Protection against lethal Sendal virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with an onbound peptide

Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/1991; 88(6):2283-7. DOI: 10.1073/pnas.88.6.2283
Source: PubMed


The only peptide of Sendai virus that is recognized by cytotoxic T lymphocytes (CTL) in B6 mice was found with (i) the use of recombinant vaccinia virus constructs containing separate genes of Sendai virus and (ii) a set of overlapping peptides completely spanning the identified nucleoprotein (NP) gene product. This immunodominant NP peptide is recognized by Sendai virus-specific CTL that are known to have therapeutic effects in vivo. By subcutaneous immunization, this peptide induced Sendai virus and NP peptide-specific CTL memory responses in vivo. Most importantly, mice that had been immunized with this peptide were protected against a lethal virus dose, indicating that viral peptides can be used as antiviral T-cell vaccines. The induction of T-cell memory by free peptide immunization potentially has wide applicability in biology and medicine, including protection against infectious disease.

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Available from: Wijbe Martin Kast,
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    • "This vaccine contained a 15-mer peptide, derived from the NP protein of LCMV, suspended in incomplete Freund’s adjuvant (IFA) (31). Further experiments showed that these peptide vaccines were able to render a certain amount of protection against challenge with virus (32, 33). These results were promising, but in later studies where mice were vaccinated with 15-mer CTL epitopes derived from adenovirus type 5 early region (Ad5E1) oncogenes in combination with IFA, an enhanced outgrowth of tumors was observed following vaccination (34). "
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    • "We engineered the agfA gene of S. Typhimurium LT2 by replacing a 27 bp segment with a DNA segment encoding a T-cell epitope, i.e. Sendai virus nucleoprotein 324–332 (also called SV9) (Kast et al., 1991; Sandberg et al., 1998; Schumacher et al., 1991). Oral immunization of C57BL/6 mice with the engineered bacterial strains induced an epitope-specific T-cell response. "
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    • "Live cell counts were determined by trypan blue exclusion. Isolated cells were incubated with Fc-block for 15 minutes on ice, and then stained with PE-or APC-labeled tetramers specific for the Sendai virus nucleoprotein epitope (Sen-NP 324-332 /K b ) (Kast et al., 1991) or influenza nucleoprotein epitope (Flu-NP 366-374 /D b ) (Townsend et al., 1986) for 1 h at room temperature. All MHC class I-peptide tetramers were generated by the Trudeau Institute Molecular Biology Core. "
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