Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA; Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.
Trends Immunol. 2021 Mar;42(3):186-197. doi: 10.1016/j.it.2021.01.001. Epub 2021 Jan 26.
'Reverse vaccinology 2.0' aims to rationally reproduce template antibody responses, such as broadly neutralizing antibodies against human immunodeficiency virus-1. While observations of antibody convergence across individuals support the assumption that responses may be replicated, the diversity of humoral immunity and the process of antibody selection are rooted in stochasticity. Drawing from experience with in vitro antibody engineering by directed evolution, we consider how antibody selection may be driven, as in germline-targeting vaccine approaches to elicit broadly neutralizing antibodies and illustrate the potential consequences of over-defining a template antibody response. We posit that the prospective definition of template antibody responses and the odds of replicating them must be considered within the randomness of humoral immunity.
“反向疫苗学 2.0”旨在合理复制模板抗体反应，例如针对人类免疫缺陷病毒-1 的广泛中和抗体。虽然个体之间的抗体趋同观察支持可以复制反应的假设，但体液免疫的多样性和抗体选择的过程都源于随机性。借鉴体外抗体定向进化工程的经验，我们考虑抗体选择可能受到哪些因素的驱动，例如针对种系的疫苗方法来诱导广泛中和抗体，并说明过度定义模板抗体反应的潜在后果。我们假设，在体液免疫的随机性范围内，必须考虑到模板抗体反应的前瞻性定义及其复制的可能性。
