Effect Of Rabies Immunoglobulin By Systemic Injection On The Immune Efficacy Of Rabies Vaccine

Rabies is an acute zoonotic infectious disease that is caused by the rabies virus,which leads to central nervous system(CNS)dysfunction,and the mortality rate is almost 100%.It is necessary to accept post-exposure prophylaxis(PEP)immediately once a person or an animal is bitten which is the only effective treatment available currently.The dosage of irmmunoglobulin is 40 IU/Kg body weight in case of equine rabies immunoglobulin(ERIG)and 20 IU/Kg body weight in case of human rabies immunoglobulin(HRIG).Besides local infiltration into or around the wound site or sites,the remaining product,if any,should be injected intramuscularly at a site distant from the site of vaccine administration,and the first dose of the vaccine should be inoculated at the same time as the immunoglobulin,but in a different part of the body.As RIG can inhibit the viral invasion from the peripheral site to the nervous system,the role of RIG via local injection in passive immunization is to provide neutralizing antibodies at the site of the exposure before patients can begin producing their own antibodies physiologically after vaccination.An adult with a weight of 50 kg requires the injection of almost 10 ml of RIG via local infiltration and systemic injection according to this calculation method,and in many patient with wounds on the toes or finger tips,most of the RIG is administered via systemic injection.However,the human rabies immunoglobulins are very expensive and cannot be widely used across the developing world.Taking into account the above points,we simulated the III level after exposure to the effects of different doses and different parts of the injection of rabies vaccine combined with immunoglobulin on rabies specific antibody and neutralizing antibodies,to determine the systemic injection of RIG in the role of rabies vaccine.We simulated the III level of exposure prevention after immunization of mice at different injection sites,first of all,to the same amount of RIG and rabies vaccine in mice,detected the level of IL-4 and IFN-? in the serum by enzyme linked immunosorbent assay(Enzyme-linked Immunosorbent Assay,ELISA).The rapid fluorescent focus inhibition test(Rapid Fluorescent Focus Inhibition Test,RFFIT)detected neutralizing antibody titers in serum.Then in the same place with different doses of RIG,the titer of the specific antibody in the serum and neutralizing antibodies were detected by ELISA and RFFIT methods,to study the effect of RIG by systemic injection in mice on non specificity and adaptive immune.The results showed that the level of cytokine production was detected by ELISA that injected into different parts of mice have no difference with the contral group.The neutralizing antibody titers in serum that detected by RFFIT,all mice in seventh were positive,the neutralizing antibody titer of the mixed injection group(premixed the rabies immunoglobulin and rabies vaccine),significantly lower than the ipsilateral injection group and contral group,indicating RIG and rabies vaccine should not be mixed,the immune protective effect of rabies vaccine play a role after 7 days.There is no significant difference between the control group with the experimental groups.Suggest that the different injection sites of RIG have no significant effect on the cellular immunity and humoral immunity in rabies vaccine.The results of different doses of RIG injection detected by ELISA showed that the titer of antibody in serum of mouse which the injection of RIG is0.2IU is 0.49EU/ml in first days,the titer of antibody in serum of mice which were injected with the lowest dose of 0.05IU RIG in first days reached 0.37EU/ml.However,the antibody titers of mice immunized with rabies vaccine at different doses were all below the positive threshold(0.6 EU/ml).The neutralizing antibody titers in serum detected by RFFIT results show that 7 days after the first immunization,all 6 groups of mice were positive,the titer of neutralizing antibody in the serum of more than 0.5IU/ml,the immune response to rabies vaccine produced and the antibody titers between seventh days and fourteenth days increased significantly,the 6 groups did not mean variance analysis significant difference.The results showed that the different doses of RIG had no significant influence on the non specific,specific immunity and adaptive immunity of rabies vaccine.Overall our results in ? post exposure prophylaxis,injection site and injection dose in systemic injection of RIG has no significant influence on rabies vaccine nonspecific immunity,"cellular immunity and humoral immunity effect.The results suggest that the main role in the prevention of RIG treatment in ? after exposure is to neutralize the rabies virus around the wound immediately,and there were no effects on neutralizing antibodies in the serum.