Seattle BioMed PIs Ruobing Wang and Alan Aderem
“If we have the ability to predict whether a vaccine candidate for malaria will work before it goes into large scale clinical trials, we could move away from today’s typical ‘trial and error’ method toward a more powerful predictive approach to vaccine discovery and development.”
-Alan Aderem, Ph.D.
After Seattle BioMed announced its bold plan to integrate a systems biology approach with its infectious disease research, malaria researchers wasted no time in incorporating this new method. In the first study of its type in the malaria field, Seattle BioMed researchers are identifying biomarkers that will allow malaria vaccine design based on robust predictors of protective immunity. The ability to predict is a hallmark of the systems biology approach.
With an $8.9 million grant from the Bill & Melinda Gates Foundation, Seattle BioMed’s Ruobing Wang, M.D., Ph.D., is leading the study with a team that includes Seattle BioMed’s Stefan Kappe, Ph.D., and Alan Aderem, Ph.D., along with Patrick Duffy, M.D., of the National Institutes of Health, Jonathan Derry, Ph.D., of Sage Bionetworks, and Xiaowu Liang, Ph.D., of Antigen Discovery Inc. (ADi). In August 2011, the project was touted by a scientific website as one of “21 scientific research projects starting this fall that could change the world,” citing the need for an effective vaccine to combat malaria.
Biomarkers Key to Vaccines
According to Wang, the goal of the study is to identify and validate biomarkers that correlate with vaccine-induced protective immunity against malaria infection. “In order to bring the burden of malaria under control – with the ultimate goal of eradicating the pathogens that cause disease – we know we need a highly efficacious anti- infection vaccine,” she explained. “But, without reliable biomarkers of anti-infection immunity, the development and testing of malaria vaccines is a slow and expensive process.” Biomarkers will be used for prediction and monitoring the vaccine efficacy in clinical trials and to select optimal vaccine candidates for development.
To conduct this research, Seattle BioMed is calling upon its proven areas of expertise and knowledge – successful vaccine and immunology studies in animal models of malaria, the ability to grow human malaria parasites in mosquitoes for research and clinical studies, and its ability to develop genetically attenuated parasite strains for human trials.
From Mice to Men (and Women)
Through Kappe’s research, Seattle BioMed scientists have developed genetically attenuated whole parasite (GAP) vaccine strains that have proven successful in rodent malaria models and have moved into human studies, which show the validity of the approach. “In this new study, we will use genetically attenuated parasite strains as probes to determine whether host correlates of immunity can be identified during vaccination in mice,” Kappe explained. “These model vaccines provide an opportunity to discriminate biomarkers associated with complete, long-lasting protection from those associated with partial, short-lived or lack of protection.”
Researchers at Seattle BioMed will then apply the knowledge gained in mouse models to human studies. “Through studies conducted at Seattle BioMed’s Malaria Clinical Trials Center, we’ll evaluate whether biomarkers of protection identified in the rodent models will predict protective immunity in humans,” explained Wang.
Fast Track to Vaccines
Applying Aderem’s expertise in the field of systems biology to malaria research will be a key component of this project. Seattle BioMed researchers are employing network analysis of transcriptional responses to predict protection in both mice and humans to determine if they can find universal markers that will allow them to optimize vaccine candidates. According to Aderem, the power of systems biology lies in its capacity to predict the behavior of a biological system. “If we have the ability to predict whether a vaccine candidate for malaria will work before it goes into large scale clinical trials, we could move away from today’s typical ‘trial and error’ method toward a more powerful predictive approach to vaccine discovery and development,” he said.
Through these integrated studies,
Seattle BioMed researchers will deliver
a set of candidate immune biomarkers associated with protection against malaria infection that can be used for monitoring vaccine efficacy. “This will facilitate future malaria vaccine trials with the ultimate goal of accelerating the development
of a highly effective malaria vaccine
that has the potential to save millions
of lives,” said Wang.