Search bioRxiv⌕ Search

Biology subjects

Hen, J. J.

Publications and source records attributed to Hen, J. J..

2 recordsLinked to original sources

Cloning, expression and characterisation of antigen-specific recombinant bat immunoglobulin from the black flying fox (Pteropus alecto)

Bats are natural reservoirs of viruses that cause severe disease in livestock and humans. Recent high-profile spillover events have directed significant attention towards the interplay between zoonotic viruses and antiviral immunity inherent to bats. Studies have highlighted that bats could harbour some deadly viruses without exhibiting outward symptoms. Various hypotheses have been proposed on how bats coexist with viruses; this includes dampened inflammation and altered innate immunity. However, there is limited literature on the humoral immune response in bats due to the scarcity of bat-specific reagents. To address this knowledge gap, we employed recombinant antibody design techniques to generate antigen-specific recombinant bat antibodies. This strategy involves combining the paratope of well-characterised antiviral antibodies with the IgG1 constant region of the black flying fox (Pteropus alecto). Characterisation of recombinant bat antibodies have revealed that they display canonical features of mammalian IgG. Additionally, recombinant bat antibodies display a binding and neutralising profile akin to human antibody counterparts. This approach provides much needed diagnostic tools and novel reagents to accelerate research into bat antibody immunity.

immunology↗

A protective bispecific antibody targets both Nipah virus surface glycoproteins and limits viral escape

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion (F) nanobody with an anti-receptor binding protein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within prefusion F of NiV and HeV, and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP mAb m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants.

microbiology↗