Breakthroughs Blog: Pandemic preparedness

Last week, Cepheid announced that its Xpert Hemorrhagic Fever Panel test has received Emergency Use Listing from the World Health Organization, enabling the technology to be deployed to help identify suspected cases and support outbreak containment in the rapidly growing outbreak of Bundibugyo Ebola in the Democratic Republic of the Congo. The molecular panel test detects and identifies Ebola virus (multiple strains, including Bundibugyo), Crimean-Congo hemorrhagic fever, Marburg virus, and Lassa virus, providing results in around an hour. The test runs on Cepheid’s GeneXpert diagnostic technology system, which is already widely used across Africa, helping enable rapid implementation. Cepheid previously donated an initial shipment of tests cleared by the US Food and Drug Administration through the Department of War, and the new listing now enables further deployment. A Phase 2 clinical trial led by the Serum Institute of India found that an experimental monoclonal antibody for dengue virus was safe, well-tolerated, and provided evidence of efficacy in a Phase 2 clinical trial. Dengue affects more than 200 million people each year and is a growing global threat due to the expanding range of the virus-carrying mosquito species. There are several licensed vaccines for dengue but no licensed antiviral drugs. The experimental antibody previously neutralized all four serotypes of dengue virus in animal studies and demonstrated safety in a Phase 1 trial in healthy adults. Researchers at the National Institutes of Health (NIH) have discovered rare antibodies that could inform the development of a therapeutic or preventive intervention for alpha-gal syndrome, an emerging tick-bite-associated condition behind a growing number of cases in the United States and globally, which can lead to allergic reactions to a molecule in red meat and other animal products. The discovery was made through malaria research—the scientists were originally trying to find antibodies that could target alpha-gal (a sugar molecule) on malaria parasites as a potential strategy for malaria prevention. In laboratory tests, the rare antibodies successfully hindered human allergic antibodies from binding to red meat allergens. There are currently no specific treatments or preventions for alpha-gal syndrome.

The Gates Foundation has awarded ProFound Therapeutics up to $35 million to find new drug targets for preeclampsia, a high blood pressure condition during pregnancy that can be severe for mother and child and is a significant contributor to maternal and fetal deaths globally, particularly in low- and middle-income countries. ProFound will utilize their vast repository of proteins and data to improve scientific understanding of how preeclampsia is developed in the body, with the goal of identifying promising approaches for future drug development. Once targets are identified, the company will explore their features using an AI tool and then evaluate them in laboratory experiments.Last week, the Coalition for Epidemic Preparedness Innovations (CEPI) announced that it will invest up to $16.5 million to advance the development of an African-developed vaccine candidate for the Bundibugyo strain of Ebola, which is behind the fast-growing outbreak in the Democratic Republic of the Congo. CEPI’s support will help advance the candidate through preclinical development and into an early-stage clinical trial in Africa. The vaccine candidate uses a technology that is utilized by a licensed vaccine against smallpox and mpox and has elicited long-term immunity in a vaccine targeting the Zaire strain of Ebola. It is the fifth Bundibugyo-specific vaccine candidate supported by CEPI in response to the current outbreak and the only of the five designed to induce two major parts of the immune system, both B- and T-cells, for comprehensive and long-lasting immunity.A novel tuberculosis (TB) vaccine candidate failed to match the current, more-than-100-years-old vaccine in preventing TB infections in newborns, according to the recently shared results of a Phase 3 trial conducted among 6,897 healthy newborns in sub-Saharan Africa. TB remains the world’s leading infectious disease killer and there is an urgent need for a new vaccine—the current TB vaccine, BCG, is effective at preventing some types of TB in infants, but it offers inconsistent protection in adults against pulmonary TB. One of 17TB vaccine candidates in the pipeline, the vaccine in the trial, VPM1002, is a genetically modified recombinant BCG vaccine developed by the Serum Institute of India. While disappointing, the results of the trial do provide significant insights about how best to design robust, feasible efficacy trials for future vaccine candidates.

