Explore the vast range of titles available.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children. To date, no vaccine is approved for the broad population of healthy infants. MEDI8897, a potent anti-RSV fusion antibody with extended serum half-life, is currently under clinical investigation as a potential passive RSV vaccine for all infants. As a ribonucleic acid virus, RSV is prone to mutation, and the possibility of viral escape from MEDI8897 neutralization is a potential concern. We generated RSV monoclonal antibody (mAb)-resistant mutants (MARMs) in vitro and studied the effect of the amino acid substitutions identified on binding and viral neutralization susceptibility to MEDI8897. The impact of resistance-associated mutations on in vitro growth kinetics and the prevalence of these mutations in currently circulating strains of RSV in the United States was assessed. Critical residues identified in MARMs for MEDI8897 neutralization were located in the MEDI8897 binding site defined by crystallographic analysis. Substitutions in these residues affected the binding of mAb to virus, without significant impact on viral replication in vitro. The frequency of natural resistance-associated polymorphisms was low. Results from this study provide insights into the mechanism of MEDI8897 escape and the complexity of monitoring for emergence of resistance.

The COVID-19 pandemic spurred mRNA vaccine innovation, but new SARS-CoV-2 variants highlight the need for vaccines with improved potency and durability. This report presents a novel mRNA vaccine platform encoding virus-like particle antigens (mRNA-VLPs) that mimic native virus structures, aiming to boost antibody responses via enhanced B cell activation. In animal studies, mRNA-VLP vaccines generated stronger neutralizing antibody responses across multiple variants compared to conventional mRNA vaccines expressing native spike proteins. In non-human primates, these elevated antibodies lasted at least six months. An mRNA-VLP vaccine encoding the Omicron spike outperformed traditional mRNA vaccines in mice as both a monovalent and bivalent (with ancestral spike) formulation. In hamsters, even low doses of mRNA-VLP vaccine provided complete protection, similar to high doses of native spike mRNA vaccines. These results suggest the mRNA-VLP platform could significantly strengthen vaccine efficacy and breadth against evolving SARS-CoV-2 variants.