Breakthroughs Blog: Research Roundup

Newly published data shows that the antiviral compound mosnodenvir, developed by Johnson & Johnson, is effective at preventing dengue infection in people deliberately exposed to the virus, which affects millions around the world every year. There are no approved treatments for dengue, and available vaccines face production and efficacy issues. Despite its promise, the future development of the drug is in flux after Johnson & Johnson halted all its infectious disease work last year. Negotiations are underway to find another company to advance the drug, which, if it continues to demonstrate potential, could be used to protect large populations during epidemics, as well as to protect people traveling to endemic areas. Last week, Brazil’s regulatory agency approved the Butantan Institute’s Butantan-DV vaccine for dengue for people aged 12 to 59. The vaccine demonstrated high efficacy in clinical trials against dengue, which causes millions of cases globally, with a substantial burden faced by Brazil. The single-dose vaccine could offer faster and simpler vaccination campaigns compared to existing vaccines. Brazil signed an agreement with WuXi Biologics to deliver approximately 30 million doses of the vaccine in the second half of next year. The results of a human-challenge Phase 2a trial published last week found that an mRNA vaccine was more effective against symptomatic and febrile flu compared to the conventional vaccine. Another trial published last week also found that mRNA flu vaccines were more effective than conventional vaccines. Beyond effectiveness, mRNA vaccines can also be made more quickly, helping ensure that vaccines match circulating flu strains. Additional studies that include older people, those with coexisting illnesses, and school-age children, who face elevated risks, will be required to ensure broad efficacy across populations. 

At the recent Union World Conference on Lung Health, TB Alliance presented the results of a Phase 2 clinical trial showing that the novel antibiotic candidate sorfequiline has the potential to improve tuberculosis (TB) treatment when combined with pretomanid and linezolid in people with drug-sensitive TB. The regimen was more effective than the current standard of care, and sorfequiline also demonstrated greater activity than bedaquiline, a key component of the BPaL regimen, a previous breakthrough that drastically reduced treatment time for most drug-resistant TB. This new treatment could shorten TB therapy even further. TB Alliance is working with partners ahead of the launch of a Phase 3 trial next year. Researchers at the University of California San Diego and partners have developed a new method to combat antibiotic-resistant bacteria, which could pave the way for developing alternatives to traditional antibiotics for treating a wide range of deadly infections, as the global threat of antimicrobial resistance continues to grow. The researchers used bacteriophages (or phages), which are viruses that infect and kill bacteria. Phages have been used to treat bacterial infections for more than 100 years but are usually limited in the bacterial strains they can successfully target. Researchers overcame this by allowing the pages to evolve alongside bacteria in a controlled laboratory setting for 30 days, enabling the phages to adapt their bacterial defenses, becoming more effective at killing a wide variety of bacterial strains, including drug-resistant ones, and better at suppressing bacterial growth for extended periods. Researchers at Indiana University have developed a molecular test that can simultaneously detect three dangerous fungi much faster than traditional methods, helping patients receive accurate, timely treatment against this growing global challenge. The test works by targeting genetic regions unique to each fungus, and it was much faster and more accurate than standard methods, a key advance as fungal infections are often mistaken for other respiratory illnesses. While the test still needs to be clinically validated in further studies, the research team believe it could eventually fill a major gap in fungal diagnostics. 

A Phase 1 randomized controlled trial found that a single dose of the ChAdox1 Rift Valley fever (RVF) vaccine was safe, tolerable, and elicited a strong immune response in 30 adults in Uganda, where RVF—a neglected, mosquito-borne disease that is considered a significant public health threat and a priority for vaccine development—is endemic. The trial was led by researchers at the Uganda Research Institute and the London School of Hygiene and Tropical Medicine Research Unit in Uganda and provides the first evidence supporting the vaccine from a trial in an endemic setting. While the vaccine could potentially be transformative for RVF prevention, further research is needed that follows participants for a longer period and includes a larger group of participants, including children, pregnant women, and immunocompromised people. Last week at the American Society of Tropical Medicine and Hygiene annual meeting, Medicines for Malaria Venture and Novartis shared the results of a Phase 3 study testing a new malaria treatment, known as GanLum, finding that the treatment was highly effective at treating malaria, including drug-resistant cases, and could also block disease transmission. GanLum was found to be 99.2 percent effective in curing patients, more effective than standard artemisinin-based combination therapies, the gold-standard malaria treatment introduced more than 20 years ago, whose use has been undermined since the emergence of partial resistance. The developers say that, pending regulatory approval, the new treatment could be rolled out within the next few years. South African pharmaceutical company Biovac is launching trials of a cholera vaccine, which, if it proves successful, could become the first vaccine developed from start to finish on the African continent. Africa faces the brunt of the global cholera burden but is almost entirely reliant on vaccines made internationally, which has become increasingly challenging in recent years as cases have risen sharply around the world and vaccine stocks have diminished. The African Union has committed to increasing the proportion of routine vaccines used in Africa that are manufactured on the continent from just 1 percent now to 60 percent over the next 15 years, an effort triggered by the access challenges African countries faced during the COVID-19 pandemic. 

The World Health Organization's (WHO's) TB Vaccine Accelerator Council recently published a new report calling for action to ensure equitable access to future tuberculosis (TB) vaccines currently in the pipeline. While the only licensed vaccine for TB is 100 years old and has limited effectiveness in adolescents and adults, as of September, there are 16 candidate vaccines in clinical development, six of which are in Phase 3 trials. WHO estimates that a vaccine for adolescents and adults that is at least 50 percent effective could avert up to 76 million TB cases and 8.5 million deaths over 25 years. However, as the report claims, global demand could far exceed supply in the initial years after a vaccine is approved because there is no designated funding for such a rollout in low- and middle-income countries most affected by TB, which are already facing significant funding shortfalls. In anticipation of these potential bottlenecks and barriers to access, the report identifies six solutions to encourage countries with a high burden of TB, manufacturers, and other funders and stakeholders to start preparing now for the rollout to ensure future vaccines can reach people who need them faster. In a Phase 1 randomized controlled trial, an experimental intranasal vaccine against multiple H5N1 avian flu strains generated a broad immune response, demonstrating the potential of such a vaccine to play a major role in preparing for outbreaks of emerging viruses with evolving strains, as H5N1 continues its worrying spread. The University of Maryland research team tested the vaccine against a placebo in 40 adults between 18 and 45, finding that the vaccine was safe, well-tolerated, and stimulated immunity at various doses. One group received a vaccine dose combined with an adjuvant, an ingredient used to trigger a stronger immune response, and their immune systems were better able to neutralize infected cells for longer, suggesting that the use of an adjuvant could be a promising approach that might allow for lower doses, which could stretch limited vaccine supplies in the event of an outbreak. Last week, IAVI published new findings from the first-in-human Phase 1 clinical trial of its Lassa virus vaccine candidate, which show that one dose of the vaccine triggers robust and long-lasting immunity and is safe. There are no vaccines or treatments currently licensed against the dangerous illness, which causes thousands of deaths in endemic West Africa and has been designated as a priority pathogen with pandemic potential. The trial enrolled 114 volunteers in Liberia and the United States. The candidate, now undergoing a Phase 2a trial in West Africa, is currently the most advanced Lassa fever vaccine candidate in the pipeline and uses the same platform as Merck’s single-dose Ebolavirus vaccine, which is approved in more than a dozen countries.