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Data regarding the occurrence of a viremia during rabies virus infections are contradictory. Here, we attempted to clarify the dissimilar results using a qualitative TaqMan PCR assay to detect viral RNA in blood of mice that had been injected intramuscularly with rabies virus. Viral RNA was detected at two different intervals. Initially, RNA was present in blood of 30/32 (94%) mice, from 1h to 2 days...
Rabid dog exposures result in >99% of human rabies deaths worldwide. Ninety-eight percent of these cases occur in developing countries. Thus, the best protection against human rabies would be prevention through adequate vaccination of the reservoir population. The difficulty in re-locating ownerless, freely roaming dogs for booster vaccinations, in addition to poor coverage with inadequate vaccines,...
Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4 + helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s)...
Human exposure to rabid dogs in developing countries is an ongoing problem that continues to demand effective, safe, and affordable post-exposure rabies vaccinations. Sheep and suckling mouse brain rabies vaccines used in developing countries are being replaced by expensive inactivated-virus cell culture vaccines. Human studies using cell culture vaccines have determined that cost is reduced and protection...
Rabid dog exposures cause >99% of human rabies deaths world-wide. In developing countries, where dogs are the viral reservoir, the 30-50% vaccination coverage of dog populations is insufficient to break the disease transmission cycle. In addition, many vaccines currently used in developing countries fail to maintain detectable levels of neutralizing antibody. The poor vaccination coverage with...
Pre-exposure DNA vaccination protects non-human primates against rabies virus. Post-exposure protection of monkeys against rabies virus by DNA vaccination has not been attempted. Presumably, post-exposure experiments have not been undertaken because neutralizing antibody is usually slow to be induced after DNA vaccination. In this study, we initially attempted to accelerate the induction of neutralizing...
We have previously shown that Macaca fascicularis (Cynomologus) monkeys receiving a primary and either one or two booster rabies DNA vaccinations are protected against rabies virus. In this study, we determined whether monkeys that had been vaccinated only once via gene gun or intramuscularly (i.m.) with different concentrations of DNA would be protected against rabies virus challenge. Neutralizing...
Post-exposure anti-rabies vaccination for individuals who have not previously been immunized against rabies includes a cell culture-derived vaccine and a one time injection of rabies immune globulin. Recent studies have shown DNA vaccinations to be highly effective in rabies pre-exposure experiments, but post-exposure protection has not been achieved. This failure is likely due to the slow onset of...
Long-term levels of neutralizing antibody were evaluated in mice after a single immunization with experimental DNA or recombinant vaccinia virus (RVV) vaccines encoding the rabies virus glycoprotein (G), or the commercially available inactivated virus human diploid cell vaccine (HDCV). Anamnestic antibody titers were also evaluated after two booster immunizations with vaccines that were identical...
Adjuvants are known to strongly enhance immune responses generated by traditional vaccines, but less is known about the effects of adjuvants on vaccination with DNA. In this study, we investigated the use of the immunostimulant monophosphoryl lipid A (MPL(R)) as an adjuvant, and analyzed three routes of DNA vaccination to determine if this adjuvant could enhance anti-rabies virus neutralizing antibody...
Accell gene gun particle-mediated immunization with DNA encoding the glycoprotein gene of the challenge virus standard strain of rabies virus was evaluated for its ability to elicit protective levels of serum anti-rabies virus neutralizing antibody. Strong primary and booster neutralizing antibody responses were detected in mice following immunization with 2 μg of DNA coated on 2.6-μm gold beads...
Vaccination against virus infections has proven to be an effective strategy in the improvement of human health. In this study, we evaluated two plasmid DNA vaccines expressing the glycoprotein (G) gene of the challenge virus standard (CVS) rabies virus for their ability to elicit neutralizing antibody and protect BALB/cByJ mice against lethal rabies virus challenge. A single inoculation of 10 μg...
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