My research focuses on the study of pathogenesis and vaccine development for two important pediatric pathogens, Streptococcus pneumoniae and Salmonella typhi.
Two arms of the adaptive immune system, antibody and CD4+ IL-17A producing T-cells, are important for protection against pneumococcal disease and colonization. Antigens that can induce either or both arms of immunity are being characterized in the laboratory using chromatographic technologies or novel reverse-vaccinology methods. Using these methods, several conserved antigens with protective potential against colonization and/or sepsis were identified. Further characterization of these antigens is an active area of research in the laboratory.
In addition to my work on antigen discovery, I am also interested in developing strategies to induce protective IL-17A response through parenteral immunization and the mechanism study for such constructs. A fusion conjugate technology has been developed, which has the advantage of eliciting potent humoral and cellular responses. A candidate vaccine consisting of conserved pneumococcal antigens which are fused with PdT and then conjugated to the extracellular capsular Vi polysaccharide of Salmonella Typhi has been developed. In preclinical studies, this candidate vaccine elicits potent immune responses against S. pneumoniae and S. typhi and also confers impressive protection against pneumococcal colonization and sepsis. Further preclinical work on this candidate vaccine is ongoing.
About Yingjie Lu
- Lu YJ, Forte S, Thompson C, Anderson PW and Malley R. Protection against pneumococcal colonization and fatal pneumonia by a trivalent conjugate of a fusion protein with the cell wall polysaccharide. Infection and Immunity 77(5):2076-83, 2009.
- Lu YJ, Yadav P, Clements JD, Forte S, Srivastava A, Thompson CM, Seid R, Look J, Alderson M, Tate A, Maisonneuve JF, Robertson G, Anderson PW, Malley R. Options for inactivation, adjuvant, and route of topical administration of a killed, unencapsulated pneumococcal whole-cell vaccine. Clinical Vaccine Immunology. 17(6):1005-12, 2010
- Lu YJ, Leite L, Gonçalves VM, Dias WD, Liberman C, Fratelli F, Alderson M, Tate A, Maisonneuve JF, Robertson G, Graca R, Sayeed S, Thompson CM, Anderson P, Malley R. GMP-grade Pneumococcal Whole-cell Vaccine Injected Subcutaneously Protects Mice from Nasopharyngeal Colonization and Fatal Aspiration-sepsis. Vaccine 28(47):7468, 2010
- Lu YJ, Zhang F, Sayeed S, Thompson C, Szu S, Schneerson R, Robbins J, Anderson PW and Malley R. A Bivalent Vaccine to Protect against Streptococcus pneumoniae and Salmonella typhi. Vaccine. 30(23): 3405-3412, 2012
- Moffitt KL, Malley R*, Lu YJ*. Identification of protective pneumococcal T(h)17 antigens from the soluble fraction of a killed whole cell vaccine. PLoS One. 7(8):e43445, 2012
- Zhang F, Lu YJ*, Malley R*. A multiple antigen presenting system (MAPS) to induce comprehensive B- and T-cell immunity. Proc Natl Acad Sci. 2013 110(33):13564-9
* Contributed equally