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

By M. Magro, V. Mas, Keith J. Chappell, M. Vázquez, Olga Cano, Daniel Luque, M. C. Terrón, J. Melero, C. Palomo. 2012

272 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Infectious Diseases

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Barney S. Graham
2. F. Sallusto
3. A. Lanzavecchia
4. D. Veesler
5. M. Kanekiyo

In Infectious Diseases

1. D. Veesler
2. David Baker

Citations in the corpus

• Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “, 2017), together with the observation that most neutralizing activity in human sera is prefusion-specific (Magro et al., 2012), predicted that F protein variants stabilized in the prefusion conformation would yield improved vaccine candidates.”
• Influence of Respiratory Syncytial Virus F Glycoprotein Conformation on Induction of Protective Immune Responses (2016, background): “Recent studies have provided persuasive evidence that protection is afforded mainly by neutralizing antibodies and that most neutralizing antibodies in humans recognize epitopes found exclusively in the prefusion conformation of the hRSV F glycoprotein (34, 35).”
• Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors (2016, unknown): “These findings are consistent with the results obtained from human sera mapping, which determined that the majority of neutralizing activity can be removed by preincubation with preF (4, 8) and that preF-specific sites other than site Ø make up a considerable fraction of preF-specific neutralizing a”
• Prefusion F–specific antibodies determine the magnitude of RSV neutralizing activity in human sera (2015, background): “An earlier study showed that in high-titer pooled human immunoglobulin, NT activity could not be removed with post-F, suggesting that pre-F–specific antibodies may be important in RSV neutralization (17).”