Brandon Wilder, Ph.D.

Malaria is one of the oldest and deadliest diseases in human history. Each year it takes the lives of roughly 3-4 times as many children as cancer and puts nearly half the world’s population at risk of infection. The parasite which causes malaria, Plasmodium, is more complex than the viruses and bacteria for which we have developed vaccines thus far. Plasmodium has also been evolving to escape our immune defenses for millennia as compared to the decades or perhaps centuries of most endemic pathogens. These factors present enormous hurdles for malaria vaccine development. The two recently approved malaria vaccines—RTS,S and R21—are built on conventional principles used to make effective vaccines against viruses and bacteria and as a result have modest, short-lived efficacy. Given the scale of malaria, this still represents a watershed moment for humanity in the amount of suffering that will be avoided. Our central tenet is that if we are to going to make sustainable gains to control or eliminate malaria, we must employ more unconventional and sophisticated means to match perhaps the most unconventional and sophisticated pathogen in human history.

The complex Plasmodium life cycle starts when an infected mosquito injects tens to hundreds of parasites into the skin. The parasite then actively crosses through a blood vessel and enters the blood circulation with the goal of reaching the liver. Once in the liver, it will traverse through multiple liver cells before settling in a single hepatocyte where it will grow to form roughly 50,000 parasites over a week. During this time there are no symptoms of infection. After this week, the 50,000 parasites emerge in a radically changed life stage which cyclically infects and kills red blood cells. As parasite numbers expand into the billions, the infected person is susceptible to malaria-associated disease and death. During this time, a subset of parasites will develop into yet another form that can then be ingested by a new mosquito in which the parasite will undergo an equally complex infection where it prepares to be injected into a new human host and continue the infection cycle.

Such a prolonged and multi-faceted life cycle allows for multiple points where the immune system can intervene and stop the infection. Yet this also has been the focal point of a millennia-long evolutionary arms race between two sophisticated organisms. Using unconventional approaches such as weakened parasites that infect but do not cause disease, Brandon Wilder and colleagues are uncovering the mechanisms by which the immune system can overcome malaria infection or prevent it all together. Rather than trying to reduce these interactions into digestible components, the Wilder group is focused on how to understand these interactions within the host and parasite dynamic. Importantly, we aim to translate these observations into more potent vaccines or interventions. We do this by combining data from human studies, non-human primate models of malaria, humanized mice and traditional rodent models.

For example, working with researchers from across the globe, the Wilder lab is using humanized mice to help advance monoclonal antibody therapies for malaria and to answer critical questions about how antibodies targeting multiple life stages can augment vaccine efficacy. In non-human primates, the Wilder lab is exploring the intersection between infection and vaccination to understand what a protective immune response looks like in the liver looks like, how it changes through vaccination and how this is impacted by previous infection—questions impossible to answer in humans. Finally, in traditional mouse models we are exploring a new class of antibody that targets the parasite while it is inside the cell. This is a time when antibodies are thought to be ineffective, and we are interested in exploring the potential of this uncommon phenomenon. Together, we hope that one or more of these concepts can contribute to better, more sustainable interventions against this deadly disease.


Brandon Wilder attended the University of Florida where he received his B.S. in 2006 and his Ph.D. in Immunology and Microbiology in 2012. He then did his postdoctoral fellowship with Stefan Kappe at the Center for Infectious Disease Research in Seattle, WA where he studied protective immune responses to malaria and eventually finished as a Research Assistant Professor in 2018. He then joined the OHSU Vaccine and Gene Therapy Institute in as an Assistant Professor where he remains. From 2019-2023, he also split his time serving as the Unit Head of Immunology and Vaccine Development in the Department of Parasitology at the Naval Medical Research Unit-SOUTH in Lima, Peru.

