Immunogenetical Approach to Side Reactions After Petussis Vaccination

无细胞百日咳疫苗自1981年以来一直在日本全国范围内使用。该疫苗含有百日咳毒素(PT)和丝状血凝素(FHA)作为主要保护性抗原，注射时反应性较低。但接种疫苗后仍经常会出现一些不良反应。为了找出副反应发生的机制，从疫苗接种者的免疫遗传背景出发进行了探讨。为探讨人类白细胞抗原(HLA)在百日咳疫苗接种后副反应易感性中的作用，本研究采用小鼠模型。用这些保护性抗原和(或)用转座子Tn5插入技术制备的PT或FHA缺失的百日咳突变株免疫不同H-2单倍型的近交系小鼠，然后用强毒百日咳杆菌脑内或气雾攻击。观察感染小鼠的死亡数、体重增长、外周血白细胞计数、对组胺敏感性的增加。通过小鼠感染试验，观察H-2单倍型对百日咳杆菌的易感性和免疫应答。发现H-2d小鼠对百日咳杆菌感染最敏感，而H-2b小鼠对百日咳杆菌感染最不敏感。对PT和/或FHA的抗体反应与小鼠品系有关，即H-2单倍型。由于百日咳疫苗接种后观察到的局部反应部分归因于无细胞百日咳疫苗中的活性PT，这提示人类的人类白细胞抗原可能参与了无细胞百日咳疫苗免疫后副反应的易感性。需要进一步的临床和流行病学研究，以找出人类白细胞抗原分型与每一例副反应病例的相关性。

Acelluar pertussis vaccine has been used nationwide since 1981 in Japan. This vaccine contains pertussis toxin (PT) and filamentous hemagglutinin (FHA) as major protective antigen, and is found to be less reactogenic when injected. But still some unfavorable side reactions have been often experienced after vaccination. In order to find the mechanism by which side reaction occur, an approach has been made from standpoint of vaccinee's immunogenetical background. In order to investigate the possible involvement of HLA in the liability to side reactions after pertussis vaccination, mouse model waw adopted in the present study. Inbred strain mice of different H-2 haplotype were immunized with these protective antigens and/or B. pertussis mutant lacking in PT or FHA production which had been prepared by transposon Tn5 insertion technique, and then intra-cerebrally or aerosolly challenged with virulent B. pertussis . Infected mice were monitored by number of death, gain in body weight, peripheral WBC count, increased sensitivity to histamine.Through mouse infection tests, H-2 haplotype-related susceptibility to B. pertussis and immune response were observed. It was found that H-2d mice was the most susceptible strain, whereas H-2b was the least susceptible strain to B. pertussis infection. It was also suggested that antibody response toPT and or FHA was related to mouse strain, i. e, H-2 haplotype. As some of the local reaction observed after pertussis vaccination has been ascribed to active PT in acellular pertussis vaccine, this suggests that HLA in humans might be involved in liability to side reactions after immunization of acelluar pertussis vaccine. Further clinical and epidemiological study are required to find the correlation between HLA typing and each case with side reactions.