 Dr. Hui Ma
Research Fellow in Trinity Biomedical Sciences Institute
Trinity College Dublin
Ireland |
Title:
dmLT Enhances Mucosal Immunity and Enables Dose-Sparing in Oral Cholera Vaccination
Abstract:
Cholera remains a significant global health threat, with a sharp increase in cases reported by the World Health Organization in 2024–2025, coinciding with a critical shortage of oral cholera vaccines. Vaccines such as Dukoral® are effective but limited by supply and weak mucosal responses in low-dose or vulnerable populations.
Oral vaccines offer distinct advantages over injectable formulations, including the potential to reduce infection and transmission, simplified logistics, lower costs, and improved patient compliance. Yet, despite these benefits, only eight oral vaccines are currently licensed for clinical use. A key limitation is their relatively low immunogenicity compared to injectable vaccines. While adjuvants are commonly used to enhance the efficacy of injectable vaccines, none are currently approved in licensed oral vaccines.
This study aims to address this gap by identifying safe, effective, and affordable adjuvant–antigen combinations that retain immunostimulatory activity within the gastrointestinal tract. We evaluated dmLT, a recombinant double-mutant derivative of Escherichia coli heat-labile toxin with reduced toxicity and well-characterized mucosal adjuvanticity, as an oral adjuvant to enhance the immunogenicity and efficacy of cholera vaccination.
In a murine model, oral co-administration of Dukoral® with a low dose of dmLT (1 µg/mouse) led to a 16-fold increase in functional fecal IgA capable of neutralizing cholera toxin, compared to vaccine alone. dmLT also significantly elevated systemic IgG, IgA, and IgG2c titers, and enhanced Th1/Th17-associated cytokine responses (IFN-γ and IL-17) in splenocytes and mesenteric lymph nodes. Intestinal IgA levels were markedly increased across all gut compartments, and rCTB-specific IgA responses were also significantly enhanced, suggesting broader utility of dmLT in protein-based oral vaccines.
These findings underscore the potential of dmLT to not only strengthen mucosal immunity but also enable dose-sparing strategies, which are essential for maximizing vaccine coverage amid global shortages. dmLT represents a promising platform for next-generation oral vaccines targeting cholera and other enteric pathogens, particularly in outbreak-prone or resource-limited settings.
Biography:
Dr. Hui Ma (Fay) is a senior Research Fellow at Trinity College Dublin, with over 16 years of experience in biopharmaceutical research and development. Her expertise lies in antibody engineering, oral vaccine adjuvant development, and immunoassay innovation. She holds a Ph.D. in Applied Biochemistry from Dublin City University, where she focused on targeted neurotherapeutics for chronic inflammatory pain. Dr. Ma has led and contributed to over 20 national and international research collaborations, bridging academia and industry to develop novel diagnostics and therapeutics. She has authored 26 peer-reviewed publications (15 as first author), generated seven invention disclosures, filed two patents, and licensed antibody technology to industry. She serves as a topic editor for Frontiers in Immunology and Frontiers in Sensors, and actively reviews for leading scientific journals. Her ongoing research focuses on enhancing mucosal immunity and dose-sparing strategies in oral vaccination for Melioidosis and enteric pathogens using novel oral adjuvants.
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