Scientists Offer 2020 Vision of Vaccines for Malaria, TB & HIV/AIDS

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Collectively, malaria, TB & HIV/AIDS cause more than five million deaths per year – nearly the entire population of the state of Washington – and represent one of the world’s major public health challenges as we move into the second decade of the 21st century. In the May 26, 2011, edition of the premier scientific journal Nature, Seattle BioMed Director Alan Aderem, Ph.D., along with Rino Rappuoli, Ph.D., Global Head of Vaccines Research for Novartis Vaccines & Diagnostics, discuss recent advances in vaccine development, along with new tools including systems biology and structure-based antigen design that could lead to a deeper understanding of mechanisms of protection. This, in turn, will illuminate the path to rational vaccine development to lift the burden of the world’s most devastating infectious diseases.

According to Aderem, a systems biology pioneer who recently joined Seattle BioMed to incorporate that approach with the Institute’s infectious disease research, new conceptional and technological advances indicate that it will be possible to develop vaccines for the “big three” infectious diseases within the next 10 years. “Success will be largely dependent on our ability to use novel approaches such as systems biology to analyze data sets generated during proof-of-concept trials,” he explained. “This will lead to new insights such as the identification of correlates of protection or signatures of immunogenicity and the acceleration of large-scale clinical trials.” Aderem added that innovative, new clinical and regulatory approaches will also accelerate the pathway to much-needed vaccines.

The article discusses the strengths and criticisms of the systems biology approach, with the key strength of the approach lying in its ability to capture and integrate massive amounts of biological data to visualize emergent properties that are not demonstrated by their individual parts and cannot be predicted from the parts alone. “The power of systems biology comes from its capacity to predict the behavior of an entire biological system,” Aderem said. “From there, we can optimize vaccine candidates and predict whether a drug or vaccine candidate can work before it moves into large scale, very expensive clinical trials.”

Systems biology can also be used to speed the often lengthy clinical trial experience. Aderem and Rappuoli estimate that in trials of new vaccines for malaria, TB and HIV/AIDS, only one hypothesis has been tested every eight years in the past three decades. “We cannot afford this approach if we want to have an impact on disease in a reasonable timeframe,” Aderem said. “We can accelerate clinical development by performing more efficacy trials and by improving their design using systems biology approaches to test several hypotheses in parallel and having an adaptive design to expand the outcomes that prove most promising.”

Aderem and Rappuoli also debunk one of the key criticisms of systems biology – that it is overly reliant on computation. “Much of this comes from a misunderstanding on the role of computers in systems biology,” Aderem explained. “Computers are not expected to come up with biological insights from the outset, but are meant to facilitate an integration of discovery science with hypothesis-driven science to yield a holistic description of a biological system.”

While progress has been made over the past few years in the development of novel vaccines against the three most challenging infectious diseases in the world, Aderem and Rappuoli conclude that innovative design of clinical trials, testing several vaccines in parallel and getting early information using systems biology approaches will accelerate vaccine development and increase understanding of the human immune system.

Source: Seattle Biomedical Research Institute (Seattle BioMed)

New Biomarkers Study Could Lead to Improved Malaria Vaccines

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In the first study of its type in the malaria field, Seattle BioMed has been awarded an $8.9 million grant from the Bill & Melinda Gates Foundation to identify biomarkers that will allow malaria vaccine design based on robust predictors of protective immunity.

According to Ruobing Wang, M.D., Ph.D., 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, the company will call upon its areas of expertise and knowledge – 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. It will also begin full-scale trials in its Malaria Clinical Trials Center, and employ its newfound expertise in the area of systems biology.

Seattle BioMed scientists have developed genetically attenuated whole parasite vaccine strains that have proven successful in rodent malaria models and have moved into human studies. “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,” explained Seattle BioMed’s Stefan Kappe, Ph.D. “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.

Seattle BioMed researchers will employ 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 Alan Aderem, Ph.D., 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.

Wang is leading the study – Seattle BioMed’s first to include the integration of its recently announced systems biology approach to infectious disease research – 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).

Source: PR Newswire