Since 1964, the Lindsley F. Kimball Research Institute (LFKRI) has conducted groundbreaking research, resulting in numerous landmark patents and licenses and new blood-related products, techniques, and therapies — all of which have a direct humanitarian impact.
Today, LFKRI remains at the forefront of blood research by leveraging the resources and expertise of New York Blood Center Enterprises (NYBCe) to further our understanding of blood diseases, infectious diseases, and improve patient outcomes.
LFKRI currently consists of 20 pioneering investigators studying transfusion medicine, cell therapy, hematology, infectious diseases, and epidemiology. One such investigator is Sara Lustigman, PhD.
In addition to being a Member of LFKRI, Dr. Lustigman is the Head of the Laboratory of Molecular Parasitology. The Lab’s main focus is finding novel means to support the prevention of onchocerciasis, or “river blindness,” and lymphatic filariasis, also known as elephantiasis. In August 2021, Dr. Lustigman was also awarded a 5-year NIH U01 collaborative grant from the National Institute of Allergy and Infectious Disease to improve anti-viral vaccine responses in the elderly.
Recently, Dr. Lustigman sat down with NYBCe representatives to help others learn more about these ongoing projects and how they advance the organization’s lifesaving mission.
Q: How long have you been with the Enterprise?
Dr. Lustigman: I’ve been with the New York Blood Center and the Lindsley F. Kimball Research Institute for 33 years. It’s hard to believe!
Q: In your time at NYBCe, which areas of research have you primarily focused on?
Dr. Lustigman: I was originally recruited by New York Blood Center to help develop a vaccine against river blindness. My job was to develop a new model system that we could use to study vaccine development, identify potential vaccine candidates, and then validate their effectiveness using different animal models before moving to clinical development.
Our Lab also has been studying the biology of Onchocerca volvulus, the causative agent of this disease. Information gained by studying the parasite’s basic biology and host-parasite interactions has allowed the identification of key pathways and molecules that are essential for parasite development, propagation, and survival. We use this information to identify new therapeutic tools.
Over the years, we’ve identified more than 30 O. volvulus larval antigens of which 7 were proven to be protective against infection by third-stage larvae in a mouse model. We also selected the best two O. volvulus protective vaccine antigens with a proven production pathway and with proven efficacy in two small-animal models when formulated with alum and or Advax-2: Ov-103 and Ov-RAL-2 for pre-clinical development. These antigens exhibit the highest probability for success at inducing protective immunity in humans.
River blindness is still a crucial area of study. Most of my on-site involvement today is focused on developing potency assays for the vaccines. In addition, and over the past 10 years, I’m also managing the pre-clinical and clinical vaccine development project with an international group of scientists from Africa; Europe; the United Kingdom; Seattle, Washington; Houston, Texas; Washington, D.C.; and more as part of the TOVA Initiative. TOVA stands for “The Onchocerciasis Vaccine for Africa.”
TOVA’s goal is to take at least one or two vaccine candidates through Phase I trials by 2025 and Phase II trials by 2030. To achieve this, we’re working on large-scale production of vaccines in compliance with Current Good Manufacturing Practice (cGMP) regulations, and first-in-human safety trials.
So, we’ve come a long way from our proof of concept 30 years ago. Our goal is for the onchocerciasis vaccine to have at least 50% efficacy of inhibiting incoming worms and 90% reduction in parasite transmission that is mediated with what we call microfilaria.
We don’t think this vaccine will be the only solution to onchocerciasis. Think about COVID-19. Vaccines are great but having vaccines and drugs that mitigate symptoms is even better. We believe we need multiple treatment options that work together synergistically. We therefore are also focused on identifying novel therapeutic and/or prophylactic drugs that can further support the goal of elimination.
Q: What are some of the biggest obstacles you and the Lab have had to overcome during this 33-year project?
Dr. Lustigman: I would say funding. Diseases like ebola, malaria, and tuberculosis generally receive a lot of funding. But onchocerciasis is considered a neglected disease — not because it’s unimportant, but because it’s financially neglected. There are currently seven neglected tropical diseases caused by worm infections as defined by the World Health Organization (WHO).
Q: What about your biggest accomplishment?
Dr. Lustigman: The completion of the genome of this parasite. This was a huge breakthrough because this was the first parasitic nematode where we were able to sequence the genome based on its chromosomes — not just a database of sequences. Now, this genome is being used to determine the genome structures of other worm parasites.
This was an international effort, and it took us two years to write the paper. But it was personally one of my top scientific achievements in addition of course of seeing the light at the end of the tunnel for the development of a vaccine against onchocerciasis.
Q: We understand your research on onchocerciasis resulted in the development of a novel vaccine adjuvant, leading to a recent 5-year NIH U01 collaborative grant. Congratulations! Can you tell us more about this grant and how onchocerca is involved with vaccine adjuvants?
Dr. Lustigman: Our Laboratory studies the ability of O. volvulus to influence the immune system and reduce its ability to fight the infection. We do this by studying the immunomodulatory properties of distinct parasite proteins.
Mainly, we’ve identified and now are focused on studying a naturally occurring secreted protein from O. volvulus (rOv-ASP-1) with intrinsic immunostimulatory properties that we have established to be 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.
We’ve developed an effective, safe protein adjuvant called rASP-1 that can be using in a simple aqueous formulation of various vaccine antigens and 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 against various pathogens. This research has implications for the preventive treatment of various infectious diseases.
The grant will be used to help us learn more about how this protein adjuvant works. The idea is, once we know how it works, we can tailor vaccines to be effective in various populations.
Q: How would this finding impact research on vaccine unresponsiveness — particularly in the elderly?
Dr. Lustigman: As you age, your immune system declines to some extent. You produce fewer B cells, and T cell responses decrease. So we’re asking, can we reverse this unresponsiveness by adding the protein adjuvant alone or using combinatory adjuvants?
We know now that rASP-1 works through the body’s innate cells. So, what happens if we combine it with other innate adjuvants and get synergy? One molecule likely won’t reverse the unresponsiveness of aged people’s immune systems. But we think we can do it with multiple adjuvants and therefore modify the immune response in such a way that when you get vaccinated, or even infected by a pathogen, your body responds as if you’re young.
We will be working on this for the next five years in collaboration with The Jackson Laboratory for Genomic Medicine.
Q: What do you like most about your research and about working at New York Blood Center Enterprises?
Dr. Lustigman: I’m very grateful that I’ve stayed here all these years. I love New York, and I enjoy working at a research institute.
I’m also a curious person. Discovering new things — that’s what keeps me going. I love to discover new things and use the data we’ve generated to come up with new hypotheses and ask more questions.
As a nonprofit organization, New York Blood Center Enterprises relies on philanthropy to support different aspects of our lifesaving mission.
If you’d like to support Dr. Lustigman and the Laboratory of Molecular Parasitology’s research on onchocerciasis, lymphatic filariasis, and vaccine responses in the elderly, please consider giving online now. You can also contact the Office of Philanthropy directly to learn more about NYBCe’s philanthropic needs and download the 2021 Community Impact Statement to learn more about the direct humanitarian benefits of this groundbreaking blood research.