Belova E V, Dubileĭ S A, Kravchenko T B, Kolesnikov A V, Zakharova M Iu, Shemiakin I G
Mol Gen Mikrobiol Virusol. 2004(3):21-6.
Anthrax belongs to highly dangerous infections of man and animals. No effective treatment methods for pulmonary types of the disease have been yet developed. The existing anthrax vaccines were designed decades ago and need improvement to fit the large-scale vaccination of population. At the same time, the immunological properties of the anthrax vaccine main component, i.e. of the protective agent, have been poorly studied. We obtained, within the present case study, a panel of mouse monoclonal antibodies to the protective agent and investigated the properties of the highest-affine panel representatives. An unusual phenomenon was detected, which is related with enhancement of the anthrax toxin action on the mouse macrophage-like cell-line in presence of the 1F2 monoclonal antibody. The remaining analyzed antibodies, i.e. 6G8 and 6G7, were found to neutralize effectively the toxin action. The enhancing and neutralizing antibodies were proven to be specific to different domains of the protective antigen and to recognize epitopes in its composition. The antibody-mediated enhancement of the anthrax lethal action is a convincing argument for further development of a new-generation anthrax vaccine. Definition of the linear antigen determinants for neutralizing antibodies in the protective antigens is an important step in the development of the next-generation anthrax vaccine.
炭疽是人和动物的高度危险感染病。目前尚未开发出针对该疾病肺型的有效治疗方法。现有的炭疽疫苗是几十年前设计的,需要改进以适应大规模人群接种。同时,炭疽疫苗主要成分即保护剂的免疫特性研究不足。在本案例研究中,我们获得了一组针对保护剂的小鼠单克隆抗体,并研究了亲和力最高的一组抗体代表的特性。检测到一种不寻常的现象,即1F2单克隆抗体存在时,炭疽毒素对小鼠巨噬细胞样细胞系的作用增强。其余分析的抗体,即6G8和6G7,被发现能有效中和毒素作用。增强抗体和中和抗体被证明对保护抗原的不同结构域具有特异性,并识别其组成中的表位。抗体介导的炭疽致死作用增强是进一步开发新一代炭疽疫苗的有力论据。确定保护抗原中中和抗体的线性抗原决定簇是开发下一代炭疽疫苗的重要一步。