The rabies peripheral challenge test: more accurate determination of vaccine potency.

The National Institutes of Health (NIH) rabies vaccine potency test is used internationally for evaluating the efficacy of inactivated rabies vaccines, despite concerns about its methods. An alternative test has been developed, using a simplified in vivo method for rabies vaccine testing which has several advantages over the currently recommended method of efficacy testing. The rabies peripheral challenge test more closely models practical vaccine application in target species; decreases the observed effect of vaccine virus strain in testing results and allows sensitive analysis of vaccine and production lot testing.

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

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.

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

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.

Rabies serum neutralizing antibody in mongooses from Grenada

During a four year study on Grenada, 4,754 mongooses were examined, of which 100 (2.1 percent) were rabid. Of 1,675 mongooses tested for rabies serum neutraslizing (SN) antibody, 498 (30 percent) were positive. During these four years (1971-74) the antibody prevalence rate increased from 20.8 percent to 43.3 percent, whereas the number of rabid mongooses decreased from 3.5 percent to 0.6 percent. Naturally acquired antibody was monitored in 20 captive mongooses for up to 35 months, and it was still circulating in 18 when monitoring ceased. The highest titre recorded was 1:1,400, and the rate of fall was highest in mongooses with high initial titres. High titres of naturally occuring antibody suggest recent rabies activity. 14 mongooses vaccinated parenterally with 1.0 ml of attenuated ERA vaccine showed substantial increases in antibody titres; most had titres greater than 1:1,000 one month later and maintained a high titre for several months. The highest recorded was 1:34,800. The virus titres of brain material from rabid mongooses ranged from 10 to the power 1.8 to 10 to the power 4.3 and, in some cases, were only slightly lower than those of salivary gland tissue (range 10 to the power 1 to 10 to the power 5.6) (Summary)