Prefusion-Stabilized Fusion (F) Glycoprotein Vaccine Immunogens For Human Metapneumovirus


Human metapneumovirus (hMPV) infections have been shown as a common cause of upper and lower respiratory diseases such as bronchiolitis and pneumonia in young children, the elderly, and other immunocompromised individuals. Studies show that infections by the non-segmented negative strand RNA virus begin with attachment and entry of viral glycoproteins that mediate fusion with host cellular membranes. Like for the human respiratory syncytial virus (hRSV), a viral entry is initiated by the fusion (F) protein. Given its role in hMPV entry, the F protein has thus been a target for eliciting neutralizing antibodies and development of novel protein-based therapeutic vaccines.

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) developed improved recombinant human metapneumovirus (hMPV) F proteins stabilized in the prefusion conformation that can elicit potent neutralizing antibodies against infection. Double and triple stabilized candidates were designed with inter-and intraprotomer disulfide mutations that increase protein production and show improved antigenic recognition by prefusion-specific antibodies. These second-generation immunogens constitute an improvement over the first generation constructs and are characterized by additional stabilization that results in optimal neutralization responses.

The second-generation stabilized prefusion hMPV F immunogens may be an ideal vaccine immunogen to elicit broad potent neutralizing antibodies against metapneumovirus infection, particularly in children and immunocompromised adults.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404.

Potential Commercial Applications: Competitive Advantages:
  • A promising vaccine immunogen to elicit broad potent neutralizing antibodies against metapneumovirus infection, particularly in children and immunocompromised adults
 
  • There are no approved vaccines or therapeutics against the second leading cause of pediatric viral lower respiratory tract infection in infants and young children
  • Second-generation hMPV F immunogens induce higher titer neutralizing responses than first-generation versions in mice


Inventors:

Peter Kwong (NIAID)  ➽ more inventions...

Yaroslav Tsybovsky (NIAID)  ➽ more inventions...

Ursula Buchholz (NIAID)  ➽ more inventions...

Peter Collins (NIAID)  ➽ more inventions...

Wing-pui Kong (NIAID)  ➽ more inventions...

John Mascola (NIAID)  ➽ more inventions...

Li Ou (NIAID)  ➽ more inventions...

Jason Gorman (NIAID)  ➽ more inventions...

Guillaume Stewart-Jones (NIAID)  ➽ more inventions...

Tongqing Zhou (NIAID)  ➽ more inventions...

Baoshan Zhang (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 63/017,581

Publications:
Liu, P., et al PMID 23761661
Battles, M. B., et al PMID 29142300

Licensing Contact:
Carol Salata, Ph.D.
Email: csalata@mail.nih.gov
Phone: 240-627-3727

OTT Reference No: E-131-2019-0
Updated: Jan 26, 2021