The Global Health Innovative Technology Fund has awarded the University of Florida and partners in the United States and Japan $3.2 million to advance a promising vaccine to prevent transmission of malaria.
Rhoel Dinglasan – an associate professor of infectious diseases in UF’s College of Veterinary Medicine and the university’s Emerging Pathogens Institute – has spent years developing a malaria transmission blocking vaccine, or TBV. The blood mosquitoes get from immunized humans would prevents prevent the insects from becoming infected by the Plasmodium parasite that causes malaria, thus breaking the cycle of disease transmission.
Female Anopheles mosquitoes pick up the Plasmodium parasite when they bite an infected human, then spread the parasite when they bite other people.
After Dinglasan and his colleagues identified a protein in the mosquito gut that Plasmodium needs to infect the Anopheles mosquito, called alanyl aminopeptidase N, or AnAPN1, they saw a path to preventing transmission of the disease by creating a vaccine to generate antibodies to AnAPN1 in humans.
Initial vaccine testing in mice stalled because the animals primarily generated antibodies to a less-crucial fragment of AnAPN1, so Dinglasan and his team refocused their efforts on solving the structure of the protein, which allowed them to more precisely map the relevant transmission-blocking regions of the protein to target. When they tested the antibodies to the redesigned vaccine target using infected blood samples from children in Cameroon, a country hard hit by malaria, they found that minute amounts of the antibody completely prevented transmission of the parasite to the mosquito.
The new grant from the Global Health Innovative Technology, or GHIT, Fund will further development of processes to move the vaccine from the experimental stage to human trials and, ultimately, a clinical treatment. The GHIT Fund is an international public-private partnership spearheaded by the Government of Japan, the Bill and Melinda Gates Foundation, Wellcome Trust and a group of pharmaceutical companies.
“AnAPN1 is a great pan-malaria transmission-blocking vaccine and we have made it even better,” said Dinglasan, who was recruited to Gainesville under the UF Preeminence initiative. “This funding support puts the vaccine back in the process development and vaccine production pipeline with an eye on getting to first-in-human trials in a few more years.”
Historically, malaria prevention has focused on killing the mosquitoes that transmit the disease using pesticides like DDT or shielding humans from mosquitoes with nets, but these approaches alone are not enough to prevent nearly a half-million people around the world from dying from malaria annually, many of them children under 5.
The next phase of the project involves numerous partners contributing unique capabilities.
CellFree Sciences of Japan is developing the important control antigens and Hamamatsu Pharma Research of Japan will assess the long-term potency of the vaccine in non-human primates.
The Infectious Disease Research Institute, or IDRI, of Seattle, has been a long-time longtime partner on this project and continues to assist by providing the adjuvant to boost the immune response to the antigen.
Ology Bioservices, a UF spinoff operating out of the university’s Sid Martin Biotech Incubator, will develop the large-scale, process development and manufacturing plan and supply the AnAPN1 vaccine candidate for use in ongoing pre-clinical studies and to prepare for subsequent clinical testing.
Centre Pasteur du Cameroun will test the efficacy of antibodies generated in response to AnAPN1 in mice and non-human primates against naturally circulating strains of the malaria parasite, Plasmodium falciparum, in direct membrane feeding assays in Cameroon.
Dinglasan said the TBV would work in concert with a traditional vaccine being developed by GlaxoSmithKline called Mosquirix™, which is scheduled for pilot implementation in three African countries this year.
“Our vaccine should work against all five Plasmodium parasite species that affect human health,” he said. “Mosquirix™ does not achieve full protection and many people, mostly kids, will still be infectious to the mosquito. Our vaccine puts a stop to that.”
Ultimately, Dinglasan hopes the TBV will be the final nail in the malaria coffin, eliminating pockets of residual malaria transmission that prevention efforts and traditional vaccines cannot reach.
“This vaccine can help stamp out malaria globally,” he said.
About CellFree Sciences
CellFree Sciences (CFS) provides comprehensive solutions for protein production and analysis using the ENDEXT® Technology Platform originally developed in the laboratory of Prof. Yaeta Endo at Ehime University in Japan. With our different WEPRO® wheat germ protein expression extracts, CFS is serving the research community with protein synthesis services, reagents, and the fully automated Protemist® robotic protein production systems.
About Hamamatsu Pharma Research
Hamamatsu Pharma Research (HPR) is a preclinical CRO specializing in efficacy testing of novel therapeutics in nonhuman primate disease models. Our services provide preclinical proof of concept data that facilitates go/no-go decision making for new drug development.
About Ology Bioservices, Inc.
Ology Bioservices, Inc. (formerly Nanotherapeutics, Inc.) is a biologics-focused contract development and manufacturing organization (CDMO) serving both government and commercial clients. The Company’s capabilities include a pilot facility for performing optimization of upstream, downstream and formulation functions, bulk cGMP manufacturing and analytical development for proteins, antibodies, viral vaccines and gene therapy drug products.
