Breakthroughs Blog: Tuberculosis

The last few years have highlighted more than ever the incredible power of vaccines—from the millions of lives saved by the unprecedented rapid development of COVID-19 vaccines to the approvals and early-stage rollout of the first-ever vaccines for malaria and chikungunya.  We are now fortunate to have vaccines to prevent more than 20 life-threatening diseases, and immunization currently prevents 3.5 to 5 million deaths every year. While it is vital that countries continue to strengthen routine immunization programs to reach the 20 million children who missed out on one or more of their vaccines in 2022, it is also important that countries sustain strong investments in research and development to deliver the next generation of breakthrough vaccines.In recognition of World Immunization Week 2024, GHTC is highlighting five vaccines in development that could be game changers for some of world’s most threatening diseases, reminding us not only of the tremendous impact vaccines have already had but also of the great promise of innovative vaccines to save even more lives in the future.1. TBIn 2022, 1.3 million people worldwide died from tuberculosis (TB), which is the second leading infectious disease killer after COVID-19. Currently, the only approved vaccine for TB is the bacille Calmette-Guérin, or BCG, vaccine, which was developed more than 100 years ago. Though effective at preventing some types of TB in infants, it offers inconsistent protection in adults and adolescents against pulmonary TB, which is why new vaccine options are urgently needed.Last month, the Bill & Melinda Gates Medical Research Institute announced the launch of a pivotal Phase 3 trial evaluating a novel vaccine for TB, which researchers hope could become the second licensed vaccine for TB. The adjuvanted subunit vaccine M72/AS01E vaccine was originally developed by GSK, along with Aeras and IAVI. The trial, which is supported by the Bill & Melinda Gates Foundation and the Wellcome Trust, is testing the vaccine’s ability to prevent latent TB from progressing to active pulmonary TB in adults and adolescents. While it is expected that the trial could take at least five years, if successful, it could lead to an urgently needed new tool with the potential to transform TB control globally.2. ZikaZika is a mosquito-borne virus that can cause congenital malformations in infants born to individuals infected during pregnancy, as well as preterm birth and miscarriage. There are currently no vaccines available to prevent or treat Zika, nor are there specific treatments.There have been numerous outbreaks of Zika around the world, with a widespread outbreak in the Americas just under a decade ago sparking the World Health Organization (WHO) to declare a Public Health Emergency of International Concern in 2016.Last month, Valneva announced the launch of a Phase 1 clinical trial to investigate the safety and immunogenicity of a vaccine against the Zika virus. The second-generation adjuvanted inactivated vaccine candidate, VLA1601, will be tested in 150 adult participants in the United States, with the first topline data from the trial expected as soon as early next year. Additionally, Moderna is advancing an mRNA-based Zika vaccine, mRNA-1893, which is currently in a Phase 2 trial in the United States and Puerto Rico; the trial is expected to end in July 2024.3. Lassa feverLassa fever is an acute viral hemorrhagic illness that is endemic primarily in parts of the West African region. Annually, there are around 5,000 deaths from Lassa fever and an estimated 100,000 to 300,000 cases. There are currently no approved vaccines that protect against Lassa fever.This month, the first participants were vaccinated in a Phase 2 clinical trial of a vaccine candidate for Lassa fever virus, which is being led by an international collaboration between IAVI, the Coalition for Epidemic Preparedness Innovations (CEPI), and in-country partners in Nigeria. The hope is that this trial, which is the most advanced Lassa vaccine trial to date, will lead to the availability of a vaccine candidate for evaluation and use in future Lassa outbreaks and, eventually, an approved vaccine for routine immunization.  4. Nipah virusNipah virus is a zoonotic virus that can cause a wide range of illnesses, from asymptomatic infection to severe respiratory illness and, sometimes, fatal brain inflammation. Nipah has an estimated case fatality rate of 40 to 75 percent, with South Asia facing the greatest burden of outbreaks. There are currently no specific drugs or vaccines for Nipah virus infection.The first human trial of a new vaccine against the deadly Nipah virus began in January of this year after the work, which started in 2017, was paused during the COVID-19 pandemic. The new vaccine, ChAdOx1 NipahB, which was developed using the same viral vector vaccine technology as the University of Oxford and AstraZeneca’s COVID-19 vaccine, will be evaluated over the next 18 months in a