Creating Innovative Camelid Nanobody Approaches for Treatment of Severe Dengue
Abstract
Dengue, a disease caused by the dengue virus (DENV), is an emerging global health treat. There are currently no U.S. Food and Drug Administration-approved vaccines for dengue virus infections, and innovative therapeutics to limit disease morbidity are lacking. This is especially for those patients with potentially fatal Severe dengue – formally dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). We propose a dengue virus therapeutic for severe dengue based on the use of very tiny antibodies made from camels immunized with the DENV virus known as nanobodies (Nbs). Nbs are poorly immunogenic and will recognize many more dengue virus here I am binding sites with dengue virus neutralizing potential not recognized by the conventional antibodies. It is hypothesized that Nbs will provide an ideal immunologic therapeutic for military personnel stationed at or traveling to regions where DENV is known to occur without putting them at risk for adverse antibody-dependent reactions due to previous infections with viruses closely related to dengue virus, e.g., ZIKA virus. We propose to make a therapeutic Nb cocktail that will recognize the entire dengue virus (blocking cell attachment and infection) and as well as virus molecules such as one called Non-Structural Protein-1 or simply NS-1. The release of NS-1 from dengue virus-infected cells can sometimes cause blood vessels in various organs to become dangerously leaky – a hallmark of severe dengue. We will test for this using a variety of experimental methods. The therapeutic drug potential of camelid Nbs targeting Asian flu, hepatitis C virus, rabies, poliovirus, and rotavirus infection has been shown. Successful completion of the proposed studies will significantly improve mission readiness of the U.S. military against combating potential outbreak of dengue virus and thereby have significant impact on operational readiness of the troops, especially in regions where the virus is endemic and/or in the event of a local outbreak in the U.S. and its territories.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2220029
Entities
People
- Dennis Grab
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- United States Army