Choi Won Suk, Noh Ji Yun, Song Joon Young, Cheong Hee Jin, Wie Seong-Heon, Lee Jin Soo, Lee Jacob, Kim Shin-Woo, Jeong Hye Won, Jung Sook-In, Kim Yeon-Sook, Woo Heung Jeong, Kim Kyung Ho, Kim Hun, Kim Woo Joo
a Division of Infectious Diseases, Department of Internal Medicine , Korea University College of Medicine , Seoul , Republic of Korea.
b Division of Infectious Diseases, Department of Internal Medicine , St. Vincent's Hospital, College of Medicine, The Catholic University of Korea , Seoul , Republic of Korea.
Hum Vaccin Immunother. 2017 Jul 3;13(7):1653-1660. doi: 10.1080/21645515.2017.1297351. Epub 2017 Apr 13.
The influenza B virus has two lineages; Yamagata and Victoria. The two lineages are antigenically distinct and it is difficult to expect cross-protection between the lineages. Actually, the mismatch between circulating influenza B viruses and vaccine strains has been occurred frequently. The cell-culture system for the production of influenza vaccine can contribute to improve vaccine strain selection and expand vaccine supplies. We investigated the immunogenicity and safety of cell culture-derived quadrivalent inactivated influenza vaccine (NBP607-QIV) in adults and elderly subjects.
A randomized controlled phase III trial was undertaken in 10 university hospitals in the Republic of Korea (Clinical trial Number-NCT02467842). Adults (aged 19-59 years) and elderly subjects (aged ≥60 years) were randomly assigned in a 2:1:1 ratio to NBP607-QIV versus cell culture-based trivalent inactivated influenza vaccine-Yamagata (NBP607-Y) and cell culture-based trivalent inactivated influenza vaccine-Victoria (NBP607-V). Immunogenicity was assessed 3 weeks after vaccination by hemagglutination inhibition assay. Safety was assessed for 6 months post-vaccination: solicited adverse events (AEs) for 7 days, unsolicited AEs for 21 days and serious adverse events (SAEs) for 6 months. AEs were sub-classified as adverse drug reactions (ADRs) according to the causality.
A total of 1,503 participants were randomly assigned to NBP607-QIV (n = 752), NBP607-Y (n = 373) and NBP607-V (n = 378). The seroconversion rates of NBP607-QIV were 52.4%, 51.2%, 43.7% and 55.8% against A/H1N1, A/H3N2, B/Yamagata and B/Victoria, respectively. Non-inferiority against shared strains and superiority against alternate-lineage B strains were demonstrated for NBP607-QIV vs. NBP607-Y and NBP607-V. A total of 730 reactions occurred in 324 (43.1%) subjects of NBP607-QIV group. Majority of ADRs was solicited (99.2%) and mild (90.3%) in intensity. In adults (aged 19-59 years), solicited local AEs were slightly more frequent in NBP607-QIV group than NBP607-Y or NBP607-V group (40.9%, 33.4% and 32.5%, respectively). One SAE was observed among NBP607-QIV group, which was considered to be unrelated to the study vaccine within 3 weeks of vaccination and no vaccine-related SAEs were reported up to 6 months after vaccination.
NBP607-QIV is a safe, well-tolerated and immunogenic influenza vaccine in Korean adults and elderly subjects.
乙型流感病毒有两个谱系，即山形谱系和维多利亚谱系。这两个谱系在抗原性上不同，很难期望它们之间有交叉保护作用。实际上，流行的乙型流感病毒与疫苗株之间的不匹配情况经常发生。用于生产流感疫苗的细胞培养系统有助于改进疫苗株的选择并扩大疫苗供应。我们研究了细胞培养衍生的四价灭活流感疫苗（NBP607-QIV）在成人和老年受试者中的免疫原性和安全性。
在韩国的10所大学医院进行了一项随机对照III期试验（临床试验编号-NCT02467842）。成人（19至59岁）和老年受试者（≥60岁）以2:1:1的比例随机分配至NBP607-QIV组，以及基于细胞培养的三价灭活流感疫苗-山形谱系（NBP607-Y）组和基于细胞培养的三价灭活流感疫苗-维多利亚谱系（NBP607-V）组。在接种疫苗3周后通过血凝抑制试验评估免疫原性。在接种疫苗后6个月评估安全性：记录7天内的主动报告不良事件（AE）、21天内的非主动报告AE以及6个月内的严重不良事件（SAE）。根据因果关系将AE分类为药物不良反应（ADR）。
共有1503名参与者被随机分配至NBP607-QIV组（n = 7,52）、NBP6,07-Y组（n = 373）和NBP607-V组（n = 378）。NBP607-QIV针对A/H1N1、A/H3N2、B/山形和B/维多利亚的血清转化率分别为52.4%、51.2%、43.7%和55.8%。与NBP607-Y和NBP607-V相比，NBP607-QIV在共享毒株方面显示出非劣效性，在替代谱系B毒株方面显示出优越性。NBP607-QIV组的324名（43.1%）受试者共发生730次反应。大多数ADR是主动报告的（99.2%），且强度为轻度（90.3%）。在成人（19至59岁）中，NBP607-QIV组的主动报告局部AE略比NBP607-Y组或NBP607-V组更频繁（分别为40.9%、33.4%和32.5%）。在NBP607-QIV组中观察到1例SAE，在接种疫苗3周内被认为与研究疫苗无关，且在接种疫苗后6个月内未报告与疫苗相关的SAE。
NBP607-QIV在韩国成人和老年受试者中是一种安全、耐受性良好且具有免疫原性的流感疫苗。
