1) Rabies DNA vaccines encoding the glycoprotein (G) protect mice and nonhuman primates against rabies virus. 2) The immunostimulant monophosphoryl lipid A (MPL) enhances primary neutralizing antibody responses elicited by DNA vaccines; MPL suppresses anamnestic neutralizing antibody responses elicited by DNA vaccines. 3) Recombinant poxvirus rabies vaccines elicit high titers of neutralizing antibody in DNA or inactivated viral protein vaccinated mice; booster immunizations with a recombinant poxvirus vaccine do not enhance antibody titers of mice previously vaccinated with a similar vaccine. Booster immunizations with inactivated viral protein or DNA vaccines enhance antibody titers of mice previously vaccinated with recombinant poxvirus, DNA or inactivated viral protein. 4) Recombinant poxvirus rabies vaccines expressing only G or G and nucleoprotein are equally efficacious in protecting mice two years after vaccination. 5) Intradermal DNA vaccination in the mouse ear pinna elicits rapid and elevated neutralizing antibody responses. 6) Nonhuman primates vaccinated once with DNA via gene gun maintain protective levels of neutralizing antibody for at least 9 months after vaccination. 7) Neutralizing antibody responses are quickly elevated to protective levels after booster vaccinations with DNA. - Rabies, vaccines, DNA, recombinant poxvirus, antibody, monkeys, immunostimulant, prophylaxis, therapy - Human Subjects

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000072-28
Application #
6288790
Study Section
Special Emphasis Panel (LPVD)
Project Start
Project End
Budget Start
Budget End
Support Year
28
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Lodmell, Donald L; Esposito, Joseph J; Ewalt, Larry C (2004) Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised Vaccine 22:3329-33
Lodmell, Donald L; Ewalt, Larry C (2004) Rabies cell culture vaccines reconstituted and stored at 4 degrees C for 1 year prior to use protect mice against rabies virus. Vaccine 22:3237-9
Lodmell, Donald L; Parnell, Michael J; Weyhrich, John T et al. (2003) Canine rabies DNA vaccination: a single-dose intradermal injection into ear pinnae elicits elevated and persistent levels of neutralizing antibody. Vaccine 21:3998-4002
Lodmell, Donald L; Parnell, Michael J; Bailey, John R et al. (2002) Rabies DNA vaccination of non-human primates: post-exposure studies using gene gun methodology that accelerates induction of neutralizing antibody and enhances neutralizing antibody titers. Vaccine 20:2221-8
Arai, Y T; Takahashi, H; Kameoka, Y et al. (2001) Characterization of Sri Lanka rabies virus isolates using nucleotide sequence analysis of nucleoprotein gene. Acta Virol 45:327-33
Lodmell, D L; Ewalt, L C (2001) Post-exposure DNA vaccination protects mice against rabies virus. Vaccine 19:2468-73
Lodmell, D L; Ray, N B; Ulrich, J T et al. (2000) DNA vaccination of mice against rabies virus: effects of the route of vaccination and the adjuvant monophosphoryl lipid A (MPL). Vaccine 18:1059-66
Lodmell, D L; Ewalt, L C (2000) Rabies vaccination: comparison of neutralizing antibody responses after priming and boosting with different combinations of DNA, inactivated virus, or recombinant vaccinia virus vaccines. Vaccine 18:2394-8