Q: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
The respiratory syncytial virus (RSV) fusion (F) glycoprotein is a major target of neutralizing antibodies arising from natural infection, and antibodies that specifically bind to the prefusion conformation of RSV F generally demonstrate the greatest neutralization potency. Prefusion-stabilized RSV F variants have been engineered as vaccine antigens, but crystal structures of these variants have revealed conformational differences in a key antigenic site located at the apex of the trimer, referred to as antigenic site . Currently, it is unclear if flexibility in this region is an inherent property of prefusion RSV F or if it is related to inadequate stabilization of site in the engineered variants. Therefore, we set out to investigate the conformational flexibility of antigenic site , as well as the ability of the human immune system to recognize alternative conformations of this site, by determining crystal structures of prefusion RSV F bound to neutralizing human-derived antibodies AM22 and RSD5. Both antibodies bound with high affinity and were specific for the prefusion conformation of RSV F. Crystal structures of the complexes revealed that the antibodies recognized distinct conformations of antigenic site , each diverging at a conserved proline residue located in the middle of an -helix. These data suggest that antigenic site exists as an ensemble of conformations, with individual antibodies recognizing discrete states. Collectively, these results have implications for the refolding of pneumovirus and paramyxovirus fusion proteins and should inform development of prefusion-stabilized RSV F vaccine candidates. Respiratory syncytial virus (RSV) is a pervasive pathogen that causes severe lower respiratory tract infections, leading to~100,000 deaths globally each year and hundreds of millions of dollars in healthcare costs. However, despite its prevalence, there is no vaccine for RSV and the only available therapy is limited to high-risk infants, leaving the vast majority of people with no effective means of prevention or treatment. The RSV fusion (F) protein is a major target of neutralizing antibodies, including extremely potent antibodies that PLOS Pathogens | https://doi.recognize prefusion-specific epitopes. In this study, we determined the crystal structures of two neutralizing human antibodies bound to prefusion RSV F. Our results reveal that each antibody recognizes a different conformation of a neutralization-sensitive epitope, suggesting that this region is inherently flexible and may be important for RSV F function. These results should guide future vaccine-design efforts and help elucidate the mechanisms of RSV F triggering and fusion. Conformational flexibility of antigenic site PLOS Pathogens | https://doi.
A:
Alternative conformations of a major antigenic site on RSV F