Abstract
Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections in infants and the elderly. Previously, most RSV vaccine antigen design strategies have focused on the stability of the prefusion (PreF) protein trimer conformation. We hypothesized that the RSV monomer might serve as a vaccine candidate immunogen. Here, we constructed an immunofocusing-based RSV F protein Q74 truncated monomer by truncating the RSV F protein and retaining only the head and neck regions. The structural prediction and protein antigenicity characterization of Q74 truncated monomer both indicated that it could bind to the antigenic site Ø-specific antibody D25, suggesting that this immunogen retained the structural features of PreF. In addition, the Q74 truncated monomer not only induced neutralizing and binding antibodies with a strength comparable to that of DS-Cav1 but also focused the immune response on antigenic site Ø and site II. In summary, we found that the RSV F protein monomer designed based on immunofocusing could induce relative immunogenicity and immune protection, providing a design strategy for RSV vaccines.
Keywords:
PreF; antigen design; head region; immunofocusing; monomer; neck region; prefusion; respiratory syncytial virus; structure; vaccine.