Breakthroughs Blog: Research Roundup

A Phase 1 clinical trial testing a candidate that could become the first vaccine for leishmaniasis, a disfiguring skin disease, is set to begin soon in Kenya and Brazil, where the disease in endemic, as well as in Cincinnati, Ohio, as the disease risk grows in the United States. The Global Health Innovative Technology (GHIT) Fund is supporting the trial, which will test the safety and immune response of the candidate in healthy people. The vaccine, which was developed using CRISPR gene-editing technology to mutate the parasite that causes the disease, previously demonstrated strong results in mice and has received US Food and Drug Administration approval as an investigational new drug, which allows the product to be tested in humans. The Coalition for Epidemic Preparedness Innovations (CEPI) has announced that it is providing funding to fast-track the development of three Ebola Bundibugyo virus vaccine candidates, as the concerning outbreak of the Bundibugyo strain, for which there are no approved vaccines, continues to grow in the Democratic Republic of the Congo and Uganda. Specifically, the funding will support preclinical development and Phase 1 clinical testing of Moderna’s mRNA vaccine candidate; help accomplish a key early step in vaccine manufacturing for IAVI’s vaccine, which is based on the organization’s rVSV vaccine platform; and help the University of Oxford prepare for a Phase 1 trial of its vaccine, which is based on the same platform as its Oxford/AstraZeneca COVID-19 vaccine.  Last week, Zendal announced the launch of the international MTBVAC AVANTE consortium to accelerate clinical development and prepare regulatory and policy pathways to ensure broad and equitable access of the MTBVAC tuberculosis (TB) vaccine candidate over the next four years. The current TB vaccine is more than 100 years old and offers inconsistent protection in adults against pulmonary TB, so a new and improved vaccine that is safe and effective across diverse populations who face TB risk will be essential to ending the pandemic. With funding from the Global Health EDCTP3, the consortium of 12 European and African partners will initially support two major ongoing trials in high-TB regions in sub-Saharan Africa, one evaluating the vaccine in adolescents and adults and one comparing the candidate’s protection in newborns to the existing vaccine.  

Amid the ongoing outbreak of the Bundibugyo strain of Ebola—for which there are no specific approved vaccines or therapies—in the Democratic Republic of the Congo and Uganda, the World Health Organization (WHO) has collaborated with outside experts to identify priority Ebola treatments and vaccines for clinical trials. On the treatment side, WHO recommended prioritizing Mapp Biopharmaceutical’s MBP134, Regeneron’s maftivimab, and Gilead Sciences’ antiviral remdesivir. For prevention, Gilead's experimental oral antiviral obeldesivir was highlighted as a priority for post-exposure use in contacts of confirmed cases. IAVI’s rVSV Bundibugyo was identified as the most promising vaccine candidate, but Oxford University and the Serum Institute of India’s ChAdOx1 Bundibugyo vaccine candidate could be available for testing sooner following additional animal testing. WHO is now working with authorities in Congo and Uganda and other partners to design and implement ethical clinical trials during the outbreak. An experimental drug for chronic hepatitis B could potentially serve as a functional cure for the virus, as demonstrated in recently published results from two international studies. For many, hepatitis B only causes short-term illness, but for some, it can become a chronic infection, gradually damaging the liver and, without treatment, leading to liver cancer, liver failure, or even death—it causes around 1.1 million deaths globally each year. Chronic infection requires lifelong therapy in the form of daily pills to reduce viral levels and prevent liver damage, which can be hard to adhere to or access in some countries. Bepirovirsen, developed by GSK and Ionis Pharmaceuticals, was able to reduce the virus in around one in five patients to levels low enough for the immune system to keep it under control without treatment. The drug is under fast-track review by the US Food and Drug Administration, which is expected to make a decision later this year, and is also being considered by international regulators in Japan, China, and Europe. A research team at Georgia State University has developed a promising antiviral drug candidate that could help treat measles, croup, and related viral diseases that cause contagious and life-threatening respiratory infections, as falling coverage of the vaccine for measles, mumps, and rubella raises the risk of infection. The drug, GHP-88310, was designed to be a once-a-day oral pill for vulnerable patent groups, like children and immunocompromised patients, which make up the majority of croup and measles cases. GHP-88310 has been shown to be well-tolerated in rats, mice, ferrets, and dogs at higher concentrations. 

