Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria
| Autor: | Elizabeth Nardin, Min Zhang, Victor Nussenzweig, Ramses Ayala, Vincent Sahi, Gabriel M. Gutierrez, Robert Mitchell, Xiangming Li, Amy R. Noe, Tiffany Tsao, Raquel Tayar Nogueira, Moriya Tsuji, Ruth S. Nussenzweig, Jordana Grazziela Coelho-dos-Reis, Jing Huang, James M. Wilson |
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| Rok vydání: | 2015 |
| Předmět: |
T cell
Immunology Protozoan Proteins Enzyme-Linked Immunosorbent Assay Mice Transgenic Mice Immune system Immunity Malaria Vaccines medicine Animals Humans Immunology and Allergy Malaria Falciparum B-cell activating factor biology Histocompatibility Antigens Class II Plasmodium falciparum biology.organism_classification Virology Immunity Humoral Circumsporozoite protein Disease Models Animal medicine.anatomical_structure Immunization Humoral immunity Heterografts |
| Zdroj: | Journal of Immunological Methods. 427:42-50 |
| ISSN: | 0022-1759 |
| DOI: | 10.1016/j.jim.2015.09.005 |
| Popis: | In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-γ and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen. |
| Databáze: | OpenAIRE |
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