Scientists at the Institute of Advanced Virology (IAV), Thonnakkal, Thiruvananthapuram, have developed a novel way of generating non-infectious Nipah virus-like particles (VLPs) in the laboratory, which mimic the wild type Nipah virus (NiV).
This new method offers an alternate, safe and effective platform for developing neutralising antibodies against NiV in a bio safety level-2 (BSL) laboratory. The IAV team has thus come one step closer to its mandate for developing monoclonal antibodies and anti-virals against NiV and similar pathogens.
Only limited studies now
The zoonotic virus Nipah is a highly pathogenic paramyxovirus, with a fatality rate of up to 80% in affected humans. Yet, research studies, especially virus neutralisation assays to develop specific antivirals or therapeutics against NiV, have been limited because of the extreme level of biosafety precautions required for handling this BSL-4 pathogen.
Virus neutralisation assays are critical for the development and evaluation of vaccines and immunotherapeutics, as well as for conducting basic research into the immune response and pathogenesis of NiV. These tests, which traditionally require to be done in high security labs with the infectious organism, can now be done safely in BSL-2 labs in the country using the NiV-VLPs, Director of IAV E. Sreekumar says.
The laboratory studies by the team of researchers led by Mohanan Valiyaveetil in the Department of General Virology at IAV have been detailed in the manuscript,” Highly sensitive and quantitative HiBiT-tagged Nipah virus-like particles: A platform for rapid antibody neutralisation studies,” which appeared on May 24, 2024 in the international journal Heliyon by Cell Press.
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material.
Particles’ characteristics
VLPs carry most of the characteristics of the virus, except their ability to replicate (because it lacks the viral genome). VLPs have long been recognised as effective quantitative platforms for studying viral binding and entry kinetics of the virus. But the advent of NanoBiT technology and “HiBiT-tagged” VLP (HiBiT is an 11 amino acid peptide ) makes it far more sophisticated.
The genome of the NiV encodes six major proteins: glycoprotein (G), fusion protein (F), matrix (M), nucleocapsid (N), long polymerase (L) and phosphoprotein (P).
In the current study, IAV scientists generated “HiBiT-tagged” Nipah virus-like particles (NiV-VLPs) using plasmid-based expression systems, encoding the NiV structural proteins G, F, and M.
The VLPs thus produced were morphologically and functionally identical to the native virus. The inclusion of a highly sensitive HiBiT tag on these VLPs accelerates their potential in antiviral drug screening and vaccine development.
Reduced risks
The scientists say that the potential risks of using native viruses in virus-host interaction assays, immune response studies, immunoglobulin validations and other virus-based assays could be alleviated with the use of these HiBiT tagged VLPs.
The concept of generating VLPs or tagged VLPs (eg: HiBiT) is applicable to several other virulent pathogens but it is particularly advantageous to apply this methodology to BSL-3/BSL-4 level viruses, to enable studies in lower bio-containment levels.
This study, which is also IAV’s first independent research publication after its inception two years ago, is the first of its kind using HiBiT tagged NiV-VLPs, demonstrating their application in neutralisation assays, the scientists say.
However, extensive and rigorous studies using multiple neutralising antibodies and antivirals that block entry of the virus are needed to conclusively show the efficacy of these VLPs, they added.
