Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria

J Immunol Methods. 2015 Dec;427:42-50. doi: 10.1016/j.jim.2015.09.005. Epub 2015 Sep 26.


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.

Keywords: HLA class II molecule; Human IgG; Human immune system mice; P. falciparum circumsporozoite protein; Protective anti-malaria immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Enzyme-Linked Immunosorbent Assay
  • Heterografts
  • Histocompatibility Antigens Class II
  • Humans
  • Immunity, Humoral / immunology*
  • Malaria Vaccines
  • Malaria, Falciparum / immunology*
  • Mice
  • Mice, Transgenic / immunology*
  • Protozoan Proteins / immunology


  • Histocompatibility Antigens Class II
  • Malaria Vaccines
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan