Replicons from positive strand RNA viruses for naked RNA immunization against influenza

Background: Genetic immunization is a powerful tool for vaccine development, but faces the potential drawback of persistence of the injected DNA sequences in the host. Methods: Replicons derived from poliovirus (PV), attenuated Mengo virus (MV) and Semliki Forest virus (SFV) genomes for which the in...

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Bibliographic Details
Published inInternational Congress series Vol. 1219; pp. 923 - 929
Main Authors Vignuzzi, Marco, Gerbaud, Sylvie, van der Werf, Sylvie, Escriou, Nicolas
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.10.2001
Subjects
Cytotoxic T lymphocytes
Hemagglutinin
Humoral response
Nucleoprotein
Picornavirus
Recombinant
Semliki Forest virus
Vaccine vector
Picornavirus
Humoral response
Vaccine vector
Semliki Forest virus
Hemagglutinin
Nucleoprotein
Cytotoxic T lymphocytes
Recombinant
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Summary:Background: Genetic immunization is a powerful tool for vaccine development, but faces the potential drawback of persistence of the injected DNA sequences in the host. Methods: Replicons derived from poliovirus (PV), attenuated Mengo virus (MV) and Semliki Forest virus (SFV) genomes for which the influenza nucleoprotein (NP) or hemagglutinin (HA) sequences replace structural protein sequences were constructed. Their immunogenicity was evaluated in C57BL/6 mice following intramuscular injection in the form of naked RNA. Results: Replicons derived from the SFV, PV or MV genomes were shown to replicate upon transfection of cells and permit NP expression. Expression of the HA in a correctly glycosylated form could be achieved from the SFV-derived genome or from a dicistronic PV-derived genome for which synthesis of the heterologous antigen was uncoupled from that of the truncated poliovirus polyprotein that was placed under the control of the EMCV-IRES. Injection of the NP expressing replicons in the form of naked RNA into mice resulted in the induction of an anti-NP cytotoxic and/or humoral immune response. For the SFV-derived replicon, the response was found to be protective to a level comparable to that achieved by DNA immunization. Conclusions: Recombinant replicons derived from positive strand RNA virus genomes could provide a useful alternative to DNA vaccines.
ISSN:0531-5131
1873-6157
DOI:10.1016/S0531-5131(01)00409-5