比利时安特卫普大学Pierre Van Damme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健康成人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。
目前已开发出两种新型2型口服脊髓灰质炎候选疫苗（OPV2），新型OPV2-c1和新型OPV2-c2，其设计上比获得许可的Sabin单价OPV2在遗传上更稳定，以应对由于疫苗衍生株脊髓灰质炎病毒循环引发的脊髓灰质炎大暴发。
研究组在比利时的两个中心做了两项随机研究。第一项是在OPV2全面撤销之前，在安特卫普进行的单价OPV2的临床4期历史对照研究；第二项是在安特卫普和根特进行的新型OPV2-c1和新型OPV2-c2的临床2期研究。
研究组招募18至50岁的健康成年人，至少有3次脊髓灰质炎疫苗接种的历史记录。在历史对照试验中，将参与者随机分配一剂或两剂单价OPV2。在新型OPV2试验中，先前接种过OPV疫苗的参与者被随机分配一剂或两剂新型OPV2-c1或新型OPV2-c2。
IPV疫苗接种的参与者被随机分配接受两种剂量的新型OPV2-c1、新型OPV2-c2或安慰剂。主要目标是评估和比较每次给药后长达28天的安全性，包括引起的不良事件和严重不良事件，以及单价OPV2和这两种新型OPV2候选疫苗之间的免疫原性（第一剂疫苗接种后第28天的血清保护率）。
在历史对照研究中，2016年1月25日至3月18日，研究组共招募了100名志愿者，并随机分配他们接受一或两剂单价OPV2，每组50例。在新型OPV2研究中，2018年10月15日至2019年2月27日，研究组将200名先前接种过OPV的志愿者分为四组，分别接种一或两剂新型OPV2-c1或新型OPV2-c2，每组50名；将另外50名先前接种IPV疫苗的参与者随机分配接种新型OPV2-c1（17名）、新型OPV2-c2（16名）或安慰剂（17名）。
所有参与者都接种了首剂指定疫苗或安慰剂的治疗，并被纳入总接种人群中。所有疫苗似乎都很安全。没有明确报道与疫苗相关的停药或严重的不良事件。在先前接种过OPV疫苗的参与者中首次给药后，单价OPV2接种者中有62名（62％）、新型OPV2-c1接种者中有71名（71％）、新型OPV2-c2接种者中74名（74％）发生全身性不良事件，其中各组分别有4例、3例和2例为严重不良事件。
在接种过IPV疫苗的参与者中，新型OPV2-c1接种者中有16名（94％）发生了招募性不良事件（1例严重），新型OPV2-c2接种者中有13名（81％，1例严重），安慰剂接种者中有15名（88％，2例严重）。在先前接种过OPV疫苗的参与者中，296名中的286名（97％）在基线时呈血清阳性；接种首剂后，100％的新型OPV2疫苗和97％的单价OPV2疫苗接种者血清呈阳性。
总之，在先前接种过OPV和IPV的成年人中，新型OPV2候选疫苗与单价OPV2一样安全、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 healthy adults: two clinical trials
Author: Ilse De Coster, Isabel Leroux-Roels, Ananda S Bandyopadhyay, Christopher Gast, Kanchanamala Withanage, Katie Steenackers, Philippe De Smedt, Annelies Aerssens, Geert Leroux-Roels, M Steven Oberste, Jennifer L Konopka-Anstadt, William C Weldon, Alan Fix, John Konz, Rahnuma Wahid, John Modlin, Ralf Clemens, Sue Ann Costa Clemens, Novilia S Bachtiar, Pierre Van Damme
Issue&Volume: 2020-12-09
Abstract:
Background
Two novel type 2 oral poliovirus vaccine (OPV2) candidates, novel OPV2-c1 and novel OPV2-c2, designed to be more genetically stable than the licensed Sabin monovalent OPV2, have been developed to respond to ongoing polio outbreaks due to circulating vaccine-derived type 2 polioviruses.
Methods
We did two randomised studies at two centres in Belgium. The first was a phase 4 historical control study of monovalent OPV2 in Antwerp, done before global withdrawal of OPV2, and the second was a phase 2 study in Antwerp and Ghent with novel OPV2-c1 and novel OPV2-c2. Eligible participants were healthy adults aged 18–50 years with documented history of at least three polio vaccinations, including OPV in the phase 4 study and either OPV or inactivated poliovirus vaccine (IPV) in the novel OPV2 phase 2 study, with no dose within 12 months of study start. In the historical control trial, participants were randomly assigned to either one dose or two doses of monovalent OPV2. In the novel OPV2 trial, participants with previous OPV vaccinations were randomly assigned to either one or two doses of novel OPV2-c1 or to one or two doses of novel OPV2-c2. IPV-vaccinated participants were randomly assigned to receive two doses of either novel OPV2-c1, novel OPV2-c2, or placebo. Vaccine administrators were unmasked to treatment; medical staff performing safety and reactogenicity assessments or blood draws for immunogenicity assessments were masked. Participants received the first vaccine dose on day 0, and a second dose on day 28 if assigned to receive a second dose. Primary objectives were assessments and comparisons of safety up to 28 days after each dose, including solicited adverse events and serious adverse events, and immunogenicity (seroprotection rates on day 28 after the first vaccine dose) between monovalent OPV2 and the two novel OPV2 candidates. Primary immunogenicity analyses were done in the per-protocol population. Safety was assessed in the total vaccinated population—ie, all participants who received at least one dose of their assigned vaccine. The phase 4 control study is registered with EudraCT (2015-003325-33) and the phase 2 novel OPV2 study is registered with EudraCT (2018-001684-22) and ClinicalTrials.gov (NCT04544787).
Findings
In the historical control study, between Jan 25 and March 18, 2016, 100 volunteers were enrolled and randomly assigned to receive one or two doses of monovalent OPV2 (n=50 in each group). In the novel OPV2 study, between Oct 15, 2018, and Feb 27, 2019, 200 previously OPV-vaccinated volunteers were assigned to the four groups to receive one or two doses of novel OPV2-c1 or novel OPV2-c2 (n=50 per group); a further 50 participants, previously vaccinated with IPV, were assigned to novel OPV2-c1 (n=17), novel OPV2-c2 (n=16), or placebo (n=17). All participants received the first dose of assigned vaccine or placebo and were included in the total vaccinated population. All vaccines appeared safe; no definitely vaccine-related withdrawals or serious adverse events were reported. After first doses in previously OPV-vaccinated participants, 62 (62%) of 100 monovalent OPV2 recipients, 71 (71%) of 100 recipients of novel OPV2-c1, and 74 (74%) of 100 recipients of novel OPV2-c2 reported solicited systemic adverse events, four (monovalent OPV2), three (novel OPV2-c1), and two (novel OPV2-c2) of which were considered severe. In IPV-vaccinated participants, solicited adverse events occurred in 16 (94%) of 17 who received novel OPV2-c1 (including one severe) and 13 (81%) of 16 who received novel OPV2-c2 (including one severe), compared with 15 (88%) of 17 placebo recipients (including two severe). In previously OPV-vaccinated participants, 286 (97%) of 296 were seropositive at baseline; after one dose, 100% of novel OPV2 vaccinees and 97 (97%) of monovalent OPV2 vaccinees were seropositive.
Interpretation
Novel OPV2 candidates were as safe, well tolerated, and immunogenic as monovalent OPV2 in previously OPV-vaccinated and IPV-vaccinated adults. These data supported the further assessment of the vaccine candidates in children and infants.
DOI: 10.1016/S0140-6736(20)32541-1
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32541-1/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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本期文章：《柳叶刀》：Online/在线发表
