吸附无细胞百白破联合疫苗的安全性和免疫原性研究

Immunogenicity and safety analysis of an Adsorption Tetanus-Diphtheria-acellular Pertussis (DTaP) vaccine

目的评价某公司研制的吸附无细胞百白破联合疫苗(DTaP)的安全性和免疫原性。方法选择1 200名3~5月龄知情同意、无百白破疫苗接种史、无百日咳白喉破伤风病史、无百白破疫苗接种禁忌症的健康婴幼儿,按1∶1比例随机接种3针次试验疫苗和对照疫苗,每针次间隔1个月。在观察期内对受试者进行安全性观察,采集免前和全程免疫后第28d血清样本,进行免疫原性观察。结果免疫后试验组抗百日咳毒素(PT)、丝状血凝素(FHA)、白喉类毒素(DT)、破伤风类毒素(TT)抗体阳转率均>99%,与对照组相比,差异均无统计学意义(P值均>0.05),试验组非劣效于对照组。4种抗体几何平均浓度(GMC)试验组均高于对照组(P值均<0.01);抗体几何平均增长倍数(GMFI)除PT抗体外,其他3种抗体水平试验组均高于对照组(P值均<0.05)。两组全身和局部不良反应均以1级和2级为主,3级不良反应发生率均<2%,仅疲倦乏力、肿、疼痛等发生率试验组(2.17%~6.17%)高于对照组(0.67%~3.50%)(P值均<0.05)。结论该公司研制的吸附无细胞百白破联合疫苗与同类上市疫苗相比,免疫原性较好,不良反应轻微,安全性可以耐受,可进一步进行多联疫苗探索和研究。

Objective To evaluate immunogenicity and safety of a DTaP vaccine manufactured by company A.Methods A randomized,blinded,single-center and positive controlled clinical trial was conducted.A total of 1 200 healthy infants of age from 3to 5months old without vaccination history of DTaP,disease history or contraindidions were randomly assigned at the ratio of 1∶1to receive 3doses of test or positive control DTaP vaccines at 1 month interval with informed consent.The vaccine＇s safety was evaluated by observation;the immunogenicity was evaluated by analysis of serums collected before and after 28 dof inoculation.Results After vaccination,seroconversion rates of anti-PT,anti-FHA,anti-DT and anti-TT antibodies in test group were all over 99%and no significant difference or non-inferiority was observed compared with control group（all P〈0.05）.Compared to control group,GMC of 4antibodies were higher in test group（all P〈0.01）,while GMFI of antiFHA,anti-DT and anti-TT were higher in test group（all P〈0.05）.For both control group and test group,systemic and local adverse reactions were mainly grade 1and grade 2,the incidence of grade 3adverse reactions was less than 2%.Only pain,swelling and tiredness in test group had higher reported rates（2.17%-6.17%）than those in control group（0.67%-3.50%）,with statistical difference（all P〈0.05）.Conclusion Compared with commercial available vaccines on market,the test DTaP vaccine produced by company A has good immunogenicity and safety.Future research on multivalent combination vaccine should be carried out to develop vaccines with better performance.