DSM-265

A three-dose regimen of a whole-parasite vaccine against malaria -- called Plasmodium falciparum sporozoite (PfSPZ) vaccine -- demonstrated safety and efficacy when tested in adults living in Burkina Faso, West Africa, which has endemic malaria. A three-dose regimen of a whole-parasite vaccine against malaria -- called Plasmodium falciparum sporozoite (PfSPZ) vaccine -- demonstrated safety and efficacy when tested in adults living in Burkina Faso, West Africa, which has endemic malaria. That is the finding of a new study published on Dec. 7, 2022, in Science Translational Medicine. Researchers at the University of Maryland School of Medicine's Center for Vaccine Development and Global Health (CVD) led the work. About 241 million people worldwide were infected with malaria in 2020, and 627,000 people died from their infections. Scientists have tried for decades to develop a highly effective malaria vaccine without much success. That is because the vaccines have been shown not to provide much protection in those who have already been infected with malaria earlier in life due to their acquired immunity. The first vaccine against malaria (RTS,S/AS01) was approved by the World Health Organization in October 2021, and it provides modest protection against malaria. The new study involved 80 participants in a randomized controlled clinical trial comparing three doses of the PfSPZ vaccine against a placebo. At six months follow up, vaccine efficacy was up to 48 percent; at 18 months follow up, vaccine efficacy was up to 46 percent. "Our study shows that the vaccine can be given to malaria-experienced adults in a highly endemic area and still provide protection, which is difficult and complicated as these individuals already have significant immune responses to malaria parasites that must be overcome by a vaccine for it to be successful," said study corresponding author Matthew B. Laurens, MD, MPH, Professor of Pediatrics at UMSOM and Director, International Clinical Trials Unit in the Malaria Research Group at CVD. PfSPZ Vaccine is made with a live-attenuated form of the malaria parasite Plasmodium falciparum sporozoite, which is transmitted by mosquitos. The vaccine is made by Rockville, Maryland-based Sanaria Inc. and has been shown to provide at least 90-percent protection in challenge studies where volunteers are infected with malaria (in a highly controlled way); these studies were conducted by CVD researchers in the U.S. and by other groups in Tanzania. In African adults who previously had malaria, PfSPZ provided 52 percent vaccine efficacy against naturally transmitted malaria infection. Protection lasted 8 to 14 months. In the new study, researchers wanted to reduce the number of required injections from five shots to three, while improving vaccine efficacy. They assessed safety, tolerability, immunogencity, and vaccine efficacy of three injections of the vaccine in a two-part study. The first part enrolled 32 adults in a dose-escalation phase in 2016 and the second enrolled 80 adults in a randomized trial in 2017. In the randomized trial, 39 received PfSPZ Vaccine and 41 received placebo. Study participants were healthy men and non-pregnant women ages 21 to 40. The vaccines were well tolerated and without concerning side effects. "New strategies are needed to achieve the United Nations sustainable development goal of a 90-percent reduction in malaria incidence and mortality by 2030," said UMSOM DeanMark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. "Innovative vaccines that provide a higher level of protection against malaria are urgently needed to help to achieve this goal." Additional co-authors on the newly published research from UMSOM's Center for Vaccine Development and Global Health include: Kirsten E. Lyke, MD, Professor of Medicine; Sudhaunshu Joshi, MS, Laboratory Specialist; Biraj Shrestha, Laboratory Assistant; and Kathy Strauss, Laboratory Specialis. The new study reflects a long history of malaria vaccine development at UMSOM that started in the early 1970s with landmark research from David Clyde, MD, former head of malarial studies at CVD. His studies demonstrated that high-level protection against malaria infection is possible using a whole organism vaccine. Future research includes conducting additional clinical trials of the PfSPZ Vaccine in groups that would benefit most from vaccine-induced protection, including children, travelers, military personnel, and pregnant women. Many of these studies are underway, including an ongoing trial at UMSOM to administer a compressed schedule of three doses of PfSPZ Vaccine in one month, which is a feasible timeline for travelers and military populations. Results of this study are expected in 2023. The study was funded by NIH's National Institute of Allergy and Infectious Diseases grants U01AI112367 and 5R44AI055229.

