兩種新型2型口服脊髓灰質炎疫苗在健康成人中安全性高
作者：
小柯機器人發布時間：2020/12/14 15:17:18
比利時安特衛普大學Pierre Van Damme團隊比較了兩種新型2型口服脊髓灰質炎疫苗與單價2型口服脊髓灰質炎疫苗在健康成人中的安全性和免疫原性。2020年12月9日，該研究發表在《柳葉刀》雜誌上。
目前已開發出兩種新型2型口服脊髓灰質炎候選疫苗（OPV2），新型OPV2-c1和新型OPV2-c2，其設計上比獲得許可的Sabin單價OPV2在遺傳上更穩定，以應對由於疫苗衍生株脊髓灰質炎病毒循環引發的脊髓灰質炎大暴發。
研究組在比利時的兩個中心做了兩項隨機研究。第一項是在OPV2全面撤銷之前，在安特衛普進行的單價OPV2的臨床4期歷史對照研究；第二項是在安特衛普和根特進行的新型OPV2-c1和新型OPV2-c2的臨床2期研究。
研究組招募18至50歲的健康成年人，至少有3次脊髓灰質炎疫苗接種的歷史記錄。在歷史對照試驗中，將參與者隨機分配一劑或兩劑單價OPV2。在新型OPV2試驗中，先前接種過OPV疫苗的參與者被隨機分配一劑或兩劑新型OPV2-c1或新型OPV2-c2。
IPV疫苗接種的參與者被隨機分配接受兩種劑量的新型OPV2-c1、新型OPV2-c2或安慰劑。主要目標是評估和比較每次給藥後長達28天的安全性，包括引起的不良事件和嚴重不良事件，以及單價OPV2和這兩種新型OPV2候選疫苗之間的免疫原性（第一劑疫苗接種後第28天的血清保護率）。
在歷史對照研究中，2016年1月25日至3月18日，研究組共招募了100名志願者，並隨機分配他們接受一或兩劑單價OPV2，每組50例。在新型OPV2研究中，2018年10月15日至2019年2月27日，研究組將200名先前接種過OPV的志願者分為四組，分別接種一或兩劑新型OPV2-c1或新型OPV2-c2，每組50名；將另外50名先前接種IPV疫苗的參與者隨機分配接種新型OPV2-c1（17名）、新型OPV2-c2（16名）或安慰劑（17名）。
所有參與者都接種了首劑指定疫苗或安慰劑的治療，並被納入總接種人群中。所有疫苗似乎都很安全。沒有明確報導與疫苗相關的停藥或嚴重的不良事件。在先前接種過OPV疫苗的參與者中首次給藥後，單價OPV2接種者中有62名（62％）、新型OPV2-c1接種者中有71名（71％）、新型OPV2-c2接種者中74名（74％）發生全身性不良事件，其中各組分別有4例、3例和2例為嚴重不良事件。
在接種過IPV疫苗的參與者中，新型OPV2-c1接種者中有16名（94％）發生了招募性不良事件（1例嚴重），新型OPV2-c2接種者中有13名（81％，1例嚴重），安慰劑接種者中有15名（88％，2例嚴重）。在先前接種過OPV疫苗的參與者中，296名中的286名（97％）在基線時呈血清陽性；接種首劑後，100％的新型OPV2疫苗和97％的單價OPV2疫苗接種者血清呈陽性。
總之，在先前接種過OPV和IPV的成年人中，新型OPV2候選疫苗與單價OPV2一樣安全、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