Radboud University Medical Center, the Instituto de Medicina Molecular, and PATH's Malaria Vaccine Initiative will collaborate on first-in-human study of a novel malaria vaccine approach

Lisbon, Portugal, 30 May 2017—The Radboud University Medical Center (Radboudumc) in the Netherlands, the Instituto de Medicina Molecular Lisboa (iMM Lisboa) in Portugal, and PATH in Seattle, Washington announced today that they will collaborate to test a new approach to malaria vaccine development in humans for the first time.

The concept being tested is similar to that used by Edward Jenner to develop a vaccine against smallpox, the only disease affecting humans that has ever been eradicated. Jenner used cowpox—a similar but much less dangerous bovine version of the disease—to inoculate people against smallpox. In this clinical trial, based on data from earlier animal studies conducted by iMM Lisboa, the researchers will use a rodent version of the malaria-causing parasite (known as Plasmodium berghei) to determine if it can induce protection against infection by Plasmodium falciparum, the deadliest version of the parasite that infects humans.

In the study, a specific gene from P. falciparum known as the circumsporozoite protein (CS), will be inserted into the rodent parasite, resulting in a genetically modified version known as Pb(PfCS@UIS4). By inserting the gene for CS, the researchers hope to improve the potential of the modified rodent parasite to induce a protective response in healthy human volunteers.

"Bringing together the concept underlying the first vaccine ever developed, when Edward Jenner used the cowpox virus to immunize people against smallpox, with modern genetic manipulation tools, has resulted in a truly innovative approach to malaria vaccination," said Miguel Prudêncio, who is leading the research team at iMM Lisboa.

The trial will be conducted in two phases at Radboudumc in the Netherlands. In the first phase, 18 healthy adult volunteers will be recruited into three groups and exposed to varying, but carefully controlled number of bites from mosquitoes infected with the genetically modified P. berghei parasite. The researchers will closely monitor volunteers for signs of infection to make sure they are treated if they become ill. If all goes well in the Phase 1 study, volunteers from the highest dose group will enter the second phase of the study which is designed to assess protective efficacy of the approach.

"This is the first time we have tested a genetically modified malaria vaccine approach in Europe using this rodent parasite," said Robert Sauerwein, principal investigator and professor of medical parasitology at Radboudumc. "Along with our partners in the Netherlands, the Havenziekenhuis and Erasmus MC, we're looking forward to investigating whether this novel concept might one day contribute to the elimination and eradication of this terrible disease."

Malaria is a disease that killed more than 429,000 people in 2015, most of them young African children. Although the most advanced vaccine in development globally is slated for pilot implementation in parts of Africa beginning in 2018—an incredible accomplishment and critically important step—researchers are still on the hunt for a malaria vaccine that can confer higher levels of durable efficacy. The long-term goal of the malaria vaccine community, as outlined in the World Health Organization's Malaria Vaccine Technology Roadmap, is to develop vaccines with protective efficacy of at least 75 percent against clinical malaria, and vaccines that reduce transmission of the parasite in order to lower the incidence of malaria infection.

"Although much progress has been made to drive down the malaria burden with currently-available interventions, a highly effective vaccine would be an important new tool for malaria elimination," said Ashley Birkett, director of PATH's Malaria Vaccine Initiative (MVI). "We are pleased to collaborate with Radboudumc and iMM Lisboa on testing this novel approach."

With nearly two decades of experience in developing, managing, and overseeing human malaria challenge studies for vaccines against P. falciparum and P. vivax malaria, MVI, part of PATH's Center for Vaccine Innovation and Access, will provide financial support for the project, input into trial design, and oversight for the clinical studies. MVI also supported previous toxicology studies. Radboudumc, a leader in controlled human malaria infection with P. falciparum, will lead, implement, and conduct the study in the Netherlands. iMM Lisboa, a nonprofit research institute devoted to biomedical research, will collaborate with Radboudumc on the conduct of the clinical trial and will provide the vaccine candidate, Pb(PfCS@UIS4), for use.

• Katy Lenard, Burness | klenard@burness.com | +1 301 280 5719
• Pieter Lomans, Radboudumc | nieuws@radboudumc.nl | +31 6 3197 0558 or +31 6 5129 1446 (outside office hours)
• Ana de Barros, iMM Lisboa | imm-communication@medicina.ulisboa.pt | +351 217 999 411 x47335

PATH is the leader in global health innovation. An international nonprofit organization, PATH saves lives and improves health, especially among women and children. PATH accelerates innovation across five platforms—vaccines, drugs, diagnostics, devices, and system and service strategies and tools. By mobilizing partners around the world, PATH takes innovation to scale, working alongside countries primarily in Africa and Asia to tackle their greatest health needs. Learn more at www.path.org.

PATH's Malaria Vaccine Initiative (MVI) accelerates malaria vaccine development and catalyzes timely access in endemic countries, toward a world free from malaria. Standing at the intersection of malaria and immunization, MVI is part of PATH's Center for Malaria Control and Elimination and PATH's Center for Vaccine Innovation and Access. Learn more at www.malariavaccine.org.

Radboud University Medical Center is a leading academic center for patient care, education and research, with the mission 'to have a significant impact on healthcare'. Our activities help to improve healthcare and consequently the health of individuals and of society. We believe we can achieve that by providing excellent quality, participatory and personalized healthcare, operational excellence and by working together in sustainable networks. Learn more at https://www.radboudumc.nl/EN/Pages/default.aspx.

The iMM Lisboa – Instituto de Medicina Molecular is a leading Portuguese private non-profit research institute that offers a vibrant scientific environment, aiming to nurture innovative ideas in basic, clinical and translational biomedical research. Created in 2002, iMM Lisboa has established itself as a major national and internationally competitive biomedical institute. Its strategy has been defined by promotion of excellence, leveraged by high-quality human resources, increasing expenditure in infrastructures and knowledge transfer to the society. iMM Lisboa is an inclusive, equal opportunity employer offering attractive conditions and benefits. Learn more at: https://imm.medicina.ulisboa.pt/en/