DNA immunization of newborn mice with plasmids expressing influenza virus proteins.
Item
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Title
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DNA immunization of newborn mice with plasmids expressing influenza virus proteins.
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Identifier
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AAI9820514
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identifier
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9820514
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Creator
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Bot, Adrian I.
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Contributor
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Adviser: Constantin A. Bona
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Date
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1998
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Immunology | Biology, Microbiology
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Abstract
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The effective immunization of neonates and infants is an essential goal for the human vaccination. Neonates and infants are more difficult to immunize since their immune system is not mature and they are more susceptible to tolerance induction.;We have investigated the plasmid-based immunization as a potential strategy for neonatal vaccination, using the preclinical model of the immune response in BALB/c mice to Influenza virus antigens. Newborn mice injected with three different plasmids expressing whole HA and NP antigens, or HA-derived dominant B and T cell epitopes developed significant virus-specific cross-reactive CTLI, Th and B cell immunity. The lack of tolerance induction subsequent to neonatal inoculation of plasmid-based expression vectors, may be due to the continuous exposure of the peripheral lymphocytes to low doses of foreign antigen, associated with the adjuvant effect of the bacterial DNA. The neonatal plasmid-based vaccination elicited immune responses against four type-A Influenza virus strains, of different subtypes. The immune response was protective as demonstrated by the survival rate and/or pulmonary virus clearance subsequently to the infection with three different mouse-adapted strains of Influenza virus. The protection ability of the plasmid-based newborn immunization was significantly enhanced by the co-inoculation of plasmids expressing HA and NP. The naked DNA immunization of newborn mice displayed two advantages as compared to the inactivated vaccine: first, the plasmid immunization elicited cross-reactive CTLs and secondly, it was protective, in sharp contrast to the UV-inactivated virus that induced immune unresponsiveness.;The study of the relationship between the maternal immunity and the immune responsiveness of the offsprings, suggested that the plasmid-based immunization may circumvent to a certain extent the inhibitory effect of the maternal antibodies. Futhermore, rather than inducing central tolerance, the maternal plasmid-based immunization elicited protective antibodies that were transmitted to the progeny.;Experiments addressing the mechanism of protection against Influenza virus following the naked DNA immunization, suggested the involvement of in vivo transfected APC as well as of cytokines like {dollar}\rm IFN\gamma{dollar} and IL-4.;Together, our results pinpoint to a potential application for the plasmid-based immunization of infants, against microbes responsible for infectious diseases with high morbidity and mortality in the young population.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
