The respiratory syncytial virus (RSV) prefusion F‐protein functional antibody repertoire in adult healthy donors

Andreano, Emanuele; Paciello, Ida; Bardelli, Monia; Tavarini, Silvia; Sammicheli, Chiara; Frigimelica, Elisabetta; Guidotti, Silvia; Torricelli, Giulia; Biancucci, Marco; D’Oro, Ugo; Chandramouli, Sumana; Bottomley, Matthew J.; Rappuoli, Rino; Finco, Oretta; Buricchi, Francesca

doi:10.15252/emmm.202114035

Cited by 20 publications

(18 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preliminary exploratory data revealed that the V-306 study subjects displayed higher titer changes in PCA assays when the pre-fusion F protein conformation of RSV F was used as the capturing antigen (unpublished data), likely reflecting a better accessibility of the relevant epitope on the pre-fusion F protein. This may also reflect the diversity of pre-existing neutralizing and non-neutralizing antibodies [ 29 ], and their capacity to interfere with the binding of anti-FsIIm epitope-specific IgG to the PVZ-binding epitope [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine

Leroux-Roels

Bruhwyler²,

Stergiou³

et al. 2023

Vaccines

View full text Add to dashboard Cite

Background: V-306 is a virus-like particle-based vaccine candidate displaying respiratory syncytial virus (RSV) F site II protein mimetics (FsIIm) as an antigenic epitope. Methods: This was a randomized, placebo-controlled, double-blind, dose-escalating, first-in-human study, conducted in 60 women aged 18–45 years. Twenty subjects per cohort (15 vaccine and five placebo) received two V-306 intramuscular administrations on Days 0 and 56 at 15 µg, 50 µg, or 150 µg. Safety and immunogenicity were assessed after each vaccination and for 1 year in total. Results: V-306 was safe and well tolerated at all dose levels, with no increase in reactogenicity and unsolicited adverse events between the first and second administrations. At 50 µg and 150 µg, V-306 induced an increase in FsIIm-specific immunoglobulin G (IgG) titers, which lasted at least 4 months. This did not translate into an increase in RSV-neutralizing antibody titers, which were already high at baseline. No increase in the anti-F protein-specific IgG titers was observed, which were also high in most subjects at baseline due to past natural infections. Conclusions: V-306 was safe and well-tolerated. Future modifications of the vaccine and assay conditions will likely improve the results of vaccination.

show abstract

Section: Discussionmentioning

confidence: 99%

Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine

Leroux-Roels

Bruhwyler²,

Stergiou³

et al. 2023

Vaccines

View full text Add to dashboard Cite

show abstract

“…The data show that, while three subjects had generated antibodies specific for the pre-fusion form of the F protein, the majority of neutralizing antibodies were directed against the F protein bound to both the pre- and post-fusion forms. However, 78 of the 82 antibodies with dual-binding capacity were bound significantly more strongly to the pre-fusion form, which is found most predominantly on virus particles [ 47 ]. The data from these studies emphasize that the neutralization of virus infectivity in vivo is a potentially complex combination of a spectrum of different antibodies with different neutralizing activities.…”

Section: What Can the Sars-cov-2 Field Learn From The Respiratory Syn...mentioning

confidence: 99%

Understanding the SARS-CoV-2 Virus Neutralizing Antibody Response: Lessons to Be Learned from HIV and Respiratory Syncytial Virus

Dimmock

Easton

2023

Viruses

View full text Add to dashboard Cite

The SARS-CoV-2 pandemic commenced in 2019 and is still ongoing. Neither infection nor vaccination give long-lasting immunity and, here, in an attempt to understand why this might be, we have compared the neutralizing antibody responses to SARS-CoV-2 with those specific for human immunodeficiency virus type 1 (HIV-1) and respiratory syncytial virus (RSV). Currently, most of the antibodies specific for the SARS-CoV-2 S protein map to three broad antigenic sites, all at the distal end of the S trimer (receptor-binding site (RBD), sub-RBD and N-terminal domain), whereas the structurally similar HIV-1 and the RSV F envelope proteins have six antigenic sites. Thus, there may be several antigenic sites on the S trimer that have not yet been identified. The epitope mapping, quantitation and longevity of the SARS-CoV-2 S-protein-specific antibodies produced in response to infection and those elicited by vaccination are now being reported for specific groups of individuals, but much remains to be determined about these aspects of the host–virus interaction. Finally, there is a concern that the SARS-CoV-2 field may be reprising the HIV-1 experience, which, for many years, used a virus for neutralization studies that did not reflect the neutralizability of wild-type HIV-1. For example, the widely used VSV-SARS-CoV-2-S protein pseudotype has 10-fold more S trimers per virion and a different configuration of the trimers compared with the SARS-CoV-2 wild-type virus. Clarity in these areas would help in advancing understanding and aid countermeasures of the SARS-CoV-2 pandemic.

show abstract

“…Multiple antigenic sites have been identified on both RSV F and hMPV F proteins. Among the six known antigenic sites of RSV F, pre-fusion-specific sites Ø and V are targeted by over 60% of neutralizing antibodies in humans ( 26 , 27 ), indicating these sites are vital for immune recognition and antibody neutralization ( 28 ). hMPV F shares three antigenic sites (III, IV, V) with RSV F, as several antibodies have been found to cross-react with RSV and hMPV F at these epitopes ( 29 – 32 ).…”

Section: Introductionmentioning

confidence: 99%

A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein

2022

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to the testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and analysis by negative-stain electron microscopy demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. Mice immunized with RHMS-1 generated neutralizing antibodies to both viruses and were completely protected from RSV or hMPV challenge. Overall, this study demonstrates protection against two viruses with a single antigen and supports testing of RHMS-1 in additional pre-clinical animal models.

show abstract

The respiratory syncytial virus (RSV) prefusion F‐protein functional antibody repertoire in adult healthy donors

Cited by 20 publications

References 54 publications

Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine

Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine

Understanding the SARS-CoV-2 Virus Neutralizing Antibody Response: Lessons to Be Learned from HIV and Respiratory Syncytial Virus

A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein

Contact Info

Product

Resources

About