Yingjie Lu, PhD
|Hospital Title||Research Associate|
|Academic Title||Assistant Professor of Pediatrics|
300 Longwood Avenue
Boston MA 02115
Dr. Lu’s 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 his work on antigen discovery, Dr. Lu has also developed a novel strategy to induce protective IL-17A response through parenteral immunization. A fusion conjugate technology has been developed, which has the advantage of eliciting potent humoral and cellular responses. This fusion conjugate approachis based on the creation of a fusion of a candidate protein to the non-hemolytic, TLR4-activating mutant (W433F, D385N, and C428G) of pneumolysin (known as PdT), which is then conjugated to a polysaccharide of interest. This fusion conjugate construct not only enhances the antibody response to the polysaccharide and the protein, but also improves T cell response (including IL-17A and IFN-g)to the proteins. Using this technology, Dr Lu has developed 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. 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
Yingjie Lu received his Ph.D. in Biophysics at Tsinghua University, China. He completed postdoctoral fellowship training first in the Department of Infectious Diseases at St. Jude Children’s Hospital and then in the Division of Infectious Diseases at Children’s Hospital Boston, before becoming a faculty member in the Division of Infectious Diseases at Children’s in 2009.
- Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kolls J, Srivastava A, Forte S, Thompson C, Harney KF, Anderson PW, LIpsitch M and Malley R. Interleukin-17a mediates acquired immunity to pneumococcal colonization. PLoS pathogens. 4(9):e1000159, 2008.
- 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, Skovsted IC, Thompson CM, Anderson PW, Malley R. Mechanisms in the serotype-independent pneumococcal immunity induced in mice by intranasal vaccination with the cell wall polysaccharide. Microb Pathog. 47(3):177-82, 2009.
- 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.