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Departments of
*
Pediatrics and
Pathology and the
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461; and
§
Institut National de la Santé et de la Recherche Médicale U404, Immunity and Vaccination, Institut Pasteur de Lyon, Lyon, France
An intranasal vaccine vector would elicit protective immunity at
the respiratory mucosa, the portal of entry and the primary site for
replication for measles virus (MV) and other respiratory viruses. In a
murine model of pulmonary Shigella, we demonstrate here
that a candidate-attenuated Shigella vaccine vector is
safely tolerated in IFN-
deficient mice at an inoculum that is 1
million-fold higher than the inoculum of the wild-type parent strain
that would be lethal for greater than 90% of these mice. Also,
following intranasal inoculation, the 
asd Shigella
harboring a DNA MV vaccine plasmid induces a vigorous
MV-specific Th1-type (both CD8+ CTL and IFN-) and, to a
lesser degree, Th2-type responses among splenocytes in addition to low
levels of IgG and IgA in the serum. Priming for MV-specific CTL
responses was possible in mice that had prior infection with a
wild-type Shigella of the same serotype. Remarkably, mice
immunized by the intranasal route with attenuated Shigella
harboring the DNA MV vaccine plasmid had a level of
MV-specific CTL activity among splenocytes that was comparable with
levels observed in mice immunized by the i.p. route with attenuated
Salmonella typhi harboring the same DNA vaccine plasmid,
despite the fact that Shigella remained localized to the
lungs, yet Salmonella disseminated to the spleen following
inoculation. Thus, asd Shigella represents a very useful
vector for delivery of DNA vaccines to mucosal lymphoid
tissues.
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