Self-assembling Insect Ferritin Nanoparticles for Display of Co-assembled Trimeric Antigens


Antigens on the surface of virus particles are displayed in a regular, repetitive pattern which facilitates B cell activation. Presenting trimeric antigens on engineered particles that mimic the geometric patterns observed for native viral proteins can lead to an improved host antibody response.

Self-assembling globular ferritin nanoparticles have previously been used to display multiple copies of a co-assembled trimeric antigen to the immune system. However, prior ferritin nanoparticle technologies only permit a random co-assembly of diverse trimeric antigens, and therefore cannot guarantee the pattern and ratio of diverse trimeric antigens on a single ferritin nanoparticle.

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases are developing novel recombinant ferritin nanoparticles that are based on insect ferritin proteins, and that have been engineered to display two different trimeric antigens in a defined ratio and geometric pattern. This system has been tested with antigens derived from HIV-1 envelope (Env) and influenza hemagglutinin (HA). Interestingly, when guinea pigs are immunized with ferritin nanoparticles displaying two different trimeric antigens, induced B cells could simultaneously recognize both trimeric antigens, thus leading to an immune response with improved neutralization breadth.

This technology can be used as a platform for multimerized display of trimeric antigens such as viral type I fusion glycoproteins, and may be applied to many high-priority vaccine targets, such as HIV-1, influenza, respiratory syncytial virus, parainfluenza viruses, and coronaviruses.

Potential Commercial Applications: Competitive Advantages:
  • Platform for multimerized immunogen presentation and vaccine design.
  • Vaccines for pathogens that use genetic diversity to escape the immune response.
 
  • Particles have equal fractions of two different antigens in a specific configuration on the nanoparticle surface (unlike regular ferritin used previously)
  • Designed particles have a geometry that allows for attachment of trimeric antigens (unlike the native insect ferritin).


Related Invention(s):
E-293-2011-0
E-531-2013-0
E-060-2015-0


Inventors:

Masaru Kanekiyo (NIAID)  ➽ more inventions...

Barney Graham (NIAID)  ➽ more inventions...

Peter Kwong (NIAID)  ➽ more inventions...

Ivelin Georgiev (NIAID)  ➽ more inventions...

Michael Joyce (NIAID)  ➽ more inventions...

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

Aliaksandr Druz (NIAID)  ➽ more inventions...

Ulrich Baxa (NIAID)  ➽ more inventions...

Joseph Van Galen (NIAID)  ➽ more inventions...

Cheng Cheng (NIAID)  ➽ more inventions...

John Mascola (NIAID)  ➽ more inventions...

Yaroslav Tsybovsky

Yongping Yang (NIAID)  ➽ more inventions...

Paul Thomas (NIAID)  ➽ more inventions...

Rita Chen (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 62/355,212
PCT Application No. PCT/US2017/039595
US Application No. 16/312,166

Publications:
Georgiev I, et al. PMID 29451984

Licensing Contact:
Barry Buchbinder, Ph.D.
Email: BBuchbinder@niaid.nih.gov
Phone: 301-496-2644

OTT Reference No: E-270-2015-0
Updated: Oct 17, 2018