As a nonprofit global health organization, IDRI (Infectious Disease Research Institute) takes a comprehensive approach to combat infectious diseases, combining the high-quality science of a research organization with the product development capabilities of a biotech company to create new diagnostics, drugs and vaccines. Founded in 1993, IDRI has 125 employees headquartered in Seattle with nearly 100 partners/collaborators around the world.
The Centre Pasteur du Cameroun (CPC) founded in 1959, is a state-owned public health and biomedical research institute located in Yaoundé, the capital city of Cameroon. CPC is a WHO regional reference center for several infectious diseases, and member of the Institut Pasteur International Network with headquarters in Paris, France. The main activities of the CPC include service, public health, training and research. Research is centered on bacterial, viral and parasitic agents, and their respective major pathologies such as HIV/AIDS, tuberculosis, viral hepatitis, malaria, dengue and other vector-borne diseases as well as neglected tropical diseases.
University of Florida plant biologist Pam Soltis will receive the Southeastern Universities Research Association’s 2018 Distinguished Scientist Award, given annually to a scientist whose extraordinary work fulfills the association’s mission to “advance collaborative research and strengthen the scientific capabilities of its members and the nation.”
Soltis, a distinguished professor and curator at the Florida Museum of Natural History at UF, will be presented with the award and its $5,000 honorarium at the SURA Board of Trustees meeting at the Thomas Jefferson National Accelerator Facility in Newport News, Virginia, on April 26.
A member of the National Academy of Sciences and the American Academy of Arts and Sciences, Soltis studies plant diversity, with emphasis on the origin and evolution of flowering plants, plant genome evolution and conservation genetics. She uses genomic methods, natural history collections and computational modeling to understand patterns and processes of plant evolution and identify conservation priorities.
To help increase the public’s understanding of biodiversity, she joined an interdisciplinary team to create multimedia art pieces and an animated film that use the “Tree of Life” as a metaphor for how all living things are related to one another.
In nominating Soltis for the award, UF Vice President for Research David P. Norton wrote that her work in genetics and genomics was not only groundbreaking for plant scientists but for all scientists who want to understand the genetic relationships between populations and species.
“Dr. Soltis’ research has dramatically changed our understanding of the natural world,” Norton said. “Her work uncovers new relationships in the Tree of Life, illuminates fundamental aspects of plant biology, points to areas of greatest conservation concern and continually pushes the boundaries of what is possible in bioinformatics. In addition to being a world-class researcher, Dr. Soltis also shows a tremendous commitment to training and mentoring the next generation of scientists and engaging the minds and imagination of the public. UF is very fortunate to have such a leader.”
SURA Board of Trustees Chair Kelvin Droegemeier, who is also vice president for research at the University of Oklahoma, said, “Dr. Soltis is the kind of researcher every university hopes to have on its faculty. She is a renowned scholar cited in respected journals, an aggressive researcher winning multiple grants and a passionate teacher impacting scores of students.”
Soltis has won numerous honors for her contributions to the study of plant diversity. Jointly with Doug Soltis, she received the Darwin-Wallace Medal from the Linnean Society of London, the R. Dahlgren International Prize in Botany, the Asa Gray Award from the American Society of Plant Taxonomists, the Botanical Society of America’s Merit Award and the Stebbins Medal from the International Association of Plant Taxonomists. Thomson Reuters named her one of the World’s Most Influential Scientific Minds in 2014. She also won the Botanical Society of America’s Centennial Award.
Soltis earned a bachelor’s degree in biology from Central College and a doctorate degree in botany from the University of Kansas. She joined UF in 2000, after serving on the faculty of Washington State University for 14 years.
She is the founding director of the UF Biodiversity Institute and a member of the UF Genetics Institute.
She has published more than 400 peer-reviewed journal articles and oversees a diverse lab of more than a dozen graduate students and postdoctoral fellows and routinely trains at least five undergraduate students per semester.
Soltis has received more than $37 million in support for her research on the evolutionary history and genomics of flowering plants. She became the lead investigator on the project that launched the new Genetic Resources Repository at the Florida Museum and is one of the principal investigators for iDigBio, a project that made UF the hub for the NSF-funded program to digitize the collections of all U.S. natural history museums. This led to a $27-million award that has brought widespread recognition to UF for its leadership role in bioinformatics. She is also a co-principal investigator of a $7-million Department of Energy project to pinpoint the genes that allow certain plants to fix nitrogen and engineer this genetic pathway into other plants for food and fuel.
“I am very honored to receive this award,” Soltis said. “I have a fantastic group of collaborators at UF and elsewhere, and this award is for all of them as well. I’m also thankful for the supportive environment at UF, where collaboration is both valued and encouraged.”
SURA is a nonprofit consortium of more than 60 research institutions in the southern U.S. and the District of Columbia.
The SURA Distinguished Scientist Award was established in 2007, commemorating the organization’s 25th anniversary. SURA’s development & relations committee manages the solicitation, screening and selection of the recipient from a SURA member institution. The president and trustee of each of SURA’s member research universities are eligible to make one nomination for the Distinguished Scientist Award.
Soltis joins UF College of Pharmacy Dean Julie Johnson, who received the award in 2015, and microbiology Distinguished Professor Lonnie Ingram, who was recognized in 2008.