Scientists report a new way to test vaccines that may be as rigorous and stringent as exposure to field strains of malaria. Malaria is the deadliest mosquito-borne parasitic infection of humans. In 2021, after a century of research, the World Health Organization (WHO) approved the world's first malaria vaccine. That vaccine reduces the incidence of malaria infections in young children aged 5-17 months by only 30 percent, meaning that it remains critical to continue developing and testing more effective vaccines. WHO's goal is to find a vaccine that prevents infection as well as cases of severe malaria. However, testing vaccines in the field is challenging and requires large number of volunteers and long periods of follow-up. This process increases the expense and reduces the number of trials that researchers can perform. Now, scientists at the University of Maryland School of Medicine's (UMSOM) Institute for Genome Sciences (IGS) and the UMSOM Center for Vaccine Development and Global Health (CVD), and their collaborators report a new way to test vaccines that may be as rigorous and stringent as exposure to field strains of malaria. Their study was published in the June issue of Nature Communications. Their method has two key aspects. First, they expose vaccinated volunteers to malaria in a controlled clinical environment. Secondly, for this testing, they use a strain of malaria that is genetically very different from the one used in the vaccine, as well as from strains in the geographic region to which the vaccine is intended. This technique allows scientists to test how well the vaccine works in small numbers of volunteers under controlled settings and in a rapid fashion and predicts how well the vaccine may perform in the field. This lets researchers select the best vaccines for larger studies in the field. This method will increase the efficiency of vaccine testing and should accelerate malaria vaccine development. "The standard for many investigators has been to test vaccines with a strain similar to the one used in the vaccine's development," explained the study's lead author, Joana Carneiro da Silva, PhD, Professor of Microbiology and Immunology at UMSOM and IGS. "Using a strain that is both genetically distant from the one in the vaccine -- as well as from the strains circulating in the area where malaria is rampant and the vaccine will be used- is a more stringent way to test vaccine effectiveness." Researchers are studying the effectiveness of a vaccine (PfSPZ Vaccine) made by the company Sanaria, Inc, based in Rockville, Maryland. This vaccine uses the West African parasite strain known as PfNF54. One objective is to use this vaccine to protect individuals with little or no previous exposure to malaria, including those living or traveling in Africa. The long-term goal is to use the vaccine in mass vaccination programs to eliminate malaria from specific regions in Africa. For the study, researchers infected mosquitoes with a Brazilian malarial strain and then exposed U.S. volunteers who had been vaccinated with the Sanaria vaccine (as well as those who received a placebo) to the bites of infected mosquitos in a controlled clinical setting. They also vaccinated research participants in Mali with the same dose of the vaccine to compare observed vaccine efficacy in the field with that in the clinic. Through genomic sequencing, researchers had shown that the Brazilian strain differed greatly from 700 strains previously collected from across Africa, including the one used to make the vaccine. The researchers looked at about 200 volunteers in four trials -- two in the United States and two in Mali. In all four, they observed how many people became infected with malaria, as well as how long it took for them to become infected, comparing clinic to field. At the end of six months, they found the vaccine was just as effective in both populations. In addition, previous comparisons had shown that those volunteers who had never been exposed to malaria developed more antibodies than those in the field, proving that it would work well in first-time travelers to the area. The research team included scientists from Sanaria Inc.; the Naval Medical Research Center; University of Tübingen in Germany; the Malaria Research and Training Center in Bamako, Mali; and the Laboratory of Malaria Immunology and Vaccinology at NIAID, NIH. The World Health Organization estimates that in 2020, 241 million cases and 627,000 deaths worldwide were due to malaria, including 2,000 cases diagnosed in the United States from travelers and immigrants who were exposed elsewhere. The variety of malarial strains globally makes vaccine development particularly difficult. "Given the diversity of malaria strains worldwide, this research demonstrates that the Brazilian strain is as diverse as any strain detected in Africa," said Kirsten E. Lyke, MD, Professor of Medicine and Director of the Malaria Vaccine and Challenge Unit at the CVD and an author of the paper. Dr. da Silva noted this new model can be used in the future in selecting challenge strains to test the efficacy of vaccines against other parasitic diseases, using carefully controlled clinical settings to compare against field studies. This study was funded the National Institutes of Health's National Institute of Allergy and Infectious Diseases intramural program and grants (U19AI110820, R01AI141900, 5R44AI058375-10, and 5R44AI055229-11) , and the Department of Defense (W81XWH1420011).