Last Thursday, the World Health Organization (WHO) announced that, with support from Gavi, the Vaccine Alliance, it will allocate 70,000 doses of an approved Ebola vaccine to the Democratic Republic of the Congo, which is facing the largest Ebola outbreak in the country’s history. The vaccine, Ervebo, targets Ebola Zaire, the most common Ebola strain, not the Bundibugyo strain behind the current outbreak—for which there are no approved vaccines —but early laboratory and animal data suggest it may provide some cross-protection. Twenty thousand doses will be used in a Phase 3 trial to evaluate whether the vaccine offers cross-protection for Bundibugyo, while the remaining doses will be allocated to frontline health care workers, serving the dual goals of providing some protection for at-risk populations against severe illness and death during the current outbreak while gathering critical data to inform use of the vaccine in future Bundibugyo outbreaks.Researchers at the Walter and Eliza Hall Institute of Medical Research have developed a rapid blood test that could improve detection of iron deficiency, a widespread health challenge disproportionately affecting mothers and children in low-resource settings where access to conventional laboratory-based screening methods are limited. Using a finger-prick blood sample, the test provides results within 15 minutes without the need for specialized laboratory infrastructure and highly trained health care providers. It has demonstrated strong correlation with gold-standard laboratory methods used in high-income countries and includes a built-in reference line to make the results easier to interpret. The test is currently undergoing evaluation in sub-Saharan Africa.The Coalition for Epidemic Preparedness Innovations (CEPI) shared last week that it will dedicate $4.17 million to four research projects designed to assess whether additional vaccines currently or previously licensed against Ebola Zaire could offer some cross-protection against severe illness and death during the current rapidly growing outbreak of Bundibugyo Ebola. Specifically, the funding will go to teams at the University of California, Los Angeles in the United States; the Institute of Tropical Medicine in Belgium; the University of Oxford in the United Kingdom; and the MRC-University of Glasgow Centre for Virus Research in the United Kingdom. The research teams will use blood samples from vaccinated individuals to assess immune responses and potential cross-reactivity of antibody responses, helping establish and standardize antibody tests for Bundibugyo, inform interpretation of clinical trial results, and guide future strategies. These research initiatives will support trials during the current outbreak and complement ongoing efforts to develop Bundibugyo-specific vaccines. 

Last week, the US Food and Drug Administration (FDA) approved Moderna’s flu vaccine for older adults, making it the first licensed mRNA flu shot. The approval follows objections raised by FDA earlier this year that put the future of the application in question. Compared to traditional influenza vaccines, mRNA vaccines can be produced much more quickly, allowing public health experts to wait longer before selecting strains to target for the upcoming flu season, increasing the likelihood that the vaccine will match the strains actually circulating. Beyond regular flu season, faster vaccine production and the approval of this seasonal shot could help speed up the development and approval of a pandemic flu vaccine. FDA specifically issued a standard approval for the vaccine for adults between 50 and 64 and an accelerated approval for adults 65 and older—Moderna has agreed to do a post-licensure trial to gather more data on effectiveness in this group. The company expects some doses will be available ahead of the upcoming flu season. The results of a Phase 3 clinical trial published in the New England Journal of Medicine last week showed that a once-weekly oral HIV treatment maintained viral suppression as effectively as a standard daily treatment regimen, pointing to a potential new treatment alternative for people living with HIV. This option could increase convenience for patients taking daily pills and doesn’t require the regular clinical visits associated with long-acting injectable options, especially for patients who experience stigma or have other health conditions requiring treatments to manage. The study regimen consisted of a once-weekly combination tablet containing islatravir and lenacapavir, which was evaluated in adults whose HIV had remained suppressed for at least six months through a daily regimen across 12 countries. The first participant has been dosed in a first-in-human trial of Moderna’s vaccine candidate against Bundibugyo, the strain of Ebola behind the deadly ongoing outbreak in the Democratic Republic of the Congo, which has now become the second-largest Ebola outbreak in history. There are currently no vaccines or treatments available for Bundibugyo Ebola. The vaccine candidate, mRNA 1469, uses Moderna’s mRNA platform, which is also used in the company’s COVID-19 vaccine. The Coalition for Epidemic Preparedness Innovations (CEPI)-supported trial is being conducted at three Canadian sites among healthy adult volunteers to assess the safety and tolerability of the candidate and evaluate immune response. If the vaccine candidate successfully advances to approval, Moderna has committed to working with CEPI to urgently make doses available to low- and middle-income countries at accessible prices.