| Epidemiological survey has shown that helminthic infections jeopardize the host's ability to generate protective immunity to HIV-1 and Mycobacterium tuberculosis after mass vaccination in developing countries, especialy in Africa and Southeast Asia. Beside the reasones of quality control, vaccinate route and method et al., Borkow and Bentwich suggested that helminth infections play a major role in this pathogenesis. And deworming could significantly improve the protective immunity against vaccine. Helmith infection could not only impair the protective immunity to HIV-1 and Mycobacterium tuberculosis but also reduce the tetanus toxoid-specific immune responses in human Schistosoma mansoni infection.Most areas where the vaccine has not performed well are characterized by high endemic prevalence of worm infections. Chronic helminth infections were characterized by skewing towards a T helper 2 type response. Several investigations suggest that distinctive T-helper-2-biased profile induced by the chronic helminth infections may have an infaust effect on the outcome of vaccinations of host and disappears after eradication of these infections.Hepatitis B is one of the most prevalent and harmest diseases all over the world. In China,60% population are infected with HBV, among them over 120 million persons are carriers, and almost 28 million patients are chronic cases.Vaccination is the most effective measure to control and prevent hepatitis B. Despite the extremely high efficacy of HBV-vaccines, about 10% of healthy recipients fail to generate protective levels of antibodies to the vaccine after standard immunization. The second generation of polypeptide vaccine at present has the same problem, too. This part of population are called no or low responder. Once exposed to HBV, these hyporesponders might be susceptible even develop into chronic carrier. Epidemiological investigations found that the non-or low-response rate to YDV in rural children is much higher than that in urban children in China (60.1% vs 5-10%). It's reported that region factor was one of the major influencing factores for protective efficacy of HBV vaccination. All these results demonstrated that rural children were the main nonresponse population. More research works are needed to prove whether the phenomenon is assiciated with helminth infections or not.Schistosomiasis is one of the world's most prevalent helminth infections including China. A predominantly T-helper-1 reaction in the early stages of Schistosoma infection shifts to an egg-induced T-helper-2-biased profile. Most areas, where the vaccine has not performed well, are characterized by high endemic prevalence of worm infections. Chronic helminth infections are characterized by skewing towards a T helper 2 type response in the hosts. Several investigations suggest that distinctive T-helper-2-biased profile induced by the chronic helminth infections may have an infaust effect on the outcome of vaccinations of host and this effects could disappear after eradication of these infections.Our results showed that a predominantly T-helper-1 reaction (IL-2 and IFN-γincreased) in the acute stages while an egg-induced T-helper-2-biased profile (IL-4 and IL-5 increased) in the chronic stages of S. japonicum infection. After vaccination, the pre-exist immunity background could not be eliminate or reversed. In addition, the serum levels of HBsAb and proliferation of splenocytes induced by HBsAg post-vaccination in chronic infections were significantly lower than those of control and of acute groups, respevtively. It suggested that the poor vaccination of YDV (include cellular immunity and humor immunity) was influenced by the Th2 biased background during S. japonicum infection. The levels of cytokines and of protective antibody decreased due to the poor immune responses of T and B cells.The T-helper-2-biased profile tapered slowly post-treatment by praziquantel (PZQ). The immune state in chronic infections (including the quantity of HBsAb in serum, proliferation of splenocytes induced by HBsAg, and cytokines levels in cultured supernatant of spleen cells stimulated by HbsAg) ameliorate gradually; especially at 16W after PZQ treatment in chronic infections, there was no significant difference compared to that of controls. Therefore, the results indicated that effective deworming could ameliorate the protective responses to YDV in experimental mice.In China, especially in rural area, helminth infections are widespread and of great variety. Re-infections are coomon, too. Thus, we should not depend only on helminthicide to improve the effect of vaccine. So, on the basic of our previous study, we studied the feasibility of IL-2 to take the place of deworming therapy. In our experiment,1000U rhIL-2 combined with YDV, could induce the higher levels of HBsAb in serum, but 3000U rhIL-2 plus with YDV could not enhance the HBsAg-specific humor immunity. Thus further research work are needed to invest the effect and dosage of rhIL-2 on vaccination of YDV in schistosomiasis prevalent areas. In conclusion, our data firstly demonstrated:1. The effect of YDV was influenced by S. japonicum infection and was associated with the different infection stages;2. The distinctive T-helper-2-biased profile induced by the chronic S. japonicum infection was the major infaust effect on the outcome of YDV vaccination;3. Effective helminthicide therapy could reverse the T-helper-2 polarization and improve the protective immunity of YDV;4. The representative management with IL-2 have potential feasibility to improve the protective immunity of YDV. |
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