美国新兴国家抗击传染病组Ricardo Rüttimann团队比较了两种新型2型口服脊髓灰质炎疫苗与单价2型口服脊髓灰质炎疫苗在儿童和婴儿中的安全性和免疫原性。2020年12月9日，该研究发表在《柳叶刀》杂志上。
来自Sabin口服脊髓灰质炎疫苗（OPV）的疫苗衍生株脊髓灰质炎病毒循环和与疫苗相关的麻痹性脊髓灰质炎的持续出现和传播，刺激了两种具有相似免疫原性的新型2型OPV候选疫苗（OPV2-c1和OPV2-c2）的研发，提高了遗传稳定性，并减少了获得神经毒性的风险。
为了评估在儿童和婴儿中与单价Sabin OPV相比，这两种新型OPV候选药物的安全性和免疫原性，研究组在巴拿马的健康儿童（1-4岁）和婴儿（18-22周）中进行了两项单中心、多机构、部分掩盖的随机试验。一项为在全球停止使用单价OPV2之前，单价Sabin OPV2的对照临床4期研究；一项为针对低剂量和高剂量的两种新型OPV2候选药物进行的临床2期研究。
所有参与者均接种过一次OPV2疫苗，并且间隔28天接种了两次剂量。参与者的父母报告了不良事件。在第0、7、28和56天测量2型脊髓灰质炎病毒中和抗体，并在接种后28天评估粪便病毒脱落状况。主要目标是评估所有参与者的安全性，以及新型OPV2第28天血清保护相对于婴儿单价OPV2的非劣效性。
对照研究于2015年10月23日至2016年4月29日进行，随后的临床2期研究于2018年9月19日至2019年9月30日进行。研究组共招募了150名儿童，其中对照研究50名，新型OPV2研究100名；以及684名婴儿，其中对照研究110名，新型OPV2研究574名，均至少接受了一次研究疫苗接种。
疫苗接种安全且耐受性良好，所有组均未发生疫苗相关的严重不良事件或重要医学事件。不论疫苗或剂量如何，不良事件均为轻度或中度。几乎所有儿童在基线时都受到血清保护，表明其具有较高的基线免疫力。
在儿童中，单价OPV2和两种新型OPV2候选药物在单次给药后28天的血清保护率均为100％。在婴儿中，接种单价OPV2后28天的血清保护率为94%，接种高剂量新型OPV2-c1后为94%，接种低剂量新型OPV2-c1后为93%，接种高剂量新型OPV2-c2后为95%，接种低剂量新型OPV2-c2后为91%。尽管单价OPV2接种者的基线免疫力较高，但低剂量和高剂量新型OPV2-c1，以及高剂量新型OPV2-c2均表现出非劣效性。
综上，两种新型OPV2候选疫苗在儿童和婴儿中都是安全的，耐受性良好且具有免疫原性。
附：英文原文
Title: Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in children and infants: two clinical trials
Author: Xavier Sáez-Llorens, Ananda S Bandyopadhyay, Christopher Gast, Tirza De Leon, Rodrigo DeAntonio, Jose Jimeno, Maria Isabel Caballero, Gabriela Aguirre, M Steven Oberste, William C Weldon, Jennifer L Konopka-Anstadt, John Modlin, Novilia S Bachtiar, Alan Fix, John Konz, Ralf Clemens, Sue Ann Costa Clemens, Ricardo Rüttimann
Issue&Volume: 2020-12-09
Abstract:
Background
Continued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin oral poliovirus vaccines (OPVs) has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants.
Methods
We did two single-centre, multi-site, partly-masked, randomised trials in healthy cohorts of children (aged 1–4 years) and infants (aged 18–22 weeks) in Panama: a control phase 4 study with monovalent Sabin OPV2 before global cessation of monovalent OPV2 use, and a phase 2 study with low and high doses of two novel OPV2 candidates. All participants received one OPV2 vaccination and subsets received two doses 28 days apart. Parents reported solicited and unsolicited adverse events. Type 2 poliovirus neutralising antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days post-vaccination. Primary objectives were to assess safety in all participants and non-inferiority of novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants (non-inferiority margin 10%). These studies were registered with ClinicalTrials.gov, NCT02521974 and NCT03554798.
Findings
The control study took place between Oct 23, 2015, and April 29, 2016, and the subsequent phase 2 study between Sept 19, 2018, and Sept 30, 2019. 150 children (50 in the control study and 100 of 129 assessed for eligibility in the novel OPV2 study) and 684 infants (110 of 114 assessed for eligibility in the control study and 574 of 684 assessed for eligibility in the novel OPV2 study) were enrolled and received at least one study vaccination. Vaccinations were safe and well tolerated with no causally associated serious adverse events or important medical events in any group. Solicited and unsolicited adverse events were overwhelmingly mild or moderate irrespective of vaccine or dose. Nearly all children were seroprotected at baseline, indicating high baseline immunity. In children, the seroprotection rate 28 days after one dose was 100% for monovalent OPV2 and both novel OPV2 candidates. In infants at day 28, 91 (94% [95% CI 87–98]) of 97 were seroprotected after receiving monovalent OPV2, 134 (94% [88–97]) of 143 after high-dose novel OPV2-c1, 122 (93% [87–97]) of 131 after low-dose novel OPV2-c1, 138 (95% [90–98]) of 146 after high-dose novel OPV2-c2, and 115 (91% [84–95]) of 127 after low-dose novel OPV2-c2. Non-inferiority was shown for low-dose and high-dose novel OPV2-c1 and high-dose novel OPV2-c2 despite monovalent OPV2 recipients having higher baseline immunity.
Interpretation
Both novel OPV2 candidates were safe, well tolerated, and immunogenic in children and infants. Novel OPV2 could be an important addition to our resources against poliovirus given the current epidemiological situation.
DOI: 10.1016/S0140-6736(20)32540-X
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32540-X/fulltext
LANCET：《柳叶刀》，创刊于1823年。隶属于爱思唯尔出版社，最新IF：202.731
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