Sandra P. Chang, Ph.D.
Department of Tropical Medicine, Medical Microbiology and Pharmacology
John A. Burns School of Medicine
Office: JABSOM BSB 320H
Email: sandrac [at] hawaii.edu
||(Biology) University of Hawai‘i at Manoa, Honolulu, Hawai‘i
||(Microbiology) University of Hawai‘i at Manoa, Honolulu, Hawai‘i
||(Microbiology and Immunology) Oregon Health Sciences University, Portland, Oregon
1983-1986 Post-doc (Molecular Biology) California Institute of Technology, Pasadena, California
1986-1988 Assistant Researcher, Department of Tropical Medicine and Medical Microbiology, John A. Burns School of Medicine, University of Hawaii
1988 1995 Associate Researcher, Department of Tropical Medicine and Medical Microbiology, John A. Burns School of Medicine, University of Hawaii
1995-1997 Associate Professor, Department of Tropical Medicine and Medical Microbiology, John A. Burns School of Medicine, University of Hawaii
1997-present Professor, Department of Tropical Medicine and Medical Microbiology, John A. Burns School of Medicine, University of Hawaii
Research Keywords: Malaria, vaccine, adjuvants
Malaria Immunity & Vaccine Development
Malaria is a major cause of global morbidity and mortality in tropical countries and most notably among infants, young children and pregnant women in sub-Saharan Africa. Our long term goal is to develop a safe and effective blood stage vaccine directed against merozoite surface protein-1 (MSP1), a major coat protein of P. falciparum merozoites. This goal requires development of two essential components of a malaria vaccine, (i) the production of an optimally immunogenic antigen capable of inducing a protective immune response, and (ii) the identification of an immunostimulatory and non-toxic adjuvant formulation that may be combined with this antigen to generate protective immunity to falciparum malaria. Previous studies in this laboratory have focused on developing a baculovirus recombinant 42 kDa MSP1 C-terminal polypeptide which is highly immunogenic and induces protection in a non-human primate model of P. falciparum malaria. One of our current research objectives is to improve the protective immune response to a P. falciparum MSP1-based malaria vaccine by combining sequences located within MSP1 blocks 4, 16, and 17 to induce protective immune responses to multiple MSP1 epitopes. Our second research objective is to evaluate the ability of a series of well-defined immunomodulators to stimulate an immune response to MSP1 with in vitro and in vivo biological activities against P. falciparum blood stages. We hypothesize that a multi-epitope MSP1 antigen formulated with specific combinations of TLR (Toll-like receptor) and NOD (nucleotide-binding oligomerization domain-like receptor) agonists will be effective in inducing a protective immune response to P. falciparum infection.
The current COBRE Pilot and Bridging Fund project has one specific aim:
Specific Aim 1
- Determine whether combinations of PRR agonists that utilize different intracellular signaling pathways can drive the differentiation of conventional and plasmacytoid dendritic cells as determined by induction of cell surface activation receptors and cytokines associated with Th cell differentiation.
- Hypothesis: Specific combinations of pattern-recognition receptor (PRR) agonists will be effective in inducing a potent and protective immune response to the P. falciparum blood stage antigen, merozoite surface protein-1, through optimal dendritic cell activation.
- Rationale: PRRs play an important role in dendritic cell activation and can influence the quality of the adaptive immune response. Ligands that trigger PRRs utilizing distinct intracellular signaling pathways may lead to synergistic activation of dendritic cells and influence the polarization of T helper phenotypes.
- Experimental Plan: We will examine RNA transcription and protein expression of bone marrow-derived DCs stimulated in vitro with various individual and combinations of PRR ligands that utilize distinct intracellular signaling pathways for DC activation. This strategy will allow us to identify combinations of PRR ligands that synergize to activate DCs to express cell surface markers and cytokines associated with polarization of the immune response to a Th1 response, a Th2 response, or a mixed Th1/Th2 response. In future studies, these combinations will be evaluated in vivo as adjuvants in the immune response to malaria vaccine antigens.
Sana TR, Gordon DB, Fischer SM, Tichy SE, Kitagawa N, Lai C, Gosnell WL, Chang SP.
Global mass spectrometry based metabolomics profiling of erythrocytes infected with Plasmodium falciparum.
Chang SP, Kayatani AK, Terrientes ZI, Herrera S, Leke RG, Taylor DW.
Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4.
Lau OS, Ng DW, Chan WW, Chang SP, Sun SS.
Production of the 42-kDa fragment of Plasmodium falciparum merozoite surface protein 1, a leading malaria vaccine antigen, in Arabidopsis thaliana seeds.
Plant Biotechnology Journal
Reed ZH, Kieny MP, Engers H, Friede M, Chang S, Longacre S, Malhotra P, Pan W, Long C.
Comparison of immunogenicity of five MSP1-based malaria vaccine candidate antigens in rabbits.
Terrientes ZI, Vergara J, Kramer K, Herrera S, Chang SP.
Restricted genetic diversity of Plasmodium falciparum major merozoite surface protein 1 in isolates from Colombia.
American Journal of Tropical Medicine and Hygiene
Grant No / Title: 0 / Improve Long-term Immunity to Childhood Pertussis Vaccination
Status / Agency: Awarded / Chun Foundation
Start Date / End Date: 12 June 2015 / 15 August 2016