An epitope-specific chemically defined nanoparticle vaccine for respiratory syncytial virus

Abstract

Respiratory syncytial virus (RSV) can cause severe respiratory disease in humans, particularly in infants and the elderly. However, attempts to develop a safe and effective vaccine have so far been unsuccessful. Atomic-level structures of epitopes targeted by RSV-neutralizing antibodies are now known, including that bound by Motavizumab and its clinically used progenitor Palivizumab. We developed a chemically defined approach to RSV vaccine design, that allows control of both immunogenicity and safety features of the vaccine. Structure-guided antigen design and a synthetic nanoparticle delivery platform led to a vaccine candidate that elicits high titers of palivizumab-like, epitope-specific neutralizing antibodies. The vaccine protects preclinical animal models from RSV infection and lung pathology typical of vaccine-derived disease enhancement. The results suggest that the development of a safe and effective synthetic epitope-specific RSV vaccine may be feasible by combining this conformationally stabilized peptide and synthetic nanoparticle delivery system.

Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape

“…The vaccine platform uses conformationally constrained synthetic peptides conjugated to a synthetic nanoparticle made from self-assembling lipopeptides containing a T-helper epitope and toll-like receptor ligand. 83 The vaccine candidate aims to boost pre-existing immunity in pregnant women or older adults. 84 A phase 1 trial is being done in healthy women.…”

Development of a Platform for Producing Recombinant Protein Components of Epitope Vaccines for the Prevention of COVID-19

“…Conformation of the epitopes can be additionally stabilized by replacing amino acid residues that do not interact with antibodies and the receptor with cysteine residues, which will ensure proximity of their protein chains via formation of disulfide bonds. This approach was implemented in the work by Zuniga et al [ 12 ] during development of the epitope vaccine based on short protein fragments of the respiratory syncytial virus (RSV) conjugated with synthetic nanoparticles.…”

Predicting epitopes for vaccine development using bioinformatics tools

“…Structural epitope mapping could be conducted using X-ray crystallography, nuclear magnetic resonance (NMR), 50 EM, 51 or cryoelectron microscopy (CM). 52 , 53 X-ray crystallography is believed to be the most precise method for structural epitope mapping.…”