title: Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver.
abstract: BACKGROUND
  The induction of sterile immunity and long lasting protection against malaria has been effectively achieved by immunization with sporozoites attenuated by gamma-irradiation or through deletion of genes. For mice immunized with radiation attenuated sporozoites (RAS) it has been shown that intrahepatic effector memory CD8+ T cells are critical for protection. Recent studies have shown that immunization with genetically attenuated parasites (GAP) in mice is also conferred by liver effector memory CD8+ T cells.
  
  
  RESULTS
  In this study we analysed effector memory cell responses after immunization of GAP that lack the P52 protein. We demonstrate that immunization with p52-GAP sporozoites also results in a strong increase of effector memory CD8+ T cells, even 6 months after immunization, whereas no specific CD4+ effector T cells response could be detected. In addition, we show that the increase of effector memory CD8+ T cells is specific for the liver and not for the spleen or lymph nodes.
  
  
  CONCLUSIONS
  These results indicate that immunization of mice with P. berghei p52-GAP results in immune responses that are comparable to those induced by RAS or GAP lacking expression of UIS3 or UIS4, with an important role implicated for intrahepatic effector memory CD8+ T cells. The knowledge of the mediators of protective immunity after immunization with different GAP is important for the further development of vaccines consisting of genetically attenuated sporozoites.
authors: Unidade de Malaria, Instituto de Medicina Molecular, Universidade de Lisboa, Av Professor Egas Moniz, Lisboa, 1649-028, Portugal. b.g.douradinha@gmail.com.
authors: Bruno
authors: B
authors: Douradinha
authors: Melissa
authors: M
authors: van Dijk
authors: Geert-Jan
authors: GJ
authors: van Gemert
authors: Shahid M
authors: SM
authors: Khan
authors: Chris J
authors: CJ
authors: Janse
authors: Andy P
authors: AP
authors: Waters
authors: Robert W
authors: RW
authors: Sauerwein
authors: Adrian Jf
authors: AJ
authors: Luty
authors: Bruno
authors: B
authors: Silva-Santos
authors: Maria M
authors: MM
authors: Mota
authors: Sabrina
authors: S
authors: Epiphanio