Breakthroughs Blog: Antimicrobial resistance

A new study sheds light on the findings of a recent trial evaluating the ability of a laboratory-made broadly neutralizing antibody (bnAb) to prevent HIV infection, pointing to approaches that could lead to more successful future antibodies and vaccines. bnAbs are naturally occurring antibodies that can neutralize multiple strains of HIV; they are considered a promising approach in HIV prevention research. A large, multicountry clinical trial evaluating a laboratory-made bnAb found that it did not significantly reduce overall HIV infections, although it showed some ability to reduce infections caused by highly sensitive strains. In the new study, researchers examined what happened in the participants who received the bnAb, discovering that there were extended periods of time when their antibody levels were too low to block less-sensitive strains of the virus. The study results suggest that more potent antibody concentrations and combinations of antibodies that attack the virus in different ways could have more success.An international research team has identified a crucial compound in the saliva of virus-carrying mosquitoes that could lead to a new prevention strategy for multiple mosquito-borne viruses. The researchers found that when mosquitoes infected with two orthoflaviviruses, West Nile virus and Zika virus, bite, their saliva contains not only the virus but also a viral compound that promotes infection by inhibiting the body’s initial immune response that is triggered when a virus enters the skin. The findings suggest that this viral compound could be shared among other orthoflaviviruses as well and could be a promising target for a preventive vaccine against multiple viruses from this group. The researchers have developed a vaccine targeting the compound that is now being optimized for clinical evaluation. New research from scientists in the United Kingdom highlights a new mechanism that a dangerous fungus uses to evade antifungal treatments. Candida auris is a priority pathogen that has caused outbreaks globally over the past two decades and can be highly fatal for vulnerable hospitalized patients. Current antifungal drugs work by targeting fungal cell walls, hindering the fungi from expanding. The researchers found that one way C. auris eluded treatment was by creating multiple versions of its entire genome, including a wide range of mutations in a specific gene that plays a key role in cell wall integrity. These findings point to new pathways for developing next-generation antifungals and combination antifungal regimens.

A study from the University of California, San Francisco found that a new long-acting HIV combination treatment could provide an alternative, more accessible option for some people with HIV. Long-acting treatment options can provide a simpler, more convenient alternative to daily pills for people living with HIV, but the only approved long-acting combination includes rilpivirine, which is not available in low- and middle-income countries, and the virus has been known to develop resistance to it and similar drugs. The new combination under study replaces rilpivirine with lenacapavir, which uses a different mechanism to target the virus. In the study, all participants achieved and maintained control of the virus. Additional clinical trials are planned to evaluate the approach more comprehensively, but, in the meantime, these findings could help guide care.  A team of researchers at the Massachusetts Institute of Technology has found a way to keep mRNA vaccines stable at higher temperatures, which could drastically lower costs and improve access to the technology in low-resource settings around the world. mRNA vaccines must be kept at extremely cold temperatures during transport and storage, requiring high costs and continuous monitoring. The researchers adjusted the formulation of the tiny particles that carry the mRNA, making them more resistant to heat. The vaccines the team produced can be stored at room temperature for up to a year or at nearly 100 degrees Fahrenheit for two months. Even after storage, the shots elicited equivalent immune responses in mice to the original formulations.The Medical Research Council/Uganda Virus Research Institute and the London School of Hygiene and Tropical Medicine have launched a Phase 1 clinical trial in Uganda evaluating the safety and immune response of a vaccine candidate for Bundibugyo, the severe strain of Ebolavirus behind the ongoing outbreak in the Democratic Republic of the Congo for which there are currently no licensed vaccines. Conducted in partnership with the Oxford Vaccine Group and Pandemic Science Institute at the University of Oxford, the trial builds on an ongoing Phase 1 trial of the same candidate in the United Kingdom. Both trials are funded by the Coalition for Epidemic Preparedness Innovations (CEPI). The candidate, ChAdOx BDBV, was developed by scientists at the University of Oxford and uses the same platform as the Oxford/AstraZeneca COVID-19 vaccine. 

