Assoc. Prof.
Nguyen Duc Hoang
Center for Bioscience and Biotechnology, VNUHCM-University of Science, Vietnam
Title: Antigen Display at Different Cellular Locations in Bacillus subtilis for Mucosal Vaccine Delivery and Induction of Immune Responses
Nguyen Duc Hoang
Center for Bioscience and Biotechnology, VNUHCM-University of Science, Vietnam
Bacillus subtilis, a model Gram-positive bacterium with generally recognized as safe (GRAS) status, is endotoxin-free and widely used as a probiotic in humans and animals. These features make it an attractive host for antigen production and delivery in mucosal vaccine development. B. subtilis can produce antigens at different cellular locations, including the cytoplasm, extracellular medium, vegetative-cell surface, and spore surface. This presentation summarizes our studies on vegetative-cell and spore-surface display systems for vaccine applications. Initial work demonstrated the covalent attachment of heterologous proteins to the cell wall using Listeria monocytogenes sortase A and the LPXTG sorting motif, achieving approximately 10⁵ α-amylase molecules per cell. Subsequent studies identified the native B. subtilis sortase YhcS and its substrate YhcR, enabling surface display without introducing a heterologous sortase gene. Several displayed antigens enhanced mucosal and systemic immune responses in animal models. The Escherichia coli heat-labile enterotoxin B subunit, displayed using the staphylococcal FnbpB anchoring domain, and a detoxified Staphylococcus aureus alpha-toxin variant, HlaH35LH48L, displayed using YhcR, induced intestinal IgA and systemic IgG responses in mice. In poultry, a chimeric Clostridium perfringens antigen containing CPA, NetB, and ZMP components conferred partial protection against necrotic enteritis through humoral and cellular immune responses. In addition, S. aureus antigens displayed on the B. subtilis spore surface induced antigen-specific immune responses and partial protection in selected murine models. These findings highlight the versatility of B. subtilis as a platform for next-generation oral and mucosal vaccines for human and veterinary applications.
Biography
Dr. Nguyen Duc Hoang obtained his Ph.D at the Department of Genetics, University of Bayreuth, Germany (9/2003-7/2006) for the work on B. subtilis “Construction of plasmid-based expression and secretion vectors and study of the immobilization of proteins on the surface of B. subtilis cells”. Consequently, the first commercial expression plasmids, pHT series, for B. subtilis, was generated, and the expression vectors using controllable stabilizing elements combined with promoters to enhance protein expression level have been developed. In 2006, he moved to the Max Planck Institute for Molecular Physiology. He has been working for the University of Science-VNUHCM since 6/2011, and is currently the director of the Center for Bioscience and Biotechnology. He was Head of the Department of Microbiology from 2012 – to 2021 and was appointed as an associate professor in 2015. He has started working on the Bacillus subtilis expression system since 2003, and his research group currently focuses on gene expression in B. subtilis in different locations, in the cytoplasm, on the surface of vegetative cells and spores, and as secretion into the culture medium. His research group also focuses on vaccine development for cattle and fish using B. subtilis as a vaccine delivery vector.
ORCID: https://orcid.org/0000-0003-2437-3568
Researchgate: https://www.researchgate.net/profile/Hoang-Nguyen-177/research