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Effects of vaccine route and dosage on protection from rabies after intracerebral challenge in mice

Peter S. WunderliImmunogen Inc, 128 Sidney St, Cambridge, MA 02139-4239.

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David W. DreesenDepartment of Medical Microbiology and Parasitology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Timothy J. MillerBenchmark Biolabs, 521 W Industrial Lake Dr, Lincoln, NE 68528.

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George M. BaerLaboratorios Baer, Adpo postal 11-784, Mexico 06101 DF, Mexico.

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Abstract

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)

Abstract

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)