A groundbreaking international collaboration between the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and LifeArc has been launched, aiming to address a severe unmet need in global infectious disease therapeutics. This partnership is focused on developing an affordable and accessible monoclonal antibody (mAb) treatment targeting Crimean-Congo Hemorrhagic Fever Virus (CCHFV), a tick-borne pathogen responsible for thousands of infections annually with a high fatality rate. By leveraging decades of virological expertise and advanced antibody engineering technology, this endeavor seeks to create an innovative pharmaceutical solution capable of both treating and preventing this devastating viral infection, especially in low- and middle-income countries (LMICs) where health resources are limited.
The team’s initial discovery, dating back to a pioneering 2019 study published in Science Advances, revealed a monoclonal antibody effective against the CCHFV strain 10200 in murine models. The antibody itself binds to a viral glycoprotein known as GP38, a critical target uncommon among traditional neutralizing antibodies. Intriguingly, this suggests that CCHFV protection mechanisms may diverge from classical paradigms, as neutralizing antibodies historically considered essential against viral pathogens do not significantly influence disease outcomes with this virus. This nuanced understanding opens a new frontier in antibody therapeutics, emphasizing the importance of non-neutralizing antibody functions in viral protection.
CCHFV remains endemic across vast geographical regions, including Africa, the Balkans, the Middle East, and parts of Asia, with seasonal outbreaks posing significant risks to both civilian populations and healthcare workers. Estimates from the U.S. Centers for Disease Control and Prevention place annual cases at 10,000 to 15,000 globally, with mortality rates approaching 40 percent. Moreover, the virus’s vector, Hyalomma ticks, are expanding their distribution, raising alarms about possible incursions into Western Europe. This volatile epidemiological landscape creates an urgent need for effective medical countermeasures, particularly considering that no approved therapeutics or vaccines currently exist.
Monoclonal antibodies have revolutionized modern medicine, notably in oncology and autoimmune diseases, yet their application in infectious diseases remains severely limited due to prohibitive costs and manufacturing challenges. Approximately 80% of mAb sales occur in high-income regions such as North America and Europe, resulting in vast disparities in treatment availability. The USAMRIID-LifeArc collaboration aims to circumvent these barriers by prioritizing global accessibility, focusing on developing therapies tailored to the constraints and needs of LMICs. This initiative represents a strategic pivot towards equitable biopharmaceutical development, emphasizing both innovation and affordability.
LifeArc’s robust experience in antibody humanization and development is at the core of this project. The organization has previously contributed to the creation of transformative therapeutics such as pembrolizumab, a breakthrough cancer immunotherapy, and lecanemab, an Alzheimer’s treatment currently advancing global standards of care. Applying this expertise, LifeArc scientists will engineer hundreds of humanized variants of the USAMRIID-discovered monoclonal antibody, screening for efficacy across multiple CCHFV strains. This comprehensive approach ensures the identification of candidates with the broadest possible protective effect, optimizing therapeutic potential before progressing towards clinical development.
Complementing LifeArc’s efforts, USAMRIID will utilize its unparalleled biosafety level 4 (BSL4) containment facilities to conduct rigorous preclinical efficacy testing. CCHFV is classified as a BSL4 pathogen, indicating it requires the most stringent biosafety precautions due to its high lethality and absence of approved treatments. USAMRIID’s expertise and infrastructure enable safe, high-fidelity animal infection models to evaluate the protective capacity of candidate antibodies, ensuring translational relevance. Additionally, the development of vital biological markers by USAMRIID will support subsequent clinical trials by providing essential endpoints for assessing therapeutic response.
The partnership’s financial underpinning is robust: with investments exceeding $2 million from LifeArc, a comprehensive Chemistry, Manufacturing, and Controls (CMC) program is underway to produce clinical-grade monoclonal antibody material. Beyond manufacturing, the collaboration includes strategizing the clinical development pathway, engaging early with global regulatory bodies such as the World Health Organization and endemic country health authorities. This proactive dialogue is aimed at establishing a Target Product Profile that balances efficacy, safety, ease of administration, and cost-effectiveness, thereby maximizing real-world impact in resource-limited settings.
The project also holds profound biodefense implications. CCHFV is designated not only as a highly hazardous BSL4 agent but also as a Category A bioterrorism threat by U.S. authorities. Its potential use as a biological warfare agent, compounded by the lack of countermeasures, raises security concerns. The development of an accessible monoclonal antibody therapy would bolster protections for military personnel deployed in endemic regions and healthcare workers exposed during outbreaks, mitigating risks associated with this viral threat.
Despite the challenging biological and logistical landscape, optimism runs high among the researchers. Dr. Joseph Golden emphasizes the dual utility of the monoclonal antibody product, which could serve therapeutically to ameliorate infection severity and prophylactically to shield healthcare providers and at-risk populations. Dr. Aura Garrison highlights the novel role of GP38-targeting antibodies, noting that protection against CCHFV may rely more on their ability to elicit immune functions beyond neutralization, marking a paradigm shift in antiviral antibody development.
USAMRIID’s extensive portfolio in viral research forms a solid foundation for this endeavor. The institute has dedicated over five decades to deciphering viral pathogenesis, host response mechanisms, and the molecular underpinnings of infection, fostering breakthroughs in vaccines and antiviral therapies. Its Virology Division encompasses multidisciplinary expertise spanning molecular virology, immunology, and cell biology, supported by robust animal models and natural history studies that fulfill critical FDA licensure requisites. This intricate intersection of science and technology positions the collaboration at the cutting edge of viral countermeasure development.
On the philanthropic side, LifeArc’s mission aligns with advancing global health equity by transforming emergent scientific discoveries into widely available medical solutions. Recognizing monoclonal antibodies as a powerful but underutilized tool in infectious disease control, LifeArc’s investment transcends conventional profit-driven models, aiming to dismantle barriers of complexity, cost, and risk that impede treatment dissemination. The organization’s non-profit status underlines its commitment to ensuring that life-saving innovations reach populations most burdened by diseases like CCHFV.
The implications of this project extend beyond the immediate threat of Crimean-Congo Hemorrhagic Fever. By demonstrating that high-containment virus research can be coupled with antibody engineering and global health-driven product development, the partnership sets a precedent for addressing other emerging and neglected viral pathogens. The successful creation and deployment of an affordable monoclonal antibody for CCHFV could catalyze similar efforts worldwide, fostering a future where equitable access to cutting-edge therapies is the norm rather than the exception.
As the collaboration moves toward Investigative New Drug submission and Phase I clinical trials, the scientific community and global health stakeholders will watch closely. The fusion of fundamental virology with translational antibody technology, supported by strategic manufacturing and regulatory planning, embodies a holistic approach to tackling neglected infectious diseases. Ultimately, this project not only aspires to save thousands of lives threatened by a deadly virus but also to redefine how innovation and accessibility converge in the realm of global health.
Subject of Research: Animals
Article Title: (Not provided in the source content)
Web References:
- USAMRIID website: https://usamriid.health.mil/
- DOI link to original study: http://dx.doi.org/10.1126/sciadv.aaw9535
References:
- Original antibody discovery published in Science Advances, DOI: 10.1126/sciadv.aaw9535
Image Credits:
Dr. Janice Williams
Keywords
Monoclonal antibodies, Bleeding, Fever, Mouse models, Clinical trials, Neutralizing antibodies, Pathogenesis, Biosafety, Chemistry, Manufacturing
