Breakthroughs Blog: Vaccines

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 Phase 2b trial testing a new regimen for people with chronic Trypanosoma cruzi infection could offer a safer, more practical treatment option for the infection, which affects more than seven million people globally, mainly in Latin America, and can develop into Chagas disease. Compared to the current standard regimen that involves twice-a-day treatment for 60 days and is frequently accompanied by uncomfortable side effects, leading to treatment failure, the new regimen involves a 30-day course taken once daily. Trial participants treated with the shorter regimen had significantly reduced side effects, found it easier to follow, and saw lower treatment interruption. If it continues to demonstrate success in large Phase 3 trials, the regimen could transform treatment for patients globally, as T. cruzi infection becomes a growing challenge in the United States, Europe, and Japan.The first participants have been vaccinated in a trial in the Democratic Republic of the Congo (DRC), where the country’s ongoing outbreak of the Bundibugyo strain of Ebola has now become the largest Ebola outbreak in the country’s history and the second largest in history. Health workers in Bunia, a DRC city at the center of the outbreak, were the first to be vaccinated in the real-world efficacy trial evaluating whether the Ervebo vaccine, which is designed to target the more common Zaire strain, offers some cross-protection against Bundibugyo. There are no approved vaccines for Bundibugyo Ebola, and there were no candidates in late-stage development before the start of the outbreak of the rarer strain of the virus, which has only caused three outbreaks since it was first discovered around 20 years ago. Since the outbreak began, global partners have fast-tracked the development of earlier-stage candidates, but researchers hope the Ervebo vaccine could provide some protection before those candidates are ready for evaluation in DRC. As artificial intelligence (AI) continues to rapidly transform many aspects of technology and science, including health research, a new report from the World Health Organization (WHO) speaks to how stakeholders can help ensure AI-enabled health research is conducted responsibly and benefits everyone. According to the report, while AI has the potential to accelerate health innovation and improve health outcomes, it also presents risks related to equity, privacy, safety, transparency, and more. WHO suggests that researchers, ethics committees, regulators, funders, and policymakers can act to strengthen ethical oversight of AI throughout the health research continuum. WHO also notes that most AI development remains concentrated in high-income settings and contends that strengthening leadership, capacity, and participation in AI in low- and middle-income countries will be important to ensuring the technology does not exacerbate existing inequities in health and health research. 

Last week, the World Health Organization (WHO) prequalified multi-dose vials of the maternal vaccine against respiratory syncytial virus (RSV), enabling rollout in lower-income countries. RSV poses a severe global threat, especially for children under five and newborns, in particular. The Gates Foundation supported the development of a multi-dose version of Pfizer’s Abrysvo maternal RSV vaccine, which is administered to pregnant people in their third trimester, protecting newborns against infection and greatly reducing babies’ risk of being hospitalized with RSV. Multi-dose vials simplify the logistics of vaccination, allowing health care professionals to vaccinate more people with fewer vials, which need to be stored and transported in ultra-cold conditions. The prequalification now enables international organizations, like Gavi, the Vaccine Alliance, which has already put implementation plans in place, to procure them for rollout in low-income countries. A research team has developed a nanobody-based antivenom that could provide a more flexible and effective approach for treating snakebites, which kill tens of thousands of people globally and disable hundreds of thousands more. Traditional venom is made by processing antibody-filled blood from horses injected with small doses of venom, but the quality of these antivenoms can vary, they can cause severe allergic reactions, they are expensive to produce, and they offer inconsistent protection across snakebites from different species. Nanobodies, tiny versions of antibodies, can move through tissue more quickly and reach venom before it can cause permanent damage. In a new study, all mice treated with the nanobody-based treatment survived. The treatment also prevented the most severe effects of the venom, is not expected to cause unwanted side effects, and remained intact at high temperatures, which is key in the resource-constrained rural settings that face heightened risk. Further studies will be needed to optimize the dose and ensure safety and efficacy in humans, but the study suggests that nanobody-based antivenoms could be a promising approach for further study. Immunoscript Life Science will receive up to $8.9 million from the Coalition for Epidemic Preparedness Innovations (CEPI) to further development of its thermostable next-generation self-amplifying RNA (saRNA) vaccine platform, which could help improve access to RNA vaccines globally. mRNA vaccines have demonstrated significant promise as a tool against emerging disease threats because of the speed, flexibility, and adaptability with which they can be produced, but their requirement for ultra-cold temperatures for storage and transportation has proven a barrier to access in low-resource and remote settings. The saRNA vaccine platform, now owned by Immunoscript, is an alternative technology that could help overcome challenges associated with the cold chain. With CEPI’s funding, the company will conduct an early-stage trial in people in India to assess the safety and immune response of the technology. 

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.