Loomis, Rebecca (NIAID)
Stewart-Jones, Guillaume (NIAID)
Mascola, John (NIAID)
Nipah virus is an emerging pathogenic paramyxovirus responsible for sporadic and isolated outbreaks of severe respiratory and neurologic disease in Southern Asia. As a zoonotic virus, disease can manifest in both animals and human with indigenous fruit bats acting as natural reservoirs of the virus. The effects of viral infection vary from acute respiratory distress to fatal encephalitis. There are currently no approved therapeutics or vaccines against the virus, and growing concerns that this highly pathogenic infection has the potential to cause larger epidemics capable of inflicting significant mortality burden.
Like the RSV fusion (F) glycoprotein, the Nipah fusion glycoprotein is a target of neutralizing antibodies that mediate protection against infection. Previous studies of prefusion-stabilized F glycoproteins from pneumoviruses and other paramyxoviruses (e.g. RSV and PIVs) have shown they elicit higher titers of neutralizing antibodies in both animals and humans than post-fusion F proteins.
Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) designed disulfide, cavity-filling and other mutations that stabilize the Nipah F glycoprotein in the prefusion conformation and bind prefusion-specific antibodies. These mutations also increase protein expression yields up to 50-fold making the recombinant proteins easy to manufacture and amenable to the use of genetic immunization using nucleic acid or vector-based applications.
The stabilized prefusion state of the Nipah F glycoprotein may be an ideal vaccine immunogen to elicit broad potent Nipah neutralizing antibodies. First and second generation prefusion molecules have been designed and tested in small animals and results (immunogenicity and stability) appear promising.
This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404.
- Vaccine - to elicit potent neutralizing antibodies against the Nipah Env glycoprotein
Nipah prefusion F design has the following features compared to wild-type fusion glycoprotein:
- Robust stabilization
- Up to 50-fold increase in expression yields, making the recombinant proteins easy to manufacture
- Potential to link the recombinant glycoprotein to nanoparticles or oligomerization peptides