Isolation and characterisation of #Nipah virus neutralising candidate therapeutic monoclonal #antibodies from an #mRNA-immunised pig

 

Abstract

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus with epidemic potential. Despite the threat NiV poses, no therapeutics are licensed to treat infection. Studies have shown that monoclonal antibodies (mAb) can protect animals against NiV and the related Hendra virus (HeV). The best studied mAb, m102.4, has been used to treat infected patients on a compassionate basis, and has entered clinical trials. However, there is a need to define additional mAbs with therapeutic potential, which could be combined with m102.4 to improve neutralising potency and breadth. Here, we isolated five high affinity mAbs from an mRNA immunised pig, which bound the G glycoprotein derived from NiV Malaysia strain (NiV-M), and one of which (mAb A2) also bound HeV G. Aligned with this, all mAbs neutralised NiV-M pseudovirus but only mAb A2 neutralised pseudovirus representing the NiV Bangladesh (NiV-B) strain. mAb A2 and the most potent NiV-M neutralising mAb, C1, showed minimal competition with each other and m102.4, suggesting recognition of non-overlapping epitopes. Single-particle cryogenic electron microscopy of the NiV-M G receptor binding domain complexed to A1 and C2 Fab fragments revealed distinct epitopes that did not overlap with the receptor-binding site, targeted by m102.4, suggesting action through steric impedance of receptor binding or interference downstream of receptor engagement. Inoculation of mAb A2 to hamsters did not provide complete protection against NiV-B challenge (60% survival), however, a split dose of mAb A2 and m102.4 provided the same protection as m102.4 alone (100% survival). Collectively, these data demonstrate the potential of the porcine model for isolation of therapeutic candidate mAbs, which contribute both to our understanding of the NiV G antigenic landscape, and the development of mAb combinations, that exert complementary mechanisms of neutralisation, for therapeutic intervention.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

European Commission, https://ror.org/00k4n6c32, VetBioNet, EMJMD LIVE

Innovate UK, 971555

UK Research and Innovation, BBS/E/I/00007031, BBS/E/I/00007037, BBS/E/I/00007038, BBS/E/I/00007039, MR/S007555/1, BB/T008784/1

Wellcome Trust, 203141/Z/16/Z

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.28.745669v1?rss=1

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Mechanistic and #antigenic boundaries of #Henipavirus and Parahenipavirus #glycoproteins

 

Abstract

Henipaviruses, in the Paramyxoviridae family, includes the highly virulent Nipah virus that causes reoccurring outbreaks of deadly disease. Recent discoveries of Henipavirus-like species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized and prompted the reorganization of these viruses into the Henipavirus and Parahenipavirus genera. Here, to explore the limits of structural and antigenic variation in both genera, collectively referred to as HNVs, we construct an expanded, diverse panel of HNV fusion and attachment glycoproteins from non-redundant HNV strains that better reflect global HNV diversity. We express and purify the fusion protein ectodomains and the attachment protein head domains and study their biochemical and biophysical properties. We perform immunization experiments in mice, eliciting antibodies reactive to multiple HNV fusion proteins. Cryo-electron microscopy structures elucidate molecular determinants of differential pre-fusion state stability and higher order contacts. A crystal structure of the Gamak virus attachment head domain reveals an additional domain appended to the conserved 6-bladed, β-propeller fold. Taken together, these studies expand the known structural and antigenic limits of the HNVs, reveal cross-reactive epitopes within both genera and provide foundational data for the development of broadly reactive countermeasures.