Last week, SC Johnson; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and the US Department of State announced a new agreement to accelerate access to an innovative malaria vector control tool in high-burden countries. This marks the second such partnership between the State Department, the Global Fund, and a US company to expand global access to new products under the department’s global health strategy, after one with Gilead for lenacapavir for HIV prevention. This initiative will scale up the SC Johnson Guardian™ spatial repellant tool, a small mesh fabric sealed inside a pouch that is hung indoors, releasing an active ingredient that repels mosquitoes for up to a year. The tool was recommended by the World Health Organization last year, the first new category of vector control products to be recommended in 25 years. The partners aim to reach 60 million people across ten-high burden countries with 30 million products over three years, with manufacturing based in Nairobi, Kenya. A new observational study found that even with only moderate levels of malaria vaccine coverage achieved, the initial introduction of the RTS,S/AS01 malaria vaccine in high-burden African countries has contributed to a significant reduction in deaths among children. Specifically, despite only moderate uptake of three doses and low uptake of the fourth, the vaccine was found to have saved the lives of one in eight eligible children in the first three African countries to offer the vaccine from 2019-2023, which represents a 13.2 percent reduction in death. These results add to the evidence supporting continued scale-up of RTS,S—one of two malaria vaccines now included in national immunization schedules in 25 sub-Saharan African countries—and underscore the promise of continued investment in developing new and improved malaria vaccines. Nonprofit Caring Cross has shared an early copy of data showing that, in a small study, a single infusion of engineered immune cells suppressed HIV long term in several patients, offering proof-of-concept for a single-shot functional cure. The approach, adapted from cancer research, involves extracting immune cells from participants living with HIV, engineering the cells to carry molecules that simultaneously kill infected cells and prevent the immune cells from becoming infected, and injecting them back into participants. HIV is notoriously hard to control because the virus persists in hard-to-eliminate latent reservoirs, requiring lifelong ongoing treatment to suppress the virus.  This research could pave the way for the development of a single, low-cost intervention that could sustain viral suppression without the need for regular therapy. The research, which is still in the very early stages, is scheduled to be presented at an upcoming scientific conference. 

A team of researchers from the United Kingdom, the United States, and South Africa is developing a vaccine for hantavirus, the virus behind a worrying outbreak on a cruise ship in the Atlantic Ocean. Hantavirus is typically spread by rodents, and transmission between humans is very rare. There is no specific treatment of vaccine for hantavirus, which, as seen in the current outbreak, can be deadly. The researchers are using an innovative method called insilication to make the vaccine thermally stable, aiming to reduce the high resource and economic costs of meeting the cold chain and storage requirements that are associated with many vaccines. Moderna’s mRNA-based seasonal flu vaccine outperformed conventional flu shots in a late-stage international trial of more than 40,000 adults aged 50 and older. The US Food and Drug Administration is currently reviewing the vaccine after rejecting the initial application and is expected to make a decision by August 5. If approved, the vaccine would be the first mRNA seasonal flu shut in the United States. mRNA vaccines can be produced much more quickly than conventional flu shots, which could enable public health authorities to wait longer before choosing which flu strains to target, giving them more time to gather up-to-date data about circulating strains before flu season begins. A research team has discovered a previously unknown mechanism by which HIV-1 can infect resting cells, challenging previous assumptions and raising new possibilities for the development of improved treatments. For HIV to infect immune cells, it must deliver its genetic material into the cell’s nucleus, which is surrounded by a protective structure—how the virus has broken through the barrier has long puzzled scientists. Another obstacle to an HIV cure has been the latent reservoir of resting immune cells that house dormant virus, which cannot be cleared by treatment. The researchers found that when the virus spreads between immune cells, it triggers a signal that unlocks this protective gateway around the nucleus, allowing the virus to enter. They also found that this process does not require the immune cell to be activated, meaning that the reservoir can be established and maintained while cells are resting, upending long-standing assumptions and unlocking new avenues toward the development of a treatment that can destroy the virus and target the latent reservoir.