脊髓灰质炎灭活疫苗加强免疫的免疫原性和安全性观察

Immunogenicity and safety of a booster dose of inactivated polio vaccine

目的 评价完成脊髓灰质炎灭活疫苗（inactivated polio vaccine,IPV）基础免疫的儿童,在18月龄进行IPV加强免疫的安全性和免疫原性.方法 2011至2012年选择在2、3、4月龄各接种1剂IPV完成基础免疫,并且在18月龄完成1剂IPV加强免疫接种的儿童,共有97名研究对象入组,检测加强免疫前、后的血清中脊髓灰质炎中和抗体,计算抗体几何平均滴度（GMT）和保护率.同时观察接种后30 d内发生的不良反应,包括局部疼痛、红肿、硬结,发热、呕吐、异常哭闹、嗜睡、食欲下降、易激惹,以及其他身体不适的所有症状和用药情况,对疫苗安全性进行描述性分析.结果 最终有84名调查对象完成了免疫前后的血清采样.加强免疫前,脊髓灰质炎Ⅰ型、Ⅱ型、Ⅲ型的中和抗体阳性率均为100％（84/84）,GMT（95％CI）分别为1∶148.5（116.49 ～ 189.29）、1∶237.68（178.39～316.67）、1∶231.87（181.27 ～ 296.58）；加强免疫后,3个型别中和抗体阳性率均为100％（84/84）,GMT（95％CI）分别为1∶1612.14（1470.57 ～ 1767.34）、1∶1854.92（1715.83 ～ 2005.29）、1∶1625.50（1452.12～ 1819.58）.加强免疫前,脊髓灰质炎Ⅰ型、Ⅱ型、Ⅲ型的中和抗体滴度分布集中于1∶128～1∶512范围内,分别占各型的65％ （55/84）、55％ （46/84）、74％ （62/84）.加强免疫后,3个型别中和抗体滴度升高,抗体≥1∶1024者分别占93％ （78/84）、95％（80/84）、92％ （77/84）.共有96名研究对象完成了安全性观察,16名出现不良反应,总发生率17％.观察到的局部反应主要为压痛3％ （3/96）,无红肿和硬结；全身反应分别为食欲下降8％（8/96）、易激惹8％（8/96）、发热7％（7/96）、异常哭闹6％（6/96）、嗜睡6％（6/96）、呕吐1％ （1/96）.所有反应均为轻度和中度；局部反应全部发生在接种当日,持续1 ～2d；全身反应多在接种后2d内发生,持续时间多小于3d.结论 IPV加强免疫具有良好的免疫原性和安全性,可提供有效的保护水平.

Objective To evaluate the immunogenicity and safety of a boost dose of inactivated polio vaccine （IPV） among children aged 18 months who had been administered with primary doses of IPV.Methods Form 2011 to 2012,a total of 97 children were enrolled in the present study who were vaccinated with IPV at 2,3,4 months of age and boosted with the same vaccine at 18 months of age.Antipoliovirus neutralizing antibody titers in serum were measured before and after booster vaccination,geometric mean titers （GMT） and seroprotection rate were calculated.Adverse events occurring within 30 days after booster vaccination were observed,including pain,redness/swelling and induration at the injection site,fever,vomit,abnormal crying,drowsiness,loss of appetite,irritability,and all other physical discomfort and related medications were also recorded.A descriptive analysis was performed for the safety assessment.Results Immunogenicity was assessed in 84 subjects.The pre-booster seropositivity rates of neutralizing antibody against poliovirus type 1,2,3 before booster were all 100％ （84/84） and the corresponding GMT（95％ CI）was 1∶ 148.5 （116.49-189.29）,1 ∶ 237.68 （178.39-316.67） and 1 ∶ 231.87 （181.27-296.58）,respectively.The seropositivity rates of neutralizing antibody against the three types of poliovirus after booster were all 100％ （84/84） and the corresponding GMT （95％ CI） was 1 ∶ 1612.14 （1470.57-1767.34）,1 ∶ 1854.92 （1715.83-2005.29） and 1 ∶ 1625.50 （1452.12-1819.58）,respectively.The pre-booster titer of neutralizing antibody against poliovirus type 1,2,3 mainly ranged 1∶128-1∶ 512,which accounted for 65％（55/84）,55％ （46/84）,74％ （62/84） in each type.After the booster immunization,titers of neutralizing antibody against type 1,2,3 were increased as subjects with titer ≥ 1∶1024 accounted for 94％ （78/84）,95 ％ （80/84）,92％ （77/84）,respectively.Safety was evaluated in 96 subjects,of which 16 subjects reported adverse events with the rate of 17％.The observed local events were mainly tenderness 3 ％ （3/96）,redness/swelling and induration were not reported.The systemic adverse events included loss of appetite（8％,8/96）,irritability （8 ％,8/96）,fever （7 ％,7/96）,abnormal crying （6 ％,6/96）,drowsiness （6％,6/96） and vomit （1％,1/96）.All reported adverse events were mild or moderate.All of the local events occurred in the day of vaccination and lasted for 1-2 days,while systemic events almost developed within 2 days after vaccination and last less than 3 days.Conclusion IPV booster dose has good immunogenicity and safety profile,which provides effective protection against poliovirus.