Recently published results from a large multi-country study found that pooled tuberculosis (TB) testing could greatly reduce costs and boost access to diagnosis. Access to the gold standard of rapid molecular testing is limited—only just over half of people diagnosed with TB in 2024 were first tested using the technology. Instead, they were diagnosed using older technology, which can take weeks to produce results, during which the infection could progress or be transmitted to others. Millions of additional individuals with TB go completely undiagnosed. A major contributing challenge is that rapid molecular testing requires an expensive diagnostic cartridge for each sample. Pooled testing involves testing samples from multiple individuals with one cartridge. Patients are only retested individually if the result is positive. Unlike new diagnostic technologies, like AI-enabled portable X-ray machines, that are promising but would require additional funding to implement, pooled testing could be scaled up rapidly without new funding because it utilizes technologies that many labs already have.Medicines for Malaria Venture (MMV) is advancing the novel, first-in-class antimalarial compound, cabamiquine, into the next stage of clinical development, with the hope that the compound could be part of a single-dose, long-acting treatment for the prevention and treatment of malaria, which could greatly simplify care compared to current options. Cabamiquine was discovered by researchers at the University of Dundee, with financial and scientific support from MMV, and then advanced by Merck to proof of concept. Recently published results from two Phase 2a trials showed that a regimen of cabamiquine and pyronaridine was able to clear uncomplicated Plasmodium falciparum malaria in more than 90 percent of participants and demonstrated a strong safety profile. MMV will now lead Phase 2b clinical development of the compound. The Biomedical Advanced Research and Development Partnership (BARDA) recently announced that it has awarded Scynexis a $214 million contract for the development of an antifungal to treat and prevent invasive fungal infections, the less common but more serious form of fungal infection that penetrates deep into the tissues of the body. Fungal infections are a growing global challenge, but there is a significant gap in the pipeline of new tools to address them. Last year, the company reported positive findings from a Phase 1 trial of an oral dose of the candidate and is currently conducting a Phase 1 trial of an intravenous formulation. The award includes initial funding to advance the company’s antifungal candidate into Phase 2 trial, with an option for additional, longer-term funding. 

Fungi have existed for hundreds of millions of years, long before dinosaurs walked the Earth, but fungal infections have become a rapidly growing challenge for human health in recent decades.Fungal diseases affect more than 300 million people each year, disproportionately impacting people in low-resource settings and those with weakened immune systems, including people living with HIV, cancer patients, and transplant recipients. Most fungal infections affect superficial tissue like the skin, nails, or hair and can cause chronic illness and productivity loss. Though less common, invasive fungal infections can spread throughout the body and are associated with high mortality.Why fungal diseases are becoming harder to ignoreThe rising incidence of fungal infections is driven by a variety of factors, including conflict, poverty, urbanization, pollution, travel, and climate change, which increase exposure, heighten vulnerability, and expand the reach of dangerous fungal pathogens. At the same time, advances in medicine mean more people are living longer with conditions that weaken the immune system, increasing the number of people at greater risk. Growing antifungal resistance is also making infections harder to treat and further limiting already scarce treatment options.Despite the mounting burden, fungal disease remains underprioritized, underdiagnosed, under-surveilled, and underfunded, making it one of the world’s most neglected global health threats.Why innovation is falling behindFungal infections receive less than 1.5 percent of all infectious disease research and development (R&D) funding, contributing to sparse pipelines for both therapeutics and diagnostics. Closing these gaps will require greater investment in R&D, particularly for tools designed for resource-constrained settings and targeting the pathogens that pose the greatest threat to human health. Stronger regulatory and procurement systems and international collaboration will also be essential to ensure emerging tools are affordable and accessible worldwide.Despite persistent gaps, several promising innovations demonstrate the potential for R&D to transform the global response to fungal disease.Promising advances in antifungal treatmentThere are currently only four classes of antifungal medicine available, many of which are associated with serious side effects or require lengthy, hospital-administered treatment courses. The pipeline of new antifungal therapies also remains thin.The World Health Organization (WHO) reported last year that only nine antifungal therapies were in clinical development to address WHO’s designated top four priority pathogens, including three in Phase 3 development. Although the Phase 3 trial for one of those candidates has since been terminated, another candidate, olorofim, developed by Shionogi and F2G, recently reported positive Phase 3 trial results. If approved, it could become the first antifungal treatment with a novel mechanism of action for that infection in more than 20 years.Earlier-stage research is also yielding promising advances. Researchers recently discovered that an antibiotic could target a priority fungal pathogen by switching it back from its invasive form to a less harmful form. This antibiotic could help existing antifungal drugs target dangerous fungal pathogens, allowing lower, less toxic doses of those drugs to be used.Together, these advances offer hope of a new generation of antifungal therapies.The future of fungal diagnosticsDiagnostic tools for critical fungal pathogens exist but with significant limitations, including invasive sampling requirements, long turnaround times, limited pathogen coverage, and inadequate sensitivity. Many also depend on sophisticated laboratories and highly trained staff, making them difficult to deploy in resource-constrained settings globally that bear a disproportionate burden of fungal disease.The MycoMEIA® assay developed at Johns Hopkins University and commercialized by Pearl Diagnostics represents a recent advance in antifungal diagnostics. The test received US Food and Drug Administration clearance in 2025. It uses a urine sample, which is much simpler and less invasive for patients than current options, and provides results in just a few hours.Another promising research development illustrates where fungal diagnostics may be headed next. Researchers at the Mayo Clinic and Zepto Life Technology recently reported early results from a new diagnostic platform that was able to identify 18 different fungal pathogens with a single test. While still in development, such approaches could not only streamline diagnosis for health care providers and patients, but also reduce costs and resource requirements, making them well-suited for resource-constrained settings.Closing the innovation gap Fungal diseases and antifungal resistance are attracting greater international attention, but the response still lags behind the scale and pace of this growing threat. Increased investment in the R&D of fit-for-purpose innovations, paired with stronger regulatory and health systems and global coordination, will be crucial to ensure new diagnostics and treatments emerge from the pipeline and reach the patients who need them most.