Background on Malaria Vaccine Development
The burden of malaria remains intolerable, causing over 200 million clinical cases and 400,000 deaths each year, with pregnant women and children in Africa bearing the greatest risk. Antimalarial drugs and insecticide-treated nets have effectively reduced malaria cases over the last few decades, but progress has stalled in recent years as these measures decline in efficacy. Vaccination remains a key strategy to bolster control efforts towards reduction and elimination of this scourge.
Malaria vaccines target the major stages of the Plasmodium life cycle and are distinguished by three distinct types: 1) Pre-erythrocytic (also called anti-infection) vaccines aim to prevent sporozoite invasion into the liver after inoculation by a feeding mosquito; 2) Blood stage (also called anti-disease) vaccines target asexual parasite forms that emerge from the liver to infect erythrocytes and multiply, causing clinical illness; and 3) Mosquito stage (more widely known as “transmission-blocking”) vaccines target sexual stages of the parasite, eliciting antibodies that are taken up mosquitoes in a bloodmeal, which then halt parasite development in the mosquito midgut, preventing further transmission to the next human host.
The Laboratory of Malaria Immunology and Vaccinology (LMIV)
LMIV was commissioned in 2009 to conduct basic and applied research relevant to malaria immunology and vaccine development, pursue novel vaccine concepts, produce prototype malaria vaccines, and conduct early-phase clinical trials of promising vaccine candidates. Our overarching goal is to develop malaria vaccines that will reduce severe disease and death among African children and pregnant women and eliminate malaria from low-transmission areas of the world.
LMIV has an organizational structure that encompasses both basic discovery and product development within a small, integrated team. Discovery sections within LMIV conduct basic research on malaria pathogenesis and immunology, with emphasis on studies in humans who are naturally or experimentally infected with malaria parasites. In parallel, the Vaccine Development Unit operates more like a small biotech firm than a typical research laboratory. Specialists in each step of the development process, from antigen selection, vaccine process development and manufacture, and preclinical animal modeling to clinical trials and assays of the immune response, contribute their expertise as the candidate moves along the development pathway. This allows multiple vaccine candidates to advance from concept to clinical trials efficiently and rapidly. Together, the Discovery sections and Vaccine Development Unit form a research and testing enterprise that can rapidly translate ideas into proof-of-concept trials, capture data about human immunity and responses to infection, which then inform new and improved strategies.
LMIV is the global leader in transmission-blocking vaccine development. Our leading TBV candidate, named Pfs230D1, is currently being tested in a phase 2 clinical trial evaluating safety and functional activity in malaria-endemic communities in Mali. Read about the ongoing community trial of Pfs230D1 in Mali, and the recent news release announcing our planned clinical trials of TBVs throughout West Africa, in collaboration with partners from the Netherlands, Denmark, Mali, Burkina Faso, Liberia, and Guinea.
For specific information on ongoing clinical trials, or to volunteer to enroll in a clinical trial, see the list of featured NIAID clinical trials.
Major Areas of Research
- Develop strategies for anti-infection, anti-disease, and transmission-blocking vaccines, including those that specifically protect pregnant women and their infants
- Conduct large longitudinal cohort studies to describe malaria epidemiology, especially in pregnant women and young children
- Execute human studies of natural or experimental controlled malaria infections to interrogate the host response and the characteristics of protective immunity
- Apply functional genomics tools including RNA sequencing and library screening platforms to identify targets of protective antibodies,
- Use structural biology, biochemistry, biophysics, immunology and microbiology approaches to enhance our basic understanding of malaria pathogenesis and host-parasite interactions in humans
- Engineer novel antigens that will lead to protection using structural vaccinology
- Develop assays, animal models, and perform preclinical trials that define the potential for protection
- Produce and formulate antigens suitable for human testing through quality control and quality assurance principles
- Assess vaccine platforms, nanoparticles, and adjuvant formulations to enhance vaccine immunogenicity and safety
- Execute clinical trials to test vaccines in the United States and in malaria-endemic areas
- Establish scientific collaborations and obtain outside funding to accelerate the program
See the published Annual Reports for each section of the LMIV by searching “Duffy, Patrick”, “Michal Fried”, or “Niraj Tolia” under Principal Investigator/Project Leader on the website.
The Laboratory of Malaria Immunology and Vaccinology includes the following principal investigators, staff scientists, and/or staff clinicians:
- Patrick E. Duffy, M.D.
- Michal Fried, Ph.D.
- Niraj Harish Tolia, Ph.D., FASTMH