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The Wistar Institute announces it has been awarded a $1,494,972 grant by the Bill & Melinda Gates Foundation to advance a DNA-based vaccine candidate for protection against malarial infection utilizing a synthetic DNA platform created in the lab of David B. Weiner, PhD, executive vice president, director of the Vaccine & Immunotherapy Center at the Wistar Institute and the W.W. Smith Charitable Trust Professor in Cancer Research.
Wistar will collaborate with Inovio Pharmaceuticals, Inc. and Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health on this research effort.
Currently, RTS,S (Mosquirix™) is the only malaria vaccine that has moved through phase III trials, delivering modest protection for the populations most at risk. The vaccine also requires four doses and decreases in effectiveness over time providing partial protection. This issue of durability of protection as well as limited group protection supports the need to develop second generation vaccine candidates.
Incorporating Weiner’s and collaborators’ more than 25 years of research in design and delivery of synthetic DNA vaccines, the team’s goal is to generate a new vaccine that drives robust antigen-specific antibody and T cell immune responses. The Weiner Lab helped to found the field of nucleic acid vaccines and was the first to move DNA vaccines to clinical studies, establishing their safety and immunogenicity and opening up the field of DNA vaccines for clinical development.
“DNA vaccines have a significant public health potential to rapidly impact emerging pandemics, as this technology has conceptual safety, development, speed of production, field stability, and deliverability advantages for vaccine and immunotherapy development,” said Weiner. “These synthetic DNA approaches can be developed for important infectious diseases, and with our collaborators, we have shown this consistently by rapidly engineering multiple synthetic DNA vaccines and advancing them to clinical study with positive outcomes of safety and immune potency.”
Funding from the Bill & Melinda Gates Foundation will enable this team to adapt the technology to produce a synthetic DNA vaccine encoding antigens of Plasmodium (P.) faliciparum, the micro-organism that causes malaria. This strategy instructs the vaccine recipient to produce the antigen in his/her own body so that the immune system can be activated and mount a rapid and potent response against malaria. Fidel Zavala, MD, professor in the Bloomberg School’s Department of Microbiology and Immunology and senior member of the Johns Hopkins Malaria Research Institute, will be responsible for testing the vaccine in animal models. Inovio Pharmaceuticals, Inc. will bring improved vaccine delivery and production know-how with their advanced CELLECTRA® electroporation delivery device that generates small, directional electric currents into the skin to facilitate optimal vaccine uptake, production of the antigen, and generation of relevant immune responses.
“We are excited to participate in this novel collaboration with the Wistar team, with the support of the Bill & Melinda Gates Foundation, focusing on synthetic DNA and Cellectra EP,” said Laurent Humeau, PhD, senior vice president of research & development at Inovio Pharmaceuticals, Inc. “The continued advancement of Cellectra Technology for synthetic DNA delivery, in this case against the malaria parasite, builds on our platform’s versatility, flexibility of design, ease of manufacturing, stability, reproducible clinical immune potency, and safety advantages compared to more traditional development platforms for vaccines.”
Malaria is a leading cause of death in infants and children in sub-Saharan Africa, including Malawi, Ghana and Kenya, as well as other developing areas of the world. A complex disease caused by a mosquito bite, the malaria parasite is able to evade the immune system and enter the bloodstream and eventually migrate to the liver where it establishes infection. There are four common strains of malaria, though P. falciparum is the most severe strain and is prevalent in Africa. A global disease burden, malaria accounted for 216 million cases worldwide and 445,000 deaths in 2016.
Source: The Wistar Institute