Use a humanized monoclonal antibody as an emergency prophylactic and therapeutictreatment against human Q fever

Abstract Q fever is a worldwide zoonotic disease that is caused by the obligate intracellular Gram-negative bacterium, Coxiella burnetii. The highly infectious nature of C. burnetii and its unique resistance to heat, ultraviolet light, and other environmental factors make this organism an important zoonotic pathogen, and it can be potentially useful in bioterrorism and biological warfare. Human Q fever can develop into a severe chronic, potentially fatal disease, and there is no FDA-approved vaccine available for the prevention of human Q fever in the US. Additionally, it is difficult to treat chronic Q fever patients with various antibiotic regimens. Therefore, ZenVax LLC intends to develop safe and effective prophylactic and therapeutic treatments for the prevention and treatment of human Q fever. ZenVax is a startup biotech company, focused on the development of novel vaccines and immunotherapeutics for the prevention of infectious diseases caused by microbial pathogens. This Small Business Technology Transfer (STTR) Phase I project aims to prove the concept that monoclonal antibody (mAb) can be utilized as a prophylactic and therapeutic strategy against an intracellular bacterial pathogen. Despite C. burnetii being an obligate intracellular bacterial pathogen, ZenVax’s recent work demonstrated that passive transfer of a C. burnetiid virulent Nine Mile phase I lipopolysaccharide targeted mouse mAb 1E4 provided significant protection against C. burnetii aerosol infection in SCID mice, and a humanized variable fragment of 1E4 was able to inhibit C. burnetii infection in mice as well as in human macrophages. These results demonstrate the possibility of using humanized 1E4 (h1E4) as a rapid, effective emergency treatment for the control of human Q fever. Thus, the overall objective of this STTR Phase I project is to prove the feasibility of using h1E4 as an effective prophylactic and therapeutic treatment against human Q fever. To achieve this objective, we propose two specific aims to test the central hypothesis that passive administration of h1E4 will provide immediate protection against C. burnetii infection. Aim 1 will validate the prophylactic efficacy of h1E4 against C. burnetii infection with acute and chronic Q fever isolates in mice. Aim 2 will evaluate the therapeutic efficacy of h1E4 against C. burnetii infection with acute and chronic Q fever isolates. This project is significant because it will establish the “proof of principle” not only for the prevention and treatment of human Q fever, but also for a broad platform/approach against other intracellular bacterial pathogens in general. Upon completion of the Phase I project, we expect to demonstrate that h1E4 will be an effective emergency prophylactic and therapeutic treatment for control of human Q fever, and next, h1E4 will be manufactured under GMP/GLP conditions for further safety and efficacy testing in the Phase II project.