Photo: Anopheles stephensi mosquito, a known vector of malaria
Thanks to a new multimillion dollar grant from the National Institutes of Health, Dr. Kent Weinhold, Professor and Chief, Division of Surgical Sciences, and Dr. Emmanuel Walter, Department of Pediatrics, will lead efforts to evaluate the immunogenicity and efficacy of a novel malaria vaccine as part of the Vaccine Trials Evaluation Unit (VTEU) at Duke.
Led by Dr. Weinhold, Duke Surgery’s Immune Profiling Core (DIPC) will assess the cellular immune responses of volunteers in an upcoming malaria vaccine trial through the VTEU. A licensed malaria vaccine remains elusive because so far no vaccine has induced a clinically beneficial immune response in recipients.
“Malaria vaccines to date have proven to be kind of a disappointment,” says Dr. Weinhold. “The highest efficacy in the last trial reported in the New England Journal of Medicine was less than 20% so there’s a lot of room for improvement.”
According to the World Health Organization, 214 million cases of malaria and 438,000 deaths from malaria occurred in 2015. Children under the age of 5 who are more immunologically susceptible than adults represent 70% of all malaria deaths. Malaria is caused by five different species of the Plasmodium genus, a parasite transmitted by Anopheles mosquitoes.
Current malaria vaccines target antigens that elicit immune responses to disrupt the parasite life cycle or destroy infected cells in the body. However, parasite drug resistance poses a significant challenge to the development of a highly efficacious vaccine. A key goal of this award is to optimize assays for measuring specificity against malaria parasites, including the selection of antigens that will be most appropriate to include in a vaccine.
The Group Health Research Institute in Seattle, Washington will conduct the 20-month trial with a total of 28 healthy volunteers, 18-50 years of age. In this unusual trial design, volunteers will receive the vaccine through hundreds of bites from mosquitoes infected with a genetically attenuated parasite (GAP) that does not cause disease. To determine whether the GAP vaccine prevents infection, the volunteers will then undergo controlled human malaria infection (CHMI), a safe and well-established model for testing the efficacy of malaria vaccines.
“This vaccine trial is unique because it has a malaria challenge with it so volunteers will be sticking their arms in places with malaria-infected mosquitos to see if they get infected,” says Dr. Weinhold.
Dr. Weinhold’s team will monitor the levels of T and B cells and circulating cytokines in volunteers using flow-based platforms, such as intracellular cytokine staining. By measuring these immune responses, the team aims to determine the safety, efficacy, and immunogenicity of the candidate vaccine.
Building New Capabilities
This new funding will also enable the DIPC to monitor immune responses to novel, first-in-human vaccines against newly emerging pathogens that have migrated to the Western hemisphere and are now appearing in the Caribbean and southern United States. These emerging infectious diseases include avian influenza, West Nile Virus, chikungunya virus, and dengue virus. Additionally, future trials may assess candidate vaccines to combat the global threat of the Zika virus.
“This award creates the infrastructure for identifying efficacious vaccine strategies for developing pathogens. With this funding, we hope to make vaccines better and better over time,” says Dr. Weinhold.
As part of their capacity-building efforts, the DIPC will acquire a Becton Dickinson FACSymphony™ A5 flow cytometer. This highly sensitive instrument, just released in 2016, can perform up to 50-parameter flow cytometric analyses, essentially taking “immunological snapshots” of patient samples. This cutting-edge technology uses a lower number of cells per sample, which reduces the need for large-volume samples.
The addition of this next-generation technology to the DIPC’s immune profiling repertoire will greatly enhance ongoing multidisciplinary collaborations at Duke. The DIPC is now working to identity immune signatures that predict clinical outcomes of neoplastic, pulmonary, autoimmune, and infectious diseases, as well as treatment responses to novel cancer immunotherapies. In addition, efforts are underway to pinpoint the immune markers of cognitive decline following surgery and ischemia– reperfusion injury following transplantation.
About the VTEU
The Duke VTEU is one of eight other VTEUs in the United States funded by the National Institute of Allergy and Infectious Diseases. Clinical activities under the Duke VTEU are coordinated through the Duke Clinical Research Institute, while international clinical trials are coordinated through FHI360, the Duke Global Health Institute, and the Naval Medical Research Center. The VTEU is administered by the Duke Human Vaccine Institute and includes collaborations with the Department of Pediatrics, the Department of Obstetrics and Gynecology, and the Department of Surgery.