Phase 1 trial led by the Oxford Vaccine Group and funded by CEPI.5. ETECEnterotoxigenic Escherichia coli (ETEC) is one of the leading causes of moderate and severe diarrhea in children worldwide. It is estimated that ETEC causes about 220 million diarrhea episodes globally each year, resulting in an estimated 42,000 child deaths. There are currently no approved vaccines for ETEC, and bacterial resistance to the antibiotics often used to treat it is growing globally, underscoring the need for a preventative vaccine.ETVAC is an oral vaccine candidate for ETEC developed by Scandinavian BioPharma, which is being advanced in two different formulations, one for travel use, adults, and older children and a second “self-contained” solution requiring no mixing, which is designed for ease of administration in children under five in low- and middle-income countries. The vaccine has shown promising results in both populations in Phase 1 and 2 trials, which received partial funding from PATH through the Bill & Melinda Gates Foundation, and a Phase 2b trial was implemented among nearly 5,000 children in The Gambia, with efficacy results expected later this year, alongside the potential launch of a planned Phase 3 study in Zambia. If successfully advanced and approved, an ETEC vaccine could be a powerful new tool in our arsenal to reduce suffering and death from diarrheal disease and slow the emergence of antimicrobial resistance.  Breakthrough technologies like these vaccine candidates are possible because of long-term, consistent investment throughout the R&D process, from early-stage product development to implementation and rollout. With these promising technologies and more on the horizon, it is critical that we sustain investment in R&D to push these exciting new tools over the finish line and ensure everyone everywhere can access them. Learn more about global efforts for World Immunization Week to recognize the lifesaving power of vaccines here. 

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. As the dengue outbreak in Latin America has continued to grow and the threat of dengue continues to rise globally due to climate change, better and cheaper vaccines are on the horizon but are unlikely to be available soon enough to address the current crises. Currently approved vaccines for dengue include one expensive two-shot regimen and one that can only be given to people who have already been infected. A new, single-dose vaccine designed to target all four strains of the dengue virus, which was created by the US National Institutes of Health and licensed for development by the Brazilian Instituto Butantan, provided strong protection in a Phase 3 trial. The institute plans to submit the vaccine to Brazil’s regulatory agency for approval within the next few months, and if approved, the institute could start producing tens of million doses next year. Merck also licensed the vaccine technology and is developing a related vaccine for the rest of the world but has yet to test it in a clinical trial. In the meantime, the Brazilian government bought global supply of Takeda’s Qdenga vaccine, which, at a steep per-dose price, will provide some protection during the current outbreak. Takeda’s vaccine has also been licensed to an Indian generic drugmaker, but a slow start-up process means that is unlikely to be available before 2030.Pfizer recently announced that its RSV vaccine demonstrated the potential to protect adults between 18 and 50 at high risk of severe illness in a late-stage clinical trial, offering the promise of a tool to protect a far broader population against the virus that not only causes thousands of hospitalizations and deaths among older Americans and hundreds among infants every year but also can also cause severe illness in younger adults with weakened immune systems or underlying chronic conditions. Abrysvo is currently approved in the United States and elsewhere for adults 60 and older and expectant mothers. Pfizer announced plans to submit the final results from the trial for expanded approval of Abrysvo, although a timeline for submission has not yet been disclosed. Last fall, GSK released late-stage trial data demonstrating that its RSV vaccine could protect adults between 50 and 59 years old, and the US Food and Drug Administration is expected to make its decision on that vaccine in June.A research team from the Centre for Clinical Microbiology at University College London has developed a new method for testing tuberculosis (TB) that would allow lower-resourced laboratories in low- and middle-income countries (LMICs) to process samples safely, with the method primarily aimed at use for monitoring drug treatment response and clinical trials. The World Health Organization recommends monthly treatment monitoring with sputum culture to ensure patients are adhering to treatment to reduce the emergence of multidrug- or rifampicin-resistant TB, but monitoring with culture is often unavailable or incredibly slow in LMICs. The new method cuts out the need for a culture; uses common instrumentation available in most laboratories, even in LMICS; does not have high energy requirements; and takes only three or four hours to return a result. The method is already being used in clinical studies.