Avoiding antibody-dependent enhancement enables dengue prevention and treatment

Background:

Dengue virus is one of the most widespread vector-borne viral pathogens in the world. Nearly 400 million dengue virus infections occur each year, resulting in approximately 20,000 deaths. In addition, dengue-associated illness comprises an annual global economic burden of around $9 billion USD. While dengue is rare in the continental U.S., warming patterns across the Southern U.S. are expanding the range of mosquito species capable of transmitting the virus. There is currently no FDA-approved dengue vaccine for use in individuals who have not experienced a previous dengue virus infection, or any approved monoclonal antibody therapy for the prevention or treatment of acute dengue.

Technology overview:

This Upstate Medical University technology overcomes a major challenge in dengue prevention and treatment: Antibody-Dependent Enhancement (ADE). This phenomenon causes IgG isotype antibodies that recognize dengue virus to enhance infection in individuals with waning or incomplete antiviral immunity. Our technology circumvents this challenge by 1) providing immediate immunity to infection by providing dengue virus neutralizing antibodies, and 2) utilizing an IgA1 antibody construct that will preserve antibody function while being incapable of facilitating ADE like IgG antibodies. This not only provides immediate protection against dengue infection in individuals who have not had dengue before, but also reduces the risk of developing severe disease in individuals with preexisting/suboptimal dengue immunity.

Advantages:

Enables the development of dengue prevention and treatment options by avoiding Antibody Dependent Enhancement.

Applications:

There are several potential applications for this product:

Travelers: reduce the risk of infection while in dengue-endemic areas.
US Military: reduce the risk of infection and prevent the loss of combat effectiveness when deployed in dengue-endemic areas.
Residents of dengue endemic areas during dengue transmission seasons
Relatives, neighbors, or other living in close proximity to an individual experiencing an acute dengue infection.

Intellectual property summary: Patent application submitted, Provisional patent, US Provisional Filed, 63/235,325

Stage of development: Technology Readiness Level (TRL): 3 - Experimental proof of concept.

Licensing status: This technology is available for licensing and will be of value to any company or institution involved in preventing and treating dengue. This includes: