Gwon Yong-Dae, Kim Sehyun, Cho Yeondong, Heo Yoonki, Cho Hansam, Park Kihoon, Lee Hee-Jung, Choi Jiwon, Poo Haryoung, Kim Young Bong
Department of Bio-industrial Technologies, Konkuk University, Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea.
Viral Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
PLoS One. 2016 May 5;11(5):e0154824. doi: 10.1371/journal.pone.0154824. eCollection 2016.
An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)-forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×10(7) FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.
2009年甲型H1N1流感爆发,这是21世纪的首次流感大流行,传播给了超过100万人,并导致18449人死亡。目前许多国家的现状是使用基于细胞或基于鸡蛋的灭活疫苗来制备流感疫苗。然而,传统的流感疫苗平台有几个局限性。为了克服这些局限性,许多研究人员尝试了各种方法来开发替代生产平台。作为替代方法之一,我们报道了使用杆状病毒DNA疫苗(AcHERV-HA)进行流感HA疫苗接种的效果。然而,仅针对HA抗原的AcHERV-HA疫苗引发的免疫反应低于商业灭活疫苗。为了克服这种先前疫苗的局限性,我们构建了一种针对大流行性甲型流感病毒/加利福尼亚/04/2009(pH1N1)的、基于杆状病毒的、形成人内源性逆转录病毒(HERV)包膜的病毒样颗粒(VLP)的DNA疫苗(称为AcHERV-VLP)。用AcHERV-VLP(1×10⁷ FFU AcHERV-VLP,肌肉注射)免疫BALB/c小鼠,并与用灭活疫苗免疫的小鼠或用AcHERV-HA免疫的小鼠进行比较。结果,AcHERV-VLP免疫产生了更强的体液免疫反应,并对H1亚组菌株(PR8)表现出中和活性,引发了中和抗体的产生,脾细胞中干扰素-γ分泌水平较高,在用致死剂量的流感病毒攻击后肺部病毒脱落减少。总之,形成VLP的杆状病毒DNA疫苗可能是一种潜在的疫苗候选物,能够有效地将DNA递送至接种者体内,并且形成VLP的DNA引发的免疫原性比基于鸡蛋的灭活疫苗更强。