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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Published in | International Congress series Vol. 1219; pp. 923 - 929 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier B.V
01.10.2001
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Subjects | |
Online Access | Get full text |
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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. |
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ISSN: | 0531-5131 1873-6157 |
DOI: | 10.1016/S0531-5131(01)00409-5 |