Recombinant parvovirus-like particles for inducing cytotoxic T-cell response: use in antiviral and antitumoral drugs or vaccines
Description of invention:
Cytotoxic CD8+ T lymphocytes (CTLs) play a critical role in the elimination of cells infected by pathogens and in tumor regression. Although several strategies have been recently developed to induce efficient CTL responses, each of these approaches presents certain risks and/or other limitations. Therefore, the development of a safe strategy to induce CTL responses with non-replicating antigens remains an important prerequisite for the design of efficient vaccines.
In the present invention, researchers at the Institut Pasteur, in collaboration with scientists at Ingenasa (Spain), have developed an antigen delivery system based on hybrid recombinant parvovirus like-particles. Hybrid virus-like particles (VLP) are prepared by self-assembly of the modified porcine parvovirus VP2 capsid protein carrying CD8+ T cell epitopes from virus or human tumors. Immunization of mice with these hybrid pseudoparticles carrying a viral CTL epitope, without adjuvant, induced strong CTL responses that persisted in vivo for at least 9 months and were capable to fully protect mice against a lethal viral infection.
Moreover, strong specific CTL responses are induced by VLPs carrying human HLA-A2 restricted tumor epitopes.
Importantly, these VLPs also induce strong CTL responses when administered intranasally, in the absence of any adjuvant.
These recombinant particles containing a single type of protein are easily produced by the baculovirus expression system and, therefore, represent a promising, practical and safe strategy to induce strong CTL responses for prophylactic or therapeutic vaccination against virus or tumors.
Priority application EP 96400009 filed January 2, 1996
Various patents pending
Sedlik C, Dadaglio G, Saron MF, Deriaud E, Rojas M, Casal SI and Leclerc C. J Virol 2000, 74: 5769-75
Sedlik C, Dridi A, Deriaud E, M.F. Saron, Sarraseca J, Casal I and Leclerc C. J Virol 1999, 73, 2739-2744
Sedlik C, Saron M, Sarraseca J, Casal I and Leclerc C. Proc Natl Acad Sci U S A 1997, 94: 7503-8
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