Sara Lustigman, PhD
The focus of our lab’s research is to find novel means to support the prevention ofonchocerciasis, also known as river blindness, and lymphatic filariasis, also known as elephantiasis. To achieve this we have been studying the biology of Onchocerca volvulusand Brugia malayi, the causative agents of these diseases, respectively. Information gained by studying the basic biology and host-parasite interactions has allowed the identification of key pathways and molecules that are essential for parasite development, propagation and /or survival. While many aspects of our research are basic, our ultimate goal is to identify new strategies by which humans can be protected from these parasitic infections by either chemotherapeutic (drugs) or immunological (vaccines) means.
Over the years we have identified more than 30 O. volvulus larval antigens of which 7 were proven to be protective against infection by third-stage larvae in the mouse model.We have recently made considerable progress and identified 2 O. volvulus protective vaccine antigens with a proven production pathway and with proven efficacy in 2 small-animal models when formulated with alum: Ov-103 and Ov-RAL-2. These antigens exhibit the highest probability for success at inducing protective immunity in humans. We are ready to move forward to the next stage on the critical path to an onchocerciasis vaccine development for Africa (http://www.riverblindnessvaccinetova.org).
The laboratory also studies the ability of O. volvulus to influence the immune system and reduce its ability to fight infection by studying the immunomodulatory properties of distinct parasite proteins. In particularly, we are focused on a naturally occurring secreted protein from O. volvulus (rOv-ASP-1) with intrinsic immunostimulatory properties that it is a powerful immunostimulatory adjuvant; it promotes a balanced Th1/Th2 antibody response and cellular responses to several soluble vaccine candidate antigens, and commercial inactivated viral vaccines, including trivalent-inactivated flu vaccines. Our long-term objective is to develop this highly effective and safe protein adjuvant in a simple aqueous formulation of vaccines that also requires a much lower dose of antigen. By enhancing vaccine efficacy in this way, we can effectively increase the number of vaccine doses available that can be administered to humans to boost their immune response. This research has implications for the preventive treatment of various infectious diseases.
The laboratory is engaged in a collaborative research effort to discover new drug therapies for the treatment of river blindness. The goal is to identify a novel, potent macrofilaricidal drug candidate that is capable of killing adult worms. In addition, the lab is studying proteins that are possibly involved in the endosymbiotic relationship between the filarial worms and the endosymbiotic bacterium of the genus Wolbachia that they harbor. These endobacteria are essential, as elimination of the endosymbiont leads to arrested larval development and the sterilization of the adult female parasite. It is expected that by identifying a select number of Wolbachia genes and their interacting partners in B. malayi involved in the symbiotic relationship, it will be possible to also identify processes within B. malayi and Wolbachia that may be sensitive to interference with new drugs.
- Denis Voronin, PhD, Assistant Member
- Jovvian George Parakkal, PhD, Research Fellow
- Shabnam Jawahar, MSc, Research Assistant
- Nancy Tricoche, MS, Sr. Research Assistant
NIH R21 AI131701 Lustigman (PI) 2/1/2017- 1/31/2019 “Innovative 3-D In Vitro Culturing Systems for Filarial Worms”
NIH R01 AI078314 Lustigman (PI) 08/2009 - 02/2022 "The Development of a Recombinant Vaccine Against Human Onchocerciasis"
NIH U01 AI124260 Lustigman/Jiang (co-PIs) 08/2016 – 07/2021 “Enhancing Potency of the MERS Vaccine by a Novel ASP-1+Alum Adjuvant Combination"
NIH R56 AI118936 Lustigman/ Ghedin/Unnasch (co-PIs) 03/2016 – 02/2018 (NCE) “Functional Interplay Between Brugia and its Wolbachia Symbiont”
NIH R01 AI105431 Lustigman/ Bottazzi /Shen (co-PIs) 01/2013 – 12/2018 “Development of a Novel Adjuvant for Vaccine Sparing”
NIH R21AI127639 Sakanari (PI) 12/2016 – 11/2018 “Novel Therapeutics for Treatment of River Blindness and Lymphatic Filariasis.”
- Bill and Gates Foundation OPP1171883 Lustigman (PI) 3/2017 -4/2018 “Production of Onchocerca volvulus larvae to support Macrofilaricide Drug Accelerator (MacDA) Program.”
- 1999 Method of use of phthalocyanines to inactivate blood borne parasites: Paul Gottlieb, Ehud Ben-Hur and Sara Lustigman (U.S. Patent No. Us 5,985,331)
- 2004 Angiogenic Onchocerca volvulus proteins and uses thereof: Sara Lustigman, Eric Pearlman and Thomas Unnasch (U.S. Patent No. Us 09-541,759)
- 2010, 2015 Adjuvancy and immune potentiating properties of natural products ofOnchocerca volvulus: MacDonald AJ and Lustigman S (U.S. Patent No. US 7,700,120 B2 and US 9,017,699 B2)