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ROLE OF HOST AND VIRAL FACTORS IN RESISTANCE TO RABIES VIRUS INFECTION IN MICE

$0Z01FY2000AINIH

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Abstract

1) Rabies DNA vaccines encoding the glycoprotein (G) protect mice and nonhuman primates against rabies virus. 2) Recombinant poxvirus rabies vaccines elicit high titers of neutralizing antibody in mice previously vaccinated with DNA or inactivated rabies virus; booster immunizations with a recombinant poxvirus vaccine do not enhance antibody titers of mice previously vaccinated with a similar vaccine. 3) Booster immunizations with inactivated virus or DNA vaccines enhance antibody titers of mice previously vaccinated with recombinant poxvirus, DNA or inactivated virus. 4) Recombinant poxvirus rabies vaccines expressing only G or G and thenucleoprotein are equally efficacious in protecting mice two years after vaccination. 5) Intradermal DNA vaccination via needle in the mouse ear pinna elicits accelerated and elevated neutralizing antibody responses. 6) Transdermal immunization of mice with a DNA vaccine elicits protection against rabies virus.7) Nonhuman primates vaccinated once with DNA via gene gun maintain protective levels of neutralizing antibody for at least 12 months after vaccination. Several monkeys vaccinated IM with DNA did not produce neutralizing antibody. One year after vaccination, the monkeys vaccinated IM or via gene gun were protected against rabies virus challenge.7) Neutralizing antibody responses are quickly elevated to protective levels in mice and monkeys after multiple DNA vaccine booster vaccinations. 8) Dogs vaccinated ID, IM or via gene gun with the DNA vaccine elicit high titers of neutralizing antibody 9)Post-exposure rabies DNA vaccination, in combination with a single dose of rabies immune serum, protects mice against rabies virus.

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