Source: 

Link: https://www.nature.com/articles/s41467-026-74212-8

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Three decades of #discovery: An overview of #Hendra virus, the original #Henipavirus

 

Abstract

Hendra virus (HeV) emerged in Australia in 1994, causing a devastating outbreak among horses in Brisbane with spread to humans, resulting in one death. This nonsegmented, negative-stranded RNA virus belongs to the family Paramyxoviridae and represents the first zoonotic paramyxovirus isolated from bats. Flying foxes (genus Pteropus) serve as the natural reservoir, with all four mainland Australian species carrying antibodies with no apparent disease. HeV initiates infection by binding ephrin-B2 receptors on vascular endothelial cells, driving characteristic pathology involving vasculitis, thrombosis, and neurological complications. Horses are amplifying hosts, shedding virus abundantly in respiratory secretions and posing transmission risks to humans during invasive procedures. To date, seven confirmed human infections have been documented, with a 57% fatality rate, presenting as severe respiratory disease or progressive encephalitis. Two genetic variants are now recognized: the original HeV genotype 1 and the emerging HeV genotype 2, identified in limited equine cases. Recent surveillance of bat roosts revealed substantial viral diversity, with peak shedding occurring during winter—coinciding with equine spillover peaks. Prevention integrates multiple strategies: the licensed equine vaccine Equivac which provides One Health protection for both horses and human contacts; biosecurity measures including proper PPE; and habitat restoration to reduce nutritional stress in bat populations. Emerging therapeutics include monoclonal antibodies, with m102.4 showing cross-protective activity against both HeV and the closely related Nipah virus. No licensed human vaccines currently exist, though candidates are in development. Future prevention strategies increasingly recognize the importance of Indigenous-led conservation approaches alongside biomedical interventions. This review will focus on the history of HeV, virus replication and diversity, epidemiology, clinical manifestations, diagnosis, treatment, prevention, as well as ecological and interdisciplinary countermeasures.

Author summary

Hendra virus (HeV) was first detected in 1994, with two outbreaks occurring within 2 months of that year. One was the index outbreak in the Brisbane suburb of Hendra, and the other was retrospectively diagnosed in the following year. This review examines the discoveries that have been made in the 30 years since its discovery.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014138

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#Nipah virus molecular #detection from whole #blood and respiratory #swabs in a rapid field-ready protocol

 

Highlights

• A Nipah virus real-time RT-PCR was developed for this study and display dynamic amplification, with sensitive (limit of detection 3.7-4.2 copies/µL) and specific detection.

• The assay was adapted for use on a portable, battery-powered real-time thermocycler.

• When paired with instrument-free RNA extraction, Nipah virus RNA was rapidly detected from contrived whole blood and nasopharyngeal swabs without electricity.

• The combined of Extract & Store and the Palm PCR S1e device offers a viable solution for field-based molecular detection of Nipah virus.

Abstract

Background

Nipah virus (NiV) is a highly pathogenic, zoonotic paramyxovirus with significant public health implications due to high associated mortality and potential for human-to-human transmission. Current diagnostic testing options for NiV are limited and require extensive laboratory infrastructure.

Objective

Develop a field-deployable testing workflow for timely NiV detection.

Study design

A NiV real-time RT-PCR (rRT-PCR) was designed for a highly conserved region of the nucleocapsid gene and tested with RNA from Bangladesh and Malaysia NiV strains. The NiV rRT-PCR was evaluated on Rotor-Gene Q and Palm PCR S1e thermocyclers following instrument free RNA extraction (Extract & Store).

Results

Initial analytical evaluation, on a Rotor-Gene Q, demonstrated dynamic amplification and a limit of detection (LoD) of 3.7-4.2 copies/µL without amplification of related paramyxoviruses. The assay was adapted for the portable, battery-powered, self-contained Palm PCR S1e thermocycler, and exhibited linear detection with a LoD of 30.7 copies/µL. RNA extraction from contrived whole blood and pharyngeal swabs using the Extract & Store workflow yielded comparable results to automated extraction on a KingFisher Apex instrument. The entire assay, including extracted and stabilized RNA controls from BSL-1 strains, was successfully transferred to Aga Khan University with ambient temperature shipping and yielded similar performance.

