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  • Author or Editor: Peter S. Wunderli x
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Objective—To evaluate the effect of various routes of administration and number of doses of 3 commercially produced rabies vaccines on serum antibody responses and protection in mice challenged by intracerebral injection with fixed-strain rabies virus.

Animals—2,213 mice.

Procedure—Inactivated, adjuvanted rabies vaccines were administered to mice in either 2, 1, or 0 (control) doses via IP, IM, and SC routes, and mice were challenged intracerebrally with fixed-strain rabies virus.

Results—Vaccination route and dose number significantly influenced serum antibody responses and protection from rabies virus challenge, independent of vaccine strain origin and mouse strain, although mouse age significantly affected results. Extended challenge studies revealed that IM vaccination of mice resulted in the highest serum neutralizing antibody responses and protection levels equivalent to IP vaccination. Even multiple doses administered SC (a vaccination route used in dogs) resulted in poor serum anti-rabies neutralizing antibody responses in mice and were far less protective than other routes.

Conclusions and Clinical Relevance—Findings suggest possible improvements for the current rabies vaccine potency test in mice by using 1 dose, the IM route, and a delayed time of challenge. These modifications would more closely model vaccination practices in target species and yield more accurate information regarding primary immunogenicity of a vaccine. (Am J Vet Med 2003;64:491–498)

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in American Journal of Veterinary Research


Objective—To determine effect of route of challenge and strain of rabies virus on efficacy of inactivated rabies vaccines in mice.

Animals—3,056 mice.

Procedure—Challenge was performed with fixed and street rabies virus strains by use of footpad and intracerebral routes as well as IM injection into the hip, shoulder, neck, and masseter muscles. Intraperitoneal and IM vaccination was performed with 1 or 2 doses of 1 of 3 vaccine-strain inactivated rabies vaccines. For 2 of the vaccine strains, the vaccines were adjuvanted and nonadjuvanted.

Results—Incubation periods were dependent on route, dose, and virus strain used for challenge. Use of an intramasseter challenge route with challenge virus-strain rabies virus, which more accurately models natural exposure to rabies virus, resulted in reproducible mortality rates in mice. Use of this route revealed that differences among vaccines and challenge virus strains affected mortality rate less than that observed in the National Institutes of Health potency test, even when street isolates of widely variant origin were used for challenge.

Conclusions and Clinical Relevance—These results, combined with earlier data, support a proposal for a new rabies potency test that more closely models current vaccine administration practices and natural infection routes. (Am J Vet Res 2003;64:499–505)

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in American Journal of Veterinary Research