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. The International Vaccine Institute (IVI) has initiated a technology transfer, first announced last year, of the simplified Oral Cholera Vaccine (OCV-S) to Indian company Biological E. Limited. In the face of an unprecedented rise in cholera outbreaks around the world in recent years, the technology transfer aims to increase the volume of affordable cholera vaccines in the Indian and international markets. IVI is providing technical information, know-how, and materials to support clinical development and regulatory approvals of the vaccine. OCV-s is a simplified formulation of the Oral Cholera Vaccine that can lower production costs while increasing capacity for manufacturers.The Bill & Melinda Gates Medical Research Institute last week announced the launch of a Phase 3 trial evaluating a vaccine for tuberculosis (TB), which researchers hope could become the second licensed vaccine for TB in more than 100 years. The adjuvanted subunit vaccine M72/AS01E was originally developed by GSK, Aeras, and IAVI. The trial, funded by the Bill & Melinda Gates Foundation and the Wellcome Trust, is testing the vaccine’s ability to prevent latent TB from progressing to active pulmonary TB in adults and adolescents. If successful, the pivotal trial could lead to a new tool with the potential to transform TB control globally.A research team from the University of Pittsburgh School of Medicine has identified drug candidates that demonstrate the potential to eliminate the HIV viral reservoir that cannot be expelled completely by existing antiretroviral drugs, preventing people who have undetectable viral load from being completely cured of HIV. The drug candidates, which are called proteolysis targeting chimeras, or PROTACs, can trigger the degradation of the viral protein that prevents the immune system from destroying infected cells by hiding signs of the virus on the surface of the cell. Through this method, the drugs show promise in reversing the ability of HIV to evade detection by the immune system. The PROTAC approach still has significant hurdles to go before it can be used in humans, including preclinical testing in animal models and medical chemistry optimization.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. The Genomic Surveillance Unit at the Wellcome Sanger Institute and the Centre for Epidemic Response and Innovation at Stellenbosch University are partnering to advance the practice of genomic surveillance, which has been around for decades but really came to the forefront during the COVID-19 pandemic and has the potential to improve global efforts against other infectious diseases, including malaria and cholera. During the COVID-19 pandemic, there was huge global investment in genomic surveillance infrastructure, with the Stellenbosch lab being the first to confirm the discovery of the Beta and Omicron variants. In the last year alone, the work of the two labs has contributed to doubling the number of sequences available for dengue, chikungunya, and malaria parasites. Genomic surveillance uses sequencing to get data about the genetic material of a pathogen, which is then used to track how the pathogen is changing or spreading.Researchers from the Health and Medical Research Institute at Japan’s National Institute of Advanced Industrial Science and Technology have developed a bioluminescent assay that could serve as a rapid, low-cost, and convenient test to complement laboratory testing for COVID-19. The test uses a bioluminescent molecule found in some small crustaceans that glows when it reacts with the virus that causes COVID-19 in a saliva sample and can be used with commercially available handheld luminometers at the point-of-care. The research team is planning for initial commercialization in the Japanese and US markets.ProteinLogic and Stellenbosch University will use a $1.35 million grant from the Bill & Melinda Gates Foundation to determine whether an immunoassay technology being developed by ProteinLogic can be used to monitor treatment response to tuberculosis (TB) antimicrobial chemotherapy in patients. ProteinLogic's ImmiPrint testing technology is a protein-based test based on predictive models developed through machine learning that aims to offer rapid, efficient, and cost-effective discovery of diagnostic biomarkers across multiple diseases. Its new partner, Stellenbosch University, has been leading clinical trials on TB diagnostic biomarkers. In the face of the growing threat of drug-resistant strains of Mycobacterium tuberculosis, there is an urgent need for new technologies to monitor the effectiveness of current treatments, in addition to the need for novel treatments and prevention methods for TB.