Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with free synthetic peptide

Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 04/1991; 88(6):2283-7. DOI: 10.1073/pnas.88.6.2283
Source: PubMed

ABSTRACT 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, Aug 20, 2015
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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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    • "Note that the probability that a virus would simultaneously mutate multiple epitopes decreases exponentially with the number of epitopes. Practically all previous attempts (Dietrich et al., 2005; Kast et al., 1991; Wang et al., 2005) to develop vaccines were focused on a single or a limited number of epitopes. For example, using super-type epitopes or promiscuous epitopes (De Groot and Rappuoli, 2004) or focusing on a limited number of alleles (Gulukota, 2003; Gulukota and DeLisi, 1996; Wang et al., 2005). "
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