Functional and antigenic landscape of the Nipah virus receptor binding protein

Abstract

Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.

A mRNA Vaccine Encoding for a 60-mer G Glycoprotein Nanoparticle Elicits a Robust Neutralizing Antibodies Response Against the Nipah Virus

“…Interestingly, few of the NiV G mutations in known NiV strains are antibody escape mutations. A recent study using a pseudotyped virus deep mutational screening library of NiV G to map NiV escape mutations for six neutralizing antibodies that target a diversity of epitopes on the NiV G head domain found only one amino-acid mutation in natural Nipah strains (P274S in Bangladesh genotype) 31 . Assuming limited human-to-human transmission and antigenic escape of NiV, and the current evolutionary rate of the NiV G head domain, the mRNA NiV G-NP vaccine could maintain its efficacy over a decade or more.…”