Conversations with Lipid Leaders: Dr. Susan Baldwin

The Conversations with Lipid Leaders Interview Series brings forward insights and experience from the communities most influential and upcoming scientists to stay connected to current colleagues and inspire the next generation of Lipid Leaders! Keep reading for our interview with Dr. Susan Baldwin!

Tell us a little bit about yourself (current role, background, family, etc.)

I work as a principal investigator focusing on vaccine development against Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) at Seattle Children’s Research Institute in Seattle. My primary research concentrates on characterizing immune reactions and efficacy following both prophylactic and therapeutic vaccine regimens in preclinical infectious disease models.

My interest in vaccine development began following undergraduate studies in microbiology. I first worked as a research associate in the lab that developed a successful feline leukemia virus vaccine. As a Ph.D. candidate studying under the mentorship of the late Professor Ian Orme, my research centered on novel vaccines against Mtb.

My family includes a husband and two very sweet golden retrievers.

Did you always envision yourself becoming a scientist? If not, what did you want to be when you grew up? Who influenced you to become a scientist?

Early in my college education, I envisioned a career in pediatric or veterinary medicine. Alternatively, because I loved painting, I also considered studying art. While pursuing my undergraduate studies in microbiology, a powerful influence inspiring me toward a career in science was Dr. Barbara Joyce who taught medical microbiology at Colorado State University. Dr. Joyce was the first genuinely accomplished woman scientist that I personally knew. And it was through her encouragement that I pursued a career in science.

What do you consider the greatest breakthrough in vaccine technology in recent years?

The discovery of key receptors (e.g., Toll-like receptors) on innate immune cells that recognize pathogen-associated molecular patterns (PAMPs). This breakthrough enabled utilizing innovative adjuvants to maneuver precise vaccine-mediated signaling cascades required for effective adaptive immunity.

What was your inspiration for getting involved in vaccine therapeutics and the study of adjuvants?

The complexities and challenges of developing an effective Mtb vaccine, together with the failure of the BCG vaccine to prevent adult pulmonary TB, inspired me to work toward this effort.

By combining a suitable therapeutic vaccine with a drug regimen, the possibility of reducing the duration of therapy and the risk of transmission of drug-resistant Mtb becomes possible. An effective therapeutic vaccine could enhance the immune system by killing bacteria that escape chemotherapeutic destruction based on either inadequate drug treatment or drug-resistance.

Could you briefly explain to our readers how adjuvants work and why it is difficult to point to a single mechanism of action for adjuvants?

Adjuvants are mixtures of molecules and chemicals that enable the stimulation of innate immune cells and guide the induction of effective vaccine-mediated cellular and humoral responses required to eliminate a pathogen. There are several different adjuvants and formulations that can activate cells in different ways. As an example, monophosphoryl lipid A (MPL) by itself signals through the TLR4 on dendritic cells and monocytes and induces chemokines and cytokines that can lead to a specific type of helper CD4+ T cell (T helper 1, or Th1) when it is combined with a specific vaccine antigen. But when MPL is formulated with an emulsion or with Alum, along with the same antigen, it can trigger the inflammasome pathway as well, making the adjuvant more potent, leading to an increased number of Th1 cells. By adding multiple components to an adjuvant, the efficacy of a vaccine or therapy can be enhanced.

What have been some recent advances in adjuvant technology? What might the future of vaccine technology look like if precision adjuvants are developed?

Some recent advances in adjuvant technology include the adjuvant systems from GlaxoSmithKline (GSK). The AS01 adjuvant, containing MPL (a TLR4 agonist), liposomes, and an extract called QS-21 (a saponin derived from the Quillaja saponaria soap-bark tree), is approved for use in human vaccines such as Shingrix. Shingrix is a recombinant zoster vaccine that is 91-97% effective against shingles. AS01_E is also being used in a promising clinical tuberculosis vaccine, called M72, targeted against the development of pulmonary TB disease in humans. In addition, along with Dr. Rhea Coler and colleagues, I am researching another TB vaccine in the clinical pipeline, ID93+GLA-SE. This vaccine uses a synthetic version of a TLR4 agonist adjuvant mixed with an emulsion.

Beyond enhancing the efficacy of both vaccines and therapies, precision adjuvants will additionally permit the creation of safer vaccines through dose-sparing effects; broadened immune responses to pathogens known to mutate (e.g., influenza, SARS-CoV-2, and HIV viruses); and longer duration of memory immune responses.

What are your hobbies? What do you like to do outside of the lab?

Cooking is one of my favorite hobbies; The magazine “Cooks Illustrated” describes much of the chemistry and physics of the ingredients and cooking processes. This appeals to my nerdy side. Another reason I enjoy cooking is that it provides the opportunity to host dinner parties for friends and family. I also find that exploring the food and international culture in Seattle and the Pacific Northwest with my husband and my friends is a favorite pastime of mine.

What was your favorite and least favorite course in school? What was the hardest course for you while you were in school?

My favorite class in school was a graduate-level creative science writing course taught by Dr. Gerry Callahan at Colorado State University. Graduate students that took the course included both science and literature majors. It was absolutely enlightening and wonderful to receive criticism and comments on my science writing from a diverse collection of perspectives. While I now have an excellent appreciation for world history, by far, the most challenging courses early in my training were those required history classes.

We would like to thank Dr. Susan Baldwin for taking time to catch up with us!