Conclusions

The combination of Extract & Store and the Palm PCR S1e device offers a viable solution for field-based molecular detection of NiV. While limitations were noted for reaction setup on the Palm PCR, this presents a flexible and accessible workflow for rapid, portable detection of high-consequence pathogens in resource-constrained settings.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S138665322600020X?dgcid=rss_sd_all

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Functional and #antigenic constraints on the #Nipah virus #fusion protein

 

Abstract

Nipah virus is a highly pathogenic virus in the family Paramyxoviridae that utilizes two distinct surface glycoproteins to infect cells. The receptor-binding protein (RBP) binds host receptors whereas the fusion protein (F) merges viral and host membranes. Here, we use nonreplicative pseudoviruses to safely measure the effects of all F single amino acid residue mutations on its cell entry function and neutralization by monoclonal antibodies. We compare mutational tolerance in F with previous experimental measurements for RBP and show that F is much more functionally constrained than the RBP. We also identify mutationally intolerant sites on the F trimer surface and core that are critical for proper function, and describe mutations that are candidates for stabilizing F in the prefusion conformation for vaccine design. We quantify how F mutations affect neutralization by six monoclonal antibodies, and show that the magnitude of mutational effects on neutralization varies among antibodies. Our measurements of mutational effects on Nipah virus F predict the ability of the antibodies to neutralize the related Hendra virus. Overall, our work defines the functional and antigenic constraints on the F protein from an important zoonotic virus.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2529505123?af=R

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The intracellular #virus-host #interface of #henipaviruses

ABSTRACT

The Henipavirus genus comprises five viral species, of which the prototype members, Hendra virus (HeV) and Nipah virus (NiV), are reported to infect humans. In humans and other spill-over hosts, HeV/NiV can cause severe respiratory and/or encephalitic disease, with mortality rates exceeding 50%; currently, there are no approved human vaccines and only limited therapeutic options. As members of the family Paramyxoviridae, henipaviruses have six “core” structural proteins and typically three additional accessory proteins that are expressed from the P gene. Several of these proteins are multifunctional, with roles in forming intracellular interfaces with the host (in particular, M, P, V, W, and C proteins), to modulate processes including antiviral responses, supporting viral replication. Understanding the molecular basis of these interfaces and their functions is critical to delineate the mechanisms of pathogenesis and may inform new strategies to combat infection and disease. Recent research has significantly advanced the understanding of the functions and interactions of multifunctional intracellular henipavirus proteins, including revealing novel roles in subverting the nucleolar DNA damage response (DDR) and modulating the functions of 14-3-3 proteins. This review will discuss the intracellular virus-host interface, focusing on the M, P, V, W, and C proteins of HeV/NiV, with a focus on recently identified functions and interactions.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00770-25?af=R

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#Henipavirus in Northern Short-Tailed #Shrew, #Alabama, #USA

{Excerpt}

To the Editor: The article “Henipavirus in northern short-tailed shrew, Alabama, USA,” (1), describing the discovery of Camp Hill virus (family Paramyxoviridae) in the northern short-tailed shrew (Blarina brevicauda), sparked major media attention and raised concerns about zoonotic transmission and potential pandemic risk. However, it would be advisable to reevaluate this virus discovery within the broader context of related viruses. The increase in identified henipa-like viruses in various shrew species (2–4) led the International Committee on Taxonomy of Viruses to classify these henipa-like viruses into a distinct genus, Parahenipavirus (5), acknowledging their genetic difference from the highly pathogenic Hendra and Nipah virus.

(...)

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0401_article

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Co-Infections with #Orthomarburgviruses, #Paramyxoviruses, and #Orthonairoviruses in Egyptian Rousette #Bats, #Uganda and Sierra Leone

Abstract

We report 1.3% (19/1,511) of Egyptian rousette bats (ERBs) in Uganda and Sierra Leone were co-infected with different combinations of Marburg, Sosuga, Kasokero, or Yogue viruses. To prevent infection by those viruses, we recommend avoiding ERB-populated areas, avoiding ERBs and ERB-contaminated objects, and thoroughly washing harvested fruits before consumption.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1669_article

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