlberg C,Fikes J,Kubo RT,Chesnut RW,Grey HM,Alexander J

doi

10.1016/s0264-410x(97)00264-8

subject

Has Abstract

pub_date

1998-05-01 00:00:00

pages

823-33

issue

8

eissn

0264-410X

issn

1873-2518

pii

S0264410X97002648

journal_volume

16

pub_type

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