Selected publications

  1. Julio Ventocilla, L. Lorena Tapia, Lisa Sperling, Reynaldo Ponce, Adriano Franco, Mindy Leelawong, Joao C. Aguiar, G. Christian Baldeviano, Brandon K. Wilder. Analysis of Pre-Erythrocytic Immunity During Plasmodium Vivax Infection Reveals a Diversity of Responses That is Partially Due to Blood Stage Cross-Reactivity, 25 May 2021, PREPRINT available at Research Square.
  2. MacMillen Z, Hatzakis K, Simpson A, Shears MJ, Watson F, Erasmus JH, Khandhar AP, Wilder B, Murphy SC, Reed SG, Davie JW, Avril M. Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine. NPJ Vaccines. 2024 Jan 10;9(1):12. doi: 10.1038/s41541-023-00799-4. PubMed PMID: 38200025
  3. Wilder BK, Vigdorovich V, Carbonetti S, Minkah N, Hertoghs N, Raappana A, Cardamone H, Oliver BG, Trakhimets O, Kumar S, Dambrauskas N, Arredondo SA, Camargo N, Seilie AM, Murphy SC, Kappe SHI, Sather DN. Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and may enhance protection of anti-CSP monoclonal antibodies. NPJ Vaccines. 2022 May 26;7(1):58. doi: 10.1038/s41541-022-00480-2. PubMed PMID: 35618791
  4. Aleshnick M, Florez-Cuadros M, Martinson T, Wilder BK. Monoclonal antibodies for malaria prevention. Mol Ther. 2022 May 4;30(5):1810-1821. doi: 10.1016/j.ymthe.2022.04.001. Epub 2022 Apr 5. Review. PubMed PMID: 35395399.
  5. Minkah NK, Wilder BK, Sheikh AA, Martinson T, Wegmair L, Vaughan AM, Kappe SHI. Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites. Nat Commun. 2019 Sep 2;10(1):3950. doi: 10.1038/s41467-019-11819-0. PubMed PMID: 31477704
  6. Kisalu NK, Idris AH, Weidle C, Flores-Garcia Y, Flynn BJ, Sack BK, Murphy S, Schön A, Freire E, Francica JR, Miller AB, Gregory J, March S, Liao HX, Haynes BF, Wiehe K, Trama AM, Saunders KO, Gladden MA, Monroe A, Bonsignori M, Kanekiyo M, Wheatley AK, McDermott AB, Farney SK, Chuang GY, Zhang B, Kc N, Chakravarty S, Kwong PD, Sinnis P, Bhatia SN, Kappe SHI, Sim BKL, Hoffman SL, Zavala F, Pancera M, Seder RA. A human monoclonal antibody prevents malaria infection and defines a site of vulnerability on Plasmodium falciparum circumsporozoite protein. Nature Medicine. 2018. 24(4): 408-416. PMID: 29554083
  7. Isabelle Zenklusen, Joshua Tan, Antonio Lanzavecchia, Stephen L. Hoffman, Jongo Said, Salim Abdulla, Claudia Daubenberger*, Brandon K. Sack*. Immunization of malaria pre-exposed Tanzanian adults with aseptic, purified, irradiated Plasmodium falciparum sporozoites elicits long-lived sporozoite-specific IgM antibodies which are capable of inhibiting sporozoite invasion in vitro. Journal of Infectious Diseases. 2018. Apr 23;217(10):1569-1578. *Equal contribution PMID: 29438525
  8. Sack BK, Mikolajczak SA, Fishbaugher M, Vaughan AM, Flannery EL, Nguyen T, Betz W, Jane Navarro M, Foquet L, Steel RWJ, Billman ZP, Murphy SC, Hoffman SL, Chakravarty S, Sim BKL, Behet M, Reuling IJ, Walk J, Scholzen A, Sauerwein RW, Ishizuka AS, Flynn B, Seder RA, Kappe SHI. Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice. 2017. npj Vaccines 2(1): 27. PMID: 29263882
  9. Sack BK, Keitany GJ, Vaughan AM, Miller JL, Wang R, Kappe SH. Mechanisms of stage-transcending protection following immunization of mice with late liver stage-arresting genetically attenuated malaria parasites. PLoS Pathog. 2015 May 14;11(5):e1004855. PubMed PMID: 25974076; PubMed Central PMCID: PMC4431720

Complete bibliography