Antigen discovery and pathogenesis
The laboratory studies the expression (both at transcriptomic and protein level) of antigens during different stages of colonization and infection, with the goal of identifying proteins that may represent important vaccine targets. A combination of proteomic library creation, in vitro phagocytic killing assays, and in vivo animal models is used to screen protective antigens against invasive infection by different bacterial pathogens. The role of these proteins in the pathogenesis of these bacteria is also actively investigated.
Vaccine development
Drs Lu, Malley, and Zhang have pioneered the development of a groundbreaking technology known as the Multiple Antigen Presenting System (MAPS). This innovation serves as an efficient platform to elicit comprehensive B- and T-cell immunity against polysaccharide (PS) and protein antigens. The versatility of MAPS holds promise for developing novel vaccines against various human pathogens, where both humoral and cellular immunity are crucial for protection. Animal studies have demonstrated potent immune responses specific to the target pathogens, with ongoing preclinical investigations into the protective efficacy of these vaccines in animal models. This technology has been acquired by GSK which is leading several clinical trials. In addition, the laboratory is pursuing other vaccine targets, including Staphylococcus aureus, Mycobacterium tuberculosis, Group B Streptococcus, and Salmonella and Shigella species.
Mechanistic studies
Beyond vaccine development, the laboratory uses different vaccine approaches, including the MAPS platform, as a research tool to understand the basic principle of the activation of the immune system and the clearance or neutralization of bacteria. The laboratory aims to explore how the immune system responds differentially to various antigens and understand the underlying mechanisms. This involves evaluating the effects of various chemical, physical, and molecular properties of antigens in activating antibody and cellular immune responses. Additionally, the laboratory seeks to illustrate how humoral and cellular immunity protects against different infections and how tissue-resident immune cells contribute to the protection.
Specific pathogens of interest to the laboratory
Streptococcus pneumoniae (S. pneumoniae)
This bacterium is a major cause of pneumonia, meningitis, and sepsis, particularly in children. The group’s research on S. pneumoniae has led to significant advancements in our understanding of the host factors influencing susceptibility to infection. We identified key mechanisms, such as Th17-mediated immune responses, in reducing and controlling mucosal colonization by S. pneumoniae. This work has opened new avenues for developing more effective vaccines and therapies against this important pathogen.
• Staphylococcus aureus (S. aureus): This ubiquitous bacterium is responsible for a wide range of skin and soft tissue infections, pneumonia, and even life-threatening bloodstream infections. The lab’s research has focused on uncovering novel antigens that may serve as potential vaccine targets. Mechanisms of immunity involving both conventional and unconventional T cells, are actively being explored. In particular, the role of tissue-resident T cells is being actively studied.
Mycobacterium tuberculosis (M. tuberculosis)
This bacterium is the causative agent of tuberculosis, a global health crisis claiming millions of lives each year. We have developed an innovative TB MAPS vaccine that has shown promise in animal models. Future work will seek to identify mechanisms of protection and defining a development vaccine candidate.
Salmonella typhi and paratyphi, other Salmonella and Shigella
These bacteria cause typhoidal syndrome, a debilitating illness prevalent in resource-limited settings, as well as invasive diseases and life-threatening diarrhea. Our research focuses on developing new vaccines and therapeutics against these pathogens.
Group B Streptococcus (GBS)
This organism is a major cause of morbidity and mortality in newborns. Using the MAPS platform, we have developed a multivalent vaccine, incorporating both polysaccharides and GBS-specific proteins, which induces excellent protection against invasive GBS disease in animal models.
Impact and future directions
Our research has enhanced our understanding of the immune response to various human pathogens and fostered the development of new vaccines, with the potential to save lives and improve global health outcomes.