Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention

TLDR

Human respiratory syncytial virus is the leading cause of pediatric respiratory infections worldwide, and the only specific treatment is the monoclonal antibody Palivizumab, which targets an epitope common to both prefusion and postfusion conformations of the F glycoprotein. The study reports a novel class of antibodies that selectively bind the prefusion form of the F protein and account for the majority of neutralizing activity in rabbit serum and the human Ig preparation Respigam. These prefusion‑specific antibodies provide new avenues for immune intervention against hRSV and warrant evaluation in vaccine trials.

Abstract

Human respiratory syncytial virus (hRSV) is the most important viral agent of pediatric respiratory infections worldwide. The only specific treatment available today is a humanized monoclonal antibody (Palivizumab) directed against the F glycoprotein, administered prophylactically to children at very high risk of severe hRSV infections. Palivizumab, as most anti-F antibodies so far described, recognizes an epitope that is shared by the two conformations in which hRSV_F can fold, the metastable prefusion form and the highly stable postfusion conformation. We now describe a unique class of antibodies specific for the prefusion form of this protein that account for most of the neutralizing activity of either a rabbit serum raised against a vaccinia virus recombinant expressing hRSV_F or a human Ig preparation (Respigam), which was used for prophylaxis before Palivizumab. These antibodies therefore offer unique possibilities for immune intervention against hRSV, and their production should be assessed in trials of hRSV vaccines.