George M. Baer

One-year study of the 2-1-1 intramuscular postexposure rabies vaccine regimen in 100 severely exposed Thai patients using rabies immune globulin and Vero cell rabies vaccine

The 2-1-1 rabies postexposure treatment schedule is an abbreviated regimen in which a tissue culture rabies vaccine is administered intramuscularly at two sites on day 0, and at one site on days 7 and 21. Compared to the standard five-dose intramuscular regimen, the 2-1-1 schedule reduces the number of clinic visits from five to three and the amount of vaccine used by 20%. One hundred Thai patients, who were severely exposed to rabies, were treated with rabies immune globulin and the 2-1-1 regimen using purified Vero cell rabies vaccine. They were followed for 1 year. Rabies antibody titres were measured in 10% of this group. All patients survived and adverse reactions were mild. A satisfactory antibody response (a titre greater than 0.5 IU ml-1) occurred in all ten patients studied at day 14, but persisted for 90 days in 80% and for 360 days in only 50%. The authors therefore do not recommend use of the 2-1-1 schedule in severely exposed patients who also need to receive rabies immune globulin.

The protective role of humoral neutralizing antibody in the NIH potency test for rabies vaccines

Intraperitoneal vaccination of mice with rabies vaccine results in both dosage-dependent rabies virus neutralizing antibody titres and protection from lethal intracerebral (i.c.) challenge with fixed strain CVS rabies virus. Pre-exposure adoptive intravenous transfer of naive or immune cells did not significantly protect naive Balb/c mice from lethal i.c. CVS challenge, but immune serum and anti-rabies glycoprotein monoclonal antibodies (individually and in combination) did confer significant protection when administered before or up to 24 h after lethal i.c. rabies virus challenge.

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%) were rabid. Of 1,675 mongooses tested for rabies serum neutralizing (SN) antibody, 498 (30%) were positive. During these four years (1971-74) the antibody prevalence rate increased from 20.8% to 43.2%, whereas the number of rabid mongooses decreased from 3.5% to 0.6%. 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 greatest in mongooses with high initial titres. High titres of naturally acquired 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(1.8) to 10(4.3) and, in some cases, were only slightly lower than those of salivary gland tissue (range, 10(1) to 10(5.6).

Oral rabies vaccination of arctic foxes (Alopex lagopus) with an attenuated vaccine.

Arctic foxes were immunized with the SAG1 oral rabies vaccine. The effectiveness was determined by the serological response and by the survival to a challenge dose of rabies virus from an Alaskan fox. Vaccine virus was isolated from saliva 1 h after the liquid vaccine was placed directly into the mouth but not subsequently (tested up to 1 week postvaccination). Two weeks after vaccination, protective antibody levels were present in all foxes and all vaccinated foxes survived challenge at 9 weeks postvaccination. At 26 weeks postvaccination (17 weeks postchallenge) all but one fox had detectable antibody levels. Neural tissue harvested from surviving foxes was negative for rabies virus by direct immunofluorescent testing. One of the foxes vaccinated with SAG1 seroconverted and survived challenge even though the titre of the vaccine used was almost 4 logs less than that used to vaccinate the other foxes. These results suggest that the avirulent SAG1 oral rabies vaccine is very effective in protecting arctic foxes.

Serum neutralizing antibody after rabies postexposure prophylaxis.

One hundred seventy-seven persons submitted specimens for serum neutralizing antibody titer detreminations 30 to 90 days after starting postexposure rabies prophylaxis. Ninety-two percent of those who received duck embryo vaccine alone developed adequate antibody titers. However, 23% of those who received equine antirabies serum plus duck embryo vaccine failed to develop an adequate antibody titer; one of these inadequate responders subsequently died of rabies. Factors that increased the risk of a poor antibody response included the receipt of steroids during the course of postexposure prophylaxis, and the use of more than 55 lu/kg of equine antirabies serum. Many persons receiving postexposure rabies prophylaxis fail to develop adequate humoral immunity and may have an increased risk of developing rabies. We suggest that persons receiving postexposure rabies prophylaxis should have serum neutralizing antibody determinations 30 to 40 days after starting treatment.

Immunogenicity of rabies vaccines used during an urban epizootic of rabies in Mexico

From 1 July 1987 to 31 December 1988, 30% of 247 rabid dogs in Hermosillo, Mexico had a positive history of rabies vaccination. Serosurveys suggested that inactivated suckling mouse brain vaccine (INACT-SMBV) and inactivated tissue culture vaccine (INACT-TC) used before and during the epizootic were poor immunogens. Prospective studies showed that only about one-third of dogs vaccinated with INACT-SMBV were seropositive 5 weeks after vaccination. Lack of vaccine potency was the most likely cause of poor immunogenicity. Rabies vaccines should be evaluated periodically by measuring antibody responses in animals. In some circumstances, minimum seroconversion rates and antibody titres in vaccinated animals may be better measures of immunogenicity than relative potency.