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J. Virol., 10 1997, 7881-7888, Vol 71, No. 10
DE Hassett, J Zhang and JL Whitton
Conventional vaccines are remarkably effective in adults but are much less
successful in the very young, who are less able to initiate a mature immune
response and who may carry maternal antibodies which inactivate standard
vaccines. We set out to determine whether DNA immunization might circumvent
these problems. We have previously shown that intramuscular injection of
plasmid DNA encoding the nucleoprotein (NP) gene of lymphocytic
choriomeningitis virus (LCMV) is capable of inducing immune responses and
protecting 50% of adult mice against lethal and sublethal challenge with
LCMV. Here we demonstrate that mouse pups injected with the same plasmid
hours or days after birth produce major histocompatibility
complex-restricted, NP-specific cytotoxic T lymphocytes (CTL) that persist
into adulthood; 48% of vaccinated pups responded to subsequent sublethal
viral challenge by the accelerated production of anti-NP LCMV-specific CTL,
indicating that these animals had been successfully immunized by the
plasmid DNA. In addition, these mice showed a >95% reduction in splenic
viral titers 4 days postinfection compared to control mice, demonstrating a
more rapid control of infection in vivo. Furthermore, pups born of and
suckled on LCMV-immune dams (and therefore containing passively acquired
anti-LCMV antibodies at the time of DNA inoculation) responded to the DNA
vaccine in a similar manner, showing that maternally derived anti-LCMV
antibodies do not significantly inhibit the generation of protective immune
responses following DNA vaccination. These findings suggest that, at least
in this model system, DNA immunization circumvents many of the problems
associated with neonatal immunization.
Copyright © 1997, American Society for Microbiology
Neonatal DNA immunization with a plasmid encoding an internal viral protein is effective in the presence of maternal antibodies and protects against subsequent viral challenge
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
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