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Effect of heterogeneity of rabies virus strain and challenge route on efficacy of inactivated rabies vaccines in mice

Peter S. WunderliRabies Laboratory, DVRD, NCID, and Animal Care Facility, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333.
Present address is Immunogen Inc, 128 Sidney St, Cambridge, MA 02139-4239.

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David W. DreesenRabies Laboratory, DVRD, NCID, and Animal Care Facility, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333.
Present address is Department of Medical Microbiology and Parasitology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Timothy J. MillerRabies Laboratory, DVRD, NCID, and Animal Care Facility, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333.
Present address is Benchmark Biolabs, 521 W Industrial Lake Dr, Lincoln, NE 68528.

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George M. BaerRabies Laboratory, DVRD, NCID, and Animal Care Facility, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333.
Present address is Laboratorios Baer, Adpo Postal 11-784, Mexico 11, DF, 06101, Mexico.

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Abstract

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)

Abstract

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)