Zuniga Armando, Rassek Oliver, Vrohlings Melissa, Marrero-Nodarse Aniebrys, Moehle Kerstin, Robinson John A, Ghasparian Arin
Virometix AG, Schlieren, Switzerland.
Shape Biopharmaceuticals Inc, Cambridge, MA, USA.
NPJ Vaccines. 2021 Jun 18;6(1):85. doi: 10.1038/s41541-021-00347-y.
Respiratory syncytial virus (RSV) can cause severe respiratory disease in humans, particularly in infants and the elderly. However, attempts to develop a safe and effective vaccine have so far been unsuccessful. Atomic-level structures of epitopes targeted by RSV-neutralizing antibodies are now known, including that bound by Motavizumab and its clinically used progenitor Palivizumab. We developed a chemically defined approach to RSV vaccine design, that allows control of both immunogenicity and safety features of the vaccine. Structure-guided antigen design and a synthetic nanoparticle delivery platform led to a vaccine candidate that elicits high titers of palivizumab-like, epitope-specific neutralizing antibodies. The vaccine protects preclinical animal models from RSV infection and lung pathology typical of vaccine-derived disease enhancement. The results suggest that the development of a safe and effective synthetic epitope-specific RSV vaccine may be feasible by combining this conformationally stabilized peptide and synthetic nanoparticle delivery system.
呼吸道合胞病毒（RSV）可导致人类严重的呼吸道疾病，尤其是在婴儿和老年人中。然而，迄今为止，研发一种安全有效的疫苗的尝试均未成功。目前已知RSV中和抗体靶向的表位的原子水平结构，包括与莫他维珠单抗及其临床使用的前身帕利珠单抗结合的表位。我们开发了一种化学定义的RSV疫苗设计方法，该方法能够控制疫苗的免疫原性和安全性特征。结构导向的抗原设计和合成纳米颗粒递送平台产生了一种候选疫苗，该疫苗可引发高滴度的帕利珠单抗样、表位特异性中和抗体。该疫苗可保护临床前动物模型免受RSV感染以及疫苗衍生疾病增强典型的肺部病理影响。结果表明，通过将这种构象稳定的肽与合成纳米颗粒递送系统相结合，开发一种安全有效的合成表位特异性RSV疫苗可能是可行的。
