The entire nucleotide sequence of the G gene of three human respiratory syncytial virus (HRSV) isolates (antigenic group B) has been determined. These three viruses (named BA viruses) were isolated in Buenos Aires in 1999 from specimens collected in different hospitals and at different dates. BA viruses have an exact duplication of 60 nucleotides in the G gene, starting after residue 791. This duplication is flanked by a repeat of four nucleotides (GUGU) and can fold into a relatively stable secondary structure. These features suggest a possible mechanism for the generation of a duplicated G segment. The predicted polypeptide is lengthened by 20 amino acids (residues 260-279) and this is reflected in the slower electrophoretic mobility of the G protein precursor of BA viruses compared with related viruses. The changes reported here expand the examples of drastic genetic alterations that can be introduced into the G protein sequence of HRSV while it replicates in its natural host.

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.

Respiratory syncytial virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanized monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F protein with subnanomolar affinity. ALX-0171 demonstrated in vitro neutralization superior to that of palivizumab against prototypic RSV subtype A and B strains. Moreover, ALX-0171 completely blocked replication to below the limit of detection for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses tested at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.