Human CD8+ T cells mediate protective immunity induced by a human malaria vaccine in human immune system mice

Vaccine. 2016 Aug 31;34(38):4501-4506. doi: 10.1016/j.vaccine.2016.08.006. Epub 2016 Aug 5.

Abstract

A number of studies have shown that CD8+ T cells mediate protective anti-malaria immunity in a mouse model. However, whether human CD8+ T cells play a role in protection against malaria remains unknown. We recently established human immune system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by transduction with HLA-A∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. These HIS-CD8 mice mount a potent, antigen-specific HLA-A∗0201-restricted human CD8+ T-cell response upon immunization with a recombinant adenovirus expressing a human malaria antigen, the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP. In the present study, we challenged AdPfCSP-immunized HIS-CD8 mice with transgenic Plasmodium berghei sporozoites expressing full-length PfCSP and found that AdPfCSP-immunized (but not naïve) mice were protected against subsequent malaria challenge. The level of the HLA-A∗0201-restricted, PfCSP-specific human CD8+ T-cell response was closely correlated with the level of malaria protection. Furthermore, depletion of human CD8+ T cells from AdPfCSP-immunized HIS-CD8 mice almost completely abolished the anti-malaria immune response. Taken together, our data show that human CD8+ T cells mediate protective anti-malaria immunity in vivo.

Keywords: Human CD8+ T cell; Human immune system mice; Malaria; Protection; Recombinant adenovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Dependovirus
  • Genetic Vectors
  • HLA-A2 Antigen / genetics
  • Humans
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / prevention & control*
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Plasmodium falciparum
  • Protozoan Proteins / immunology
  • Sporozoites

Substances

  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Malaria Vaccines
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan