Cascalho Marilia, Balin Samuel J, Platt Jeffrey L
Department of Microbiology & Immunology and Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Immunotherapy. 2017 Jun;9(8):659-667. doi: 10.2217/imt-2017-0030.
Mutable viruses, such as HIV, pose difficult obstacles to prevention and/or control by vaccination. Mutable viruses rapidly diversify in populations and in individuals, impeding development of effective vaccines. We devised the 'mutable vaccine' to appropriate the properties of mutable viruses that undermine conventional strategies. The vaccine consists of a DNA construct encoding viral antigen and regulatory sequences that upon delivery to B cells target the enzymatic apparatus of 'somatic hypermutation' causing the construct to mutate one million-times baseline rates and allowing production and presentation of antigen variants. We postulate the mutable vaccine might thus anticipate diversification of mutable viruses, allowing direct control or slowing of evolution. Initial work presented here should encourage consideration of this novel approach.
可变病毒，如艾滋病毒，给通过疫苗接种进行预防和/或控制带来了艰巨障碍。可变病毒在群体和个体中迅速多样化，阻碍了有效疫苗的研发。我们设计了“可变疫苗”，以利用那些破坏传统策略的可变病毒的特性。该疫苗由一个编码病毒抗原的DNA构建体和调控序列组成，一旦递送至B细胞，就会靶向“体细胞超突变”的酶促机制，使构建体以比基线速率高一百万倍的速度发生突变，并允许产生和呈递抗原变体。我们推测，可变疫苗可能因此能够预测可变病毒的多样化，从而实现对进化的直接控制或减缓。本文介绍的初步研究工作应能促使人们考虑这种新方法。
