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Induction of protective immunity against pathogenic simian immunodeficiency virus by a foreign receptor-dependent replication of an engineered avirulent virus
Ist Teil von
Vaccine, 2000-08, Vol.18 (28), p.3310-3318
Ort / Verlag
Oxford: Elsevier Ltd
Erscheinungsjahr
2000
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
In AIDS vaccine strategies, live attenuated vaccines can confer good resistance against pathogenic virus infections but have the potential risk of inducing disease, whereas safer replication-negative strategies such as DNA vaccinations have so far failed to prevent the disease onset. Here, we developed a novel DNA vaccine strategy to induce restricted replication of an avirulent virus and evaluated it in a simian immunodeficiency virus (SIV) infection model. We generated a chimeric SIV, FMSIV, by replacing SIV
env with ecotropic Friend murine leukemia virus (FMLV)
env to confine its replication to FMLV receptor (mCAT1)-expressing cells. In primate cells lacking mCAT1, FMSIV did not replicate unless mCAT1 was introduced exogenously. Vaccination to macaques with both the FMSIV DNA and the mCAT1-expression plasmid DNA induced SIV Gag-specific cellular immune responses and resistance against pathogenic SIV
mac239 challenge more efficiently than the replication-negative control vaccination with the FMSIV DNA alone. This strategy may be useful for development of safe and effective vaccines against various kinds of pathogenic viruses.