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

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. An animal study demonstrated that after immunization 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.

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: 

  • Platform for multimerized immunogen presentation and vaccine design.

  • Vaccines for pathogens that use genetic diversity to escape the immune response.

  

Competitive Advantages: 

  • 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).

Development Stage: In vivo testing (rodents)

Inventors: Peter Kwong (NIAID), Ivelin Georgiev (NIAID), Michael Gordon Joyce (NIAID), Masaru Kanekiyo (NIAID), Aliaksandr Druz (NIAID), Ulrich Baxa (NIAID), Joseph Van Galen (NIAID), Rita Chen (NIAID), Cheng Cheng (NIAID), John Mascola (NIAID), Yaroslav Tsybovsky (Leidos Biomedical Research, Inc), Yongping Yang (NIAID), Paul Thomas (NIAID), Barney Graham (NIAID).

 

Publications:  Georgiev, Ivelin S., et al., ACS Infectious Diseases (2018) 4 (5), 788-796.

Intellectual Property: U.S. Patent Application No. 62/355,212 filed 06/27/2016; PCT Application No. PCT/US2017/039595 filed 06/27/2017 (pending). 



Licensing Contact: Barry Buchbinder, Ph.D., 240-627-3678; barry.buchbinder@nih.gov

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NIAID’s technology transfer office, TTIPO, is a one-stop resource for organizations interested in partnering with NIAID to access, develop, and manage the translation of research discoveries into medically beneficial products. TTIPO seeks to expand NIAID’s innovation pipeline with existing and new partners in areas such as newly emerging and re-emerging infectious diseases (e.g., dengue, Zika, Ebola, influenza, methicillin-resistant Staphylococcus aureus and HIV/AIDS), biodefense (e.g., smallpox and anthrax), and immune-mediated diseases (e.g., asthma and allergy).

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