The research career of Brandon Wilder, Ph.D., is inspired by the lush waterways near his childhood Florida home.
Wilder — now an immunologist and assistant professor at Oregon Health & Science University's Vaccine and Gene Therapy Institute — first fell in love with science in middle school, while admiring tiny swamp life. He became fascinated with biology when the microorganisms suddenly became visible to him through an old microscope, which had been discarded from the local diagnostic laboratory where his mother worked as a medical technician.
"Science was the only thing I was really good at," Wilder recalls with a smile. "I would have preferred to be a professional NBA player, but I stopped growing in sixth grade, so that didn't work very well. I was in high school when I decided that I wanted to do gene therapy research, and I'm almost there."
Today, 39-year-old Wilder is focused on finding lasting, safe and effective ways to both prevent and treat malaria, which infected 249 million people and killed 608,000 worldwide in 2022. The World Health Organization estimates that every minute, a child younger than 5 dies of malaria. Even though malaria has likely been a leading cause of death and illness for thousands of years, Wilder is optimistic that research will soon turn around those overwhelming odds.
Advancing the malaria fight
Shortly after joining OHSU in 2018, Wilder established the university's only insectary. The small, secure facility is where he and colleagues raise and study up to 200,000 mosquitoes, which spread the malaria-causing Plasmodium parasite.
In his lab, he and 10 other scientists work to better understand how the human immune system responds to a malarial infection, and use that knowledge to make better malaria drugs and vaccines. With Gates Foundation support, his lab has been evaluating how well a variety of lab-made protective proteins, known as monoclonal antibodies, can protect against malaria in a humanized mouse model.
Wilder's research frequently involves collaborating with experts in other fields, and outside his primary appointment at OHSU's Vaccine and Gene Therapy Institute. Many of his OHSU research partners are associated with OHSU's Oregon National Primate Center and the OHSU School of Medicine's Department of Molecular Microbiology and Immunology, where Wilder is also an affiliate.
The fight against malaria has recently taken a few large steps forward. In 2022, the NIH published clinical trial results that found a monoclonal antibody is up to 88% effective in preventing malaria infection in adults. Last month, a follow-up study found it is also 77% effective in children. Such protection is tremendous, but making antibodies in the lab can be too expensive for low- and middle-income countries.
And two malaria vaccines – dubbed R21 and RTS,S – have recently become available after decades of development. In October 2023, the World Health Organization recommended that either vaccine be given to children in areas where malaria is endemic. Both vaccines target a single protein that is needed for the Plasmodium parasite to move into the liver after an infected mosquito bites a person's skin. Each vaccine prevents up to 75% of malaria cases when they're given seasonally in areas of high transmission.
However, these vaccines can't help if the parasite moves onto its next stage in their human host — when it transitions from the liver and enters the bloodstream. At that point, Plasmodium no longer needs the protein that the current vaccines target, meaning those vaccines can't help people who are in the bloodstream stage of a malarial infection.
That's why Wilder wants to create a multivalent malaria vaccine that can target Plasmodium before, during and after the liver-stage of infection.
New partnerships are helping his multivalent dreams inch toward reality. Wilder is part of a seven-center, Canada-led research collaboration working together to evaluate a variety of different vaccines, with nonhuman primates serving as a critical model before the vaccines can be studied in humans. The consortium's research is planning to use existing malaria vaccines, including R21 and others that are in development. The team will confirm that nonhuman primates are a good model for how humans respond to vaccines. They will also test several variables, including how to combine multiple vaccines most effectively and how the length of time between doses impacts immune response.
Separately, Wilder recently received a grant from the Hypothesis Fund, which supports innovative, early-stage health and climate research. The grant is enabling him to test the audacious idea that antibodies can fight pathogens inside cells; immunology has long held that they only work outside of cells. He's already conducted limited research in a humanized mouse model that indicated when Plasmodium reaches the liver of its host, antibodies can clear out the parasite from inside liver cells.
The new funding is enabling him to repeat that earlier research at a larger scale. To scale up, Wilder is partnering with Fikadu Tafesse, Ph.D., associate professor of molecular microbiology and immunology in the OHSU School of Medicine, to use alpacas to make tiny antibodies called nanobodies. If this follow-up research produces findings that are similar to Wilder's earlier studies, it could lead to new ways to treat not just malaria, but also numerous other diseases.
He also has NIH support for a nonhuman primate study that is exploring the potential of using a different biological tool — immune cells known as T cells — to prevent malaria infections.
'Do something important'
Thinking back to his youth spent in Floridan swamps, he's glad it led him to a career in science.
"I get to do something important with my research," Wilder says.
A fan of "team science," or collaborative research conducted across scientific specialties and labs, Wilder is also proud that he gets to do research with others at OHSU and around the world who are equally determined to make a difference.
"It's rewarding to see so many people rally around this," he says.
Wilder earned a doctorate degree in microbiology and immunology from the University of Florida in 2012. He completed a postdoctoral fellowship at the Center for Infectious Disease Research in Seattle, and later became a research assistant professor there. He joined the OHSU Vaccine and Gene Therapy Institute in 2018. Between 2019 and 2023, Wilder also worked part-time as a unit leader of immunology and vaccine development at the Naval Medical Research Unit-SOUTH in Lima, Peru.
All research involving animal subjects at OHSU must be reviewed and approved by the university's Institutional Animal Care and Use Committee (IACUC). The IACUC's priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. No live animal work may be conducted at OHSU without IACUC approval.
