吸附无细胞百日咳-白喉-破伤风-乙型肝炎-Sabin株灭活脊髓灰质炎联合疫苗的免疫持久性

Immune persistence of diphtheria,tetanus,accellular pertussis,hepatitis B and inactivated poliovirus (Sabin strain) combined vaccine

目的观察不同剂量配比及制备工艺的吸附无细胞百日咳-白喉-破伤风-乙型肝炎-Sabin株灭活脊髓灰质炎联合疫苗(DTa P-Hep B-s IPV)免疫大鼠后的免疫持久性。方法以中、低剂量s IPV与铝佐剂相互配伍的不同配方设计4个DTa P-Hep B-s IPV实验组,即中剂量含铝佐剂s IPV组(A组)、中剂量不含铝佐剂s IPV组(B组)、低剂量含铝佐剂s IPV组(C组)、低剂量不含铝佐剂s IPV组(D组),并设各组分相应的对照组和上市联合疫苗的参考组。以已完成3剂DTa P-Hep B-s IPV全程基础免疫的Wistar大鼠为研究对象,在全程基础免疫后第1、2、4、7、10、12个月釆血,检测各组大鼠血清中各组分抗体阳性率及抗体水平(GMT值)。结果基础免疫后观察全程,A组各型别脊灰病毒中和抗体阳性率持续保持在100%,B组为90%~100%,C组为80%~100%,D组为55.6%~100%。A、C组所诱导的各型别脊灰病毒中和抗体GMT均高于同等剂量不含铝佐剂的B、D组,且均达到或超过参考组;B、D组所诱导的Ⅰ型脊灰病毒中和抗体GMT均低于同等剂量的相应对照组,但Ⅱ、Ⅲ型脊灰病毒中和抗体GMT均能达到同等剂量相应对照组的水平。各组百白破抗体阳性率在观察全程均为100%,GMT与对照组相比总体上差异无统计学意义(P>0.05)。全程基础免疫后第12个月,乙肝抗体阳性率B组为70%、乙肝对照组为55.6%、A组为50%、C组为42.9%、D组和上市疫苗参考组均为30%,各组Anti-HBs Ag水平两两相比差异均无统计学意义(P>0.05)。结论 s IPV中剂量含铝佐剂的DTa P-Hep B-s IPV所诱导的各组分抗体水平较稳定持久,可作为未来疫苗配比的参考。

Objective To observe the immune persistence of diphtheria, tetanus, acellular pertussis, hepatitis B and inactivated poliovirus（Sabin strain）combined vaccine（DTa P-Hep B-s IPV）prepared at various ratios of dosages by various procedures. Methods Four experimental groups of DTa P-Hep B-s IPV vaccine were designed in this study based on aluminum adjuvant and the dosage of s IPV. The s IPV in group A was at a moderate dosage and contained aluminum adjuvant, while that in group B was at a moderate dosage and contained no aluminum adjuvant, that in group C was at a low dosage and contained aluminum adjuvant, and that in group D was at a low dosage and contained no aluminum adjuvant, using the corresponding components or a licensed vaccine as control. Wistar rats immunized with three doses of DTa P-Hep B-s IPV were used as experimental animals, of which the blood samples were collected in months 1, 2, 4, 7, 10 and 12 after full course primary immunization, and determined for the positive conversion rates and GMTs of antibodies against various components. Results The neutralizing antibody positive rates against poliovirus in groups A, B, C and D were 100%, 90% ~ 100%, 80% ~ 100% and 55. 6% ~ 100% respectively. However, the GMTs of neutralizing antibodies against poliovirus of various types in groups A and C were higher than those in groups B and D, which reached or exceeded the levels in licensed vaccine control group. The GMTs of neutralizing antibody against poliovirus type Ⅰ in groups B and D were lower than those in the corresponding control groups, while those against types Ⅱ and Ⅲ reached the level in the corresponding control groups. All the antibody positive rates against diphtheria, tetanus and pertussis were100% after primary immunization, while the GMTs showed no significant difference with those in control group in general（P〈0. 05）. The positive rates of anti-HBs Ag in months 12 after primary immunization were 70% in group B, 55. 6% in hepatitis B vaccine control group, 50% in group A, 42. 9% in group C, and both 30% in group D and licensed vaccine control group. However, the anti-HBs Ag levels showed no significant difference between various groups（P〈0. 05）.Conclusion Aluminum adjuvant-containing DTa P-Hep B-s IPV at a moderate dosage of s IPV induced persistent antibody levels against various components, which provided a reference for formulation of vaccine in future.