Biology subjects

Bermudez-Mendez, E.

Publications and source records attributed to Bermudez-Mendez, E..

3 recordsLinked to original sources

bioRxiv2026

Structural and functional characterization of polyclonal antibody responses reveals shared and distinct antigenic features of RSV and hMPV fusion proteins

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), members of the Pneumoviridae family, circulate widely and are leading causes of hospitalization for acute respiratory infections in infants and older adults. The viral fusion (F) protein in its prefusion (preF) conformation is the primary target of neutralizing antibodies, yet how naturally elicited circulating polyclonal antibodies are distributed across its antigenic landscape remains poorly understood. Here, we combined serological profiling, site-specific antibody competition assays and electron microscopy-based polyclonal epitope mapping (EMPEM) to characterize preF-directed immunity to RSV and hMPV in healthy adults. All donors exhibited detectable preF-binding antibodies that positively correlated with virus neutralization and broadly recognized multiple antigenic sites, consistent with immunodominance patterns predicted by a surface-centric computational model. Despite this overall similarity, the distribution of responses across individual antigenic sites differed between RSV and hMPV. EMPEM analyses revealed consistent targeting of the highly neutralization-sensitive preF apex (site O) in both viruses, alongside less abundant responses against equatorial and upper-middle epitopes (sites II, III, IV and V). We additionally observed antibody-bound destabilized preF, supporting a model in which antibody binding promotes transient opening of the preF trimer and may interfere with the conformational rearrangements required for membrane fusion. Together, these findings highlight apex-directed antibodies as a prominent feature of naturally acquired pneumovirus immunity in adults and reveal both shared and distinct patterns of antigenic recognition that may inform next-generation vaccine design and antibody-based prophylactics.

immunology↗

bioRxiv2026

Distinct mechanisms of neutralization by antibodies targeting a conserved pneumovirus F epitope

Pneumoviruses cause seasonal outbreaks leading to hospitalizations of vulnerable populations such as infants and the elderly. Cross-neutralizing antibodies targeting viral fusion have been isolated from infected individuals, but their elicitation and mechanisms of action remain understudied. Here, we describe two vaccine-elicited antibody classes, LOR24 and LOR69, that bind an overlapping epitope, and identify the somatic mutations that endow their breadth and potency, respectively. Cryo-electron microscopy structures of both antibodies bound to the HRSV fusion (F) protein show binding modes distinct from each other and from the previously described cross-neutralizing antibody MPE8, yet they all use similar motifs for binding. Complementary in vitro and electron microscopy experiments show that these antibodies either lock prefusion F as a trimer, arrest F in a monomeric or intermediate state, or promote the transition to the postfusion conformation. This work sheds light on mechanisms of pneumovirus neutralization and the elicitation of cross-neutralizing antibody responses.

immunology↗

bioRxiv2022

Incomplete bunyavirus particles contribute to within-host spread and between-host transmission

Bunyaviruses lack a specific mechanism to ensure the incorporation of a complete set of genome segments into each virion, explaining the generation of incomplete virus particles lacking one or more genome segments. Such incomplete virus particles, which may represent the majority of particles produced, are generally considered to interfere with virus infection and spread. Using the three-segmented Rift Valley fever virus as a model bunyavirus, we here show that two distinct incomplete virus particle populations that are unable to spread autonomously, are able to efficiently complement each other in both mammalian and insect cells following co-infection. We further show that incomplete virus particles are capable of co-infecting mosquitoes, resulting in the rescue of infectious virus that is able to disseminate to the mosquito salivary glands. Our findings reveal a significant role of incomplete particles in within-host spread and between-host transmission, reminiscent of the life cycle of multipartite viruses.

microbiology↗