■萨宾灭活和二价口服脊髓灰质炎病毒疫苗(sIPV,bOPV)自2016年以来在中国普遍使用。我们进行了一个开放标签,随机化,对照4期试验,以评估sIPV或bOPV序贯免疫后的免疫持久性,4岁儿童加强剂量脊髓灰质炎病毒疫苗的免疫原性和安全性。
■先前临床试验的参与者在2、3和4个月时使用sIPV(I)或bOPV(B)进行了三种不同的序贯时间表(I-B-B组,I-I-B,I-I-I)在2017年被跟进。在I-B-B组给予sIPV后,将儿童进一步分为五个亚组,I-I-B组和I-I-I组随机给予sIPV或bOPV(I-B-B-I组中的128名儿童,I-I-B-B组60人,64在I-I-B-I组中,68在I-I-I-B组中,67在I-I-I-I组中)。通过测量脊髓灰质炎病毒类型特异性抗体来评估免疫持久性和免疫原性。对所有接受加强剂量的儿童进行安全性分析.
■在2020年12月5日至2021年6月30日之间,我们分别在免疫持久性分析中招募了381名参与者,和352名参与者参与了加强免疫的免疫原性分析。初次免疫四年后,抗脊髓灰质炎病毒1型和3型抗体的血清阳性率均>90%,而2型脊髓灰质炎病毒为46.83%,75.41%,I-B-B组为90.23%(χ2=60.948,P<0.001),I-I-B,而我-我-我,分别。加强剂量后,I-B-B-I组中所有三种血清型的血清阳性率均为100%,I-I-B-I和I-I-I-I;在I-I-B-B和I-I-I-B组中,1型和3型的血清阳性率均为100%,2型为92.59%和98.46%。对脊髓灰质炎病毒1和3的几何平均滴度(GMTs)在五组中都很高(>1860.73),在bOPV增强组中,针对2型的GMT显着降低:I-I-B-B组(50.60)和I-I-I-B组(247.84)。I-I-B-I组和I-I-I-I组三种血清型的血清阳性率或GMTs均无显着差异(P>0.05)。研究期间未发生严重不良事件。
■我们的研究结果表明,在目前的常规脊髓灰质炎病毒免疫接种计划中至少需要两次sIPV剂量,与中国目前的sIPV-sIPV-bOPV-bOPV时间表相比,包含3或4剂sIPV的时间表提供了更好的针对2型脊髓灰质炎病毒的保护。
■浙江省医药卫生科技(2021KY118)。该试验在ClinicalTrials.gov(NCT04576910)注册。
UNASSIGNED: Sabin inactivated and bivalent oral
poliovirus vaccine (sIPV, bOPV) were commonly used in
China since 2016. We conducted an open-label, randomised, controlled phase 4 trial to assess immune persistence following sequential immunisation with sIPV or bOPV, and immunogenicity and safety of a booster dose of poliovirus vaccine in children aged 4 years.
UNASSIGNED: Participants from a previous clinical trial with three different sequential schedules with sIPV (I) or bOPV (B) at ages 2, 3, and 4 months (Groups I-B-B, I-I-B, I-I-I) in 2017 were followed-up. The children were further divided into five subgroups after sIPV was given for Group I-B-B, and sIPV or bOPV randomly given for Group I-I-B and Group I-I-I (128 children in Groups I-B-B-I, 60 in Group I-I-B-B, 64 in Group I-I-B-I, 68 in Group I-I-I-B, 67 in Group I-I-I-I). Immune persistence and immunogenicity were assessed by measuring
poliovirus type-specific antibodies, and safety were analysed in all children who received the booster dose.
UNASSIGNED: Between Dec 5, 2020 and Jun 30, 2021, we respectively enrolled 381 participants in the immune persistence analysis, and 352 participants in per protocol (PP) analysis of the immunogenicity of the booster immunisation. Seropositivity rates of antibodies against poliovirus types 1 and 3 were all >90% four years after primary immunisation, while for poliovirus type 2 were 46.83%, 75.41%, and 90.23% (χ2 = 60.948, P < 0.001) for Groups I-B-B, I-I-B, and I-I-I, respectively. After the booster dose, seropositivity rates were 100% for all three serotypes in Group I-B-B-I, I-I-B-I and I-I-I-I; In Group I-I-B-B and I-I-I-B, the seropositivity rates for types 1 and 3 were all 100%, for type 2 were 92.59% and 98.46%. The geometric mean titres (GMTs) against
poliovirus 1 and 3 were all high in five groups (>1860.73), and the GMTs against type 2 were significantly lower in groups booster with bOPV: Group I-I-B-B (50.60) and Group I-I-I-B (247.84). There was no significant difference in seropositivity rates or GMTs for all three serotypes (P > 0.05) between Group I-I-B-I and I-I-I-I. No serious adverse events occurred during the study.
UNASSIGNED: Our findings suggest that at least two sIPV doses are needed in the current routine poliovirus immunisation schedule, and schedules containing 3 or 4 doses of sIPV provide better protection against poliovirus type 2 than the current sIPV-sIPV-bOPV-bOPV schedule in
China.
UNASSIGNED: Medical and Health Science and Technology of Zhejiang Province (2021KY118). This trial was registered with ClinicalTrials.gov (NCT04576910).