Biology subjects

Esfahani, B. G.

Publications and source records attributed to Esfahani, B. G..

4 recordsLinked to original sources

bioRxiv2026

A pan-serotype human monoclonal antibody protects against pneumococcal infection by targeting multiple choline binding domain proteins

Streptococcus pneumoniae remains a global health threat, particularly to young children, the elderly, and immunocompromised individuals. Pneumococcal vaccines targeting the bacterial capsule polysaccharide do not protect against all 100+ pneumococcal serotypes, contributing to non-vaccine serotype infections and antibiotic resistance. To address these limitations, we isolated human monoclonal antibodies (mAbs) targeting pneumococcal surface proteins and identified a first-in-class mAb, derived from a patient with prior pneumococcal infection, namely mAb 5995-40. mAb 5995-40 bound multiple pneumococcal proteins, including PcpA and PspA, through a conserved choline-binding domain shared across serotypes. Functionally, mAb 5995-40 provided complete protection in lethal pneumococcal challenge models and improved survival in influenza A, influenza B, and respiratory syncytial virus-associated bacterial coinfection models. Mechanistic studies showed enhanced opsonophagocytic killing, reduced bacterial dissemination, and blocked epithelial translocation. Cryo-electron microscopy identified a repeating motif within the choline-binding domain targeted by mAb 5995-40, highlighting its potential as a broadly protective pneumococcal therapeutic.

immunology↗

bioRxiv2026

Molecular basis for protection and cross-protection by human antibodies targeting the parainfluenza virus hemagglutinin-neuraminidase protein

Human parainfluenza viruses (PIVs) are a leading cause of respiratory illness, particularly in vulnerable populations where infection can lead to severe disease. Despite their clinical impact, there are currently no licensed vaccines or effective antiviral treatments available. PIVs have two large surface proteins, the fusion and hemagglutinin-neuraminidase (HN) proteins, both of which are targets of neutralizing antibodies. In this study, we identified and characterized two human monoclonal antibodies (mAbs), 5217-2 and 5217-9, which bind recombinant PIV3 HN protein, bind PIV3-infected cells, and are neutralizing in vitro. We determined the binding epitopes of the PIV3 HN-specific mAbs via biolayer interferometry and found mAb 5217-9 targets a previously defined neutralizing epitope while mAb 5217-2 binds a unique epitope, enabling a more complete understanding of the antigenic landscape. To further understand the newly defined epitope, we determined a cryo-electron microscopy (cryo-EM) structure of mAb 5217-2, which revealed an epitope adjacent to the PIV3 HN protein active site. We also determined the structure of the previously discovered anti-PIV3 HN mAb PIV3HN-09, which was previously shown to be partially protective in vivo. In a hamster challenge model of PIV3, mAb 5217-2 was determined to significantly reduce lung viral titers, demonstrating its protective capacity. Furthermore, as the site 2-directed mAb PIV3HN-05 was previously shown to cross-neutralize PIV1, we evaluated its protective efficacy in an animal challenge model with PIV1, which demonstrated a reduction in lung viral titers. Overall, these findings provide new insights into the antigenic epitopes on the PIV3 HN protein to support structure-based vaccine design efforts and demonstrate new protective mAbs for both PIV3 and PIV1.

immunology↗

bioRxiv2026

Myosin Filaments of Vertebrate Skeletal and Cardiac Muscle are Highly Similar, but not Identical

Striated muscles consist of two filament types, one composed mostly of actin and the other composed mostly of myosin1,2. Actin filaments are highly similar across different muscle types and species both invertebrate and vertebrate3. Myosin filaments of vertebrate striated muscle are quite homogeneous in structure having identical lengths, governed by the giant protein titin4,5, and rotational symmetries while varying mostly in the isoforms of its proteins. Conversely, myosin filaments from invertebrate striated muscle are highly heterogeneous in multiple ways even within a single organism. Myosin filaments from vertebrate cardiac muscle have been shown to be highly similar in structure between mice and humans6-8. Conversely, thick filaments from the highly specialized insect indirect flight muscle have been shown to be highly variable in structure9-14. Here we used the drug mavacamten to stabilize a myosin head conformation known as the interacting heads motif in a fast skeletal muscle of rabbits, a highly studied model system. We show that the structure of relaxed rabbit skeletal muscle thick filaments is highly similar to those of relaxed human and mouse cardiac muscle, differing primarily in the positioning of some domains of myosin binding protein C vis-a-vis titin. In the context of the very different structures from indirect flight muscle, the result highlights different solutions to the same problems, control of muscle force and the requirements of endothermy, the internal generation of heat. In mammals, thick filaments are poised for varying levels of myosin activation15, while indirect flight muscle is poised for narrowly defined, high frequency contraction. In mammals, endothermy is a continuous problem; in insects, endothermy is primarily necessary for flight16.

biophysics↗

bioRxiv2025

Structural Basis for Childhood Antibody Recognition of The Human Metapneumovirus Fusion Protein

Human metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and adults, with the majority of children being seropositive for hMPV by five years of age. Infants, older adults, and immunocompromised individuals are more susceptible to severe hMPV infections that can lead to hospitalization and death. The hMPV fusion (F) protein is the sole target of neutralizing antibodies, and while the most common neutralizing epitopes on the hMPV F protein targeted by B cells in hMPV-infected adults have been previously determined, the antibody response in hMPV-infected children remains undefined. We isolated a panel of human monoclonal antibodies (mAbs) from children previously infected with hMPV (MPV498, MPV499, MPV510, MPV511, and MPV513), and the mAbs were assessed for binding avidity, neutralization potency, epitope specificity, and in vivo efficacy. All mAbs were neutralizing, and epitope binning revealed the presence of four different epitopes targeted by the mAbs. We determined the cryo-EM structures of four mAbs in complex with the hMPV F protein, which revealed epitopes located on the hMPV F trimer surface as well as an intratrimer epitope located completely within the hMPV F trimer interface. Furthermore, we determined the prophylactic efficacy of the mAbs in protection against hMPV challenge in mice. Overall, our data reveal new insights into the immunodominant antigenic epitopes on the hMPV F protein in children and identify new mAb therapies for hMPV F disease prevention.

immunology↗