DNA immunization protects nonhuman primates against rabies virus.
More than 40,000 people die annually from rabies worldwide. Most of these fatalities occur in developing countries, where rabies is endemic, public health resources are inadequate and there is limited access to preventive treatment. Because of the high cost of vaccines derived from cell culture, many countries still use vaccines produced in sheep, goat or suckling mouse brain. The stability and low cost for mass production of DNA vaccines would make them ideal for use in developing countries. To investigate the potential of DNA vaccines for rabies immunization in humans, we vaccinated Macaca fascicularis (Cynomolgus) monkeys with DNA encoding the glycoprotein of the challenge virus standard rabies virus, or with a human diploid cell vaccine (HDCV). The monkeys then were challenged with a non-passaged rabies virus. DNA or HDCV vaccination elicited comparable primary and anamnestic neutralizing antibody responses. All ten vaccinated monkeys (DNA or HDCV) survived a rabies virus challenge, whereas monkeys vaccinated with only the DNA vector developed rabies. Furthermore, serum samples from DNA- or HDCV-vaccinated monkeys neutralized a global spectrum of rabies virus variants in vitro. This study shows that DNA immunization elicits protective immunity in nonhuman primates against lethal challenge with a human viral pathogen of the central nervous system. Our findings indicate that DNA vaccines may have a promising future in human rabies immunization.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. dlodmell@atlas.niaid.nih.gov
D L
DL
Lodmell
N B
NB
Ray
M J
MJ
Parnell
L C
LC
Ewalt
C A
CA
Hanlon
J H
JH
Shaddock
D S
DS
Sanderlin
C E
CE
Rupprecht
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D000917:Antibody Formation; D001921:Brain / Q000821:virology; D002685:Chiroptera; D004285:Dogs; D006041:Goats; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D009500:Neutralization Tests; D011323:Primates; D011818:Rabies / Q000276:immunology / Q000517:prevention & control*; D011819:Rabies Vaccines; D012756:Sheep; D019444:Vaccines, DNA
D000914:Antibodies, Viral; D011819:Rabies Vaccines; D019444:Vaccines, DNA