[Immunoprophylaxis of rabies: current recommendations]. / L'immuno-prophylaxie de la rage: actualisation des recommandations.

Pre-exposure rabies vaccination should comprise 3 injections (day 0, day 7, day 28) followed by boosters 1 year later then every 5 years. Populations who are particularly exposed due to occupation, regular contact with animals in endemic areas during leisure activities or holidays should be vaccinated, especially if access to post-exposure treatment is difficult. Post-exposure treatment should comprise 5 injections (day 0, day 3, day 7, day 14, day 28) which must be given with specific immunoglobulins on day 0 if there are penetrating wounds. In persons whose prior vaccination status is well-documented and correctly maintained, post-exposure treatment may be limited to 2 injections on day 0 and day 3. The vaccine is given is intramuscular injection in the deltoid region. Immunoglobulins are used at the dose of 20 IU/kg for human immunoglobulins and at 40 IU/kg for horse immunoglobulins. The injections are infiltrated around the lesions and the remaining quantity injected in the gluteus muscle. Seroconversion must be monitored by assaying neutralizing antibodies (titre > or = 0.5 IU/ml with the RFFI Test) in vaccinated populations who regularly exposed. Monitoring can also be useful after post-exposure treatment in certain specific cases (immunosuppressed subjects, treatment protocol incorrectly or incompletely applied). An antibody titre under 0.5 IU/ml requires an immediate vaccine injection.

Nucleocapsid specific T and B cell responses in humans after rabies vaccination.

The importance of the immune response directed to the internal component of the rabies virus, the nucleocapsid (NC), was evaluated in humans after rabies vaccination. T cell activation was measured with a bulk proliferative assay and relative frequencies of circulating NC-specific PBL were calculated with the limiting dilution technique. Vaccinees were classified into two groups: NC responders and NC non-responders. In NC responders, the frequency of NC-specific circulating lymphocytes was up to 6 times higher than the frequency of virus-specific lymphocytes. In non-responders, NC-specific lymphocytes were up to 25 times less common than virus-specific ones. The NC capacity to induce a secondary antibody response was tested in vitro. After a stimulation with complete virus, lymphocytes originating from donors vaccinated with tissue culture vaccine produced a secondary antibody-response composed mainly of glycoprotein-specific neutralizing antibodies, whereas lymphocytes from suckling mouse brain vaccines produced essentially NC-specific antibodies. This result confirmed the serological status of suckling mouse brain vaccinees, who usually developed high titres of NC-specific antibodies. After an in vitro NC stimulation, lymphocytes collected from NC responders produced not only NC-specific antibodies, provided they have NC-specific B cells at the time of blood sampling, but most surprisingly, they also produce glycoprotein-specific neutralizing antibodies. This finding indicates that NC free of glycoprotein is capable, in some individuals, of boosting an heterologous glycoprotein response.

Safety and immunogenicity of combined rabies and typhoid fever immunization.

The prevalence of rabies and typhoid fever in many developing countries poses a serious health hazard to travellers. The development of a combined immunization schedule would be advantageous. A study was performed on 104 adult volunteers using purified Vero cell rabies vaccine and Typhim Vi, a purified capsular polysaccharide, either separately or in combination. No significant difference was observed in immunogenicity or tolerance between the two groups. A 3-year follow-up study is planned.

T and B cell human responses to European bat lyssavirus after post-exposure rabies vaccination.

T and B cell human responses to European bat lyssavirus (EBL1) induced by post-exposure rabies vaccination (PM virus vaccine) were evaluated by measuring plasmatic titres of EBL1-specific neutralizing antibodies; specific EBL1-binding antibodies; and proliferation indices of peripheral blood lymphocytes stimulated in vitro with EBL1. These parameters for vaccination efficacy were compared with those obtained with vaccine-related viruses (CVS and ERA) and with a non-vaccine-related virus. Mokola virus, the last implicated in vaccination failures. Twenty-two patients exposed to rabies risk who received a reduced rabies post-exposure vaccination were involved in the study. On day 21, vaccine induced CVS-specific neutralizing antibodies in all patients; but EBL1-specific neutralizing antibodies were induced in only 73% of patients. No vaccine had Mokola-specific neutralizing antibodies. Patients having EBL1-specific neutralizing antibodies were usually those in whom vaccination induced high titres of CVS-specific neutralizing antibodies. On day 21, peripheral blood lymphocytes of 86% of patients could be restimulated in vitro with vaccine, 43% with EBL1 and 45% with Mokola. Patients exhibiting a high vaccine-specific proliferation response more likely developed an EBL1- or a Mokola-specific proliferative response. No correlation was found between T and B cell responses. Rabies vaccination induced neither T nor B cell EBL1-specific responses in 22% of patients.

Rabies-specific production of interleukin-2 by peripheral blood lymphocytes from human rabies vaccinees.

Cell-mediated immunity induced by rabies vaccination was studied in humans by the determination of specific interleukin-2 (IL-2) production in a large number of donors (postexposure immunized patients and pre-exposure immunized laboratory workers). Peripheral blood lymphocytes (PBL) from 35 donors were tested for IL-2 production after in vitro stimulation by different rabies and rabies-related viruses. IL-2 responses were compared to antibody recognition of these different virus serotypes by sera from the same individuals. IL-2 was produced by PBL from more than 85% of donors after stimulation with inactivated and purified rabies viruses (IPRV) prepared from either Pittman Moore (PM) or Pasteur Virus (PV) strains. IL-2 was also produced by 65 and 45% of donor PBL stimulated with IPRV from the European Bat Lyssavirus (EBL) and Mokola (Mok) rabies-related virus strains respectively. No correlation was found between the production of IL-2 by PBL and the levels of virus neutralizing antibody (VNAb). Moreover, 50, 25 and 35% of donors produced IL-2 after stimulation of their PBL with ribonucleoprotein (RNP) from PV-, EBL- and Mok-viruses, respectively. These results obtained with a large number of human rabies vaccinees and using an assay specific to T-cell activation confirm the significant cross-reactivity of T-cell responses directed against rabies and rabies-related viruses. This study shows that IL-2 production could be used for the study of cell-mediated immunity and T-cell memory induced in humans by rabies vaccination.

[Meningoradiculitis after injection of an antirabies vaccine. A vaccine from human diploid cell culture]. / Méningo-radiculite secondaire à une vaccination antirabique. A partir d'un vaccin préparé sur culture de cellules diploïdes humaines.

We report the case of a 45-year old farmer who developed meningoradiculitis after preventive anti-rabies vaccination with a vaccine obtained from human diploid cell culture. Two weeks after the second injection of vaccine, the patient complained of sensory symptoms in the right half of his body. These symptoms spontaneously regressed. The literature is reviewed and the physiopathological hypotheses are discussed.