Priming of CD8+ T cell responses following immunization with heat-killed Plasmodium sporozoites.
Protective immune responses against malaria are induced by immunization with radiation-attenuated Plasmodium sporozoites. In contrast, non-viable, heat-killed sporozoites do not induce protection, emphasizing the requirement for live parasites to achieve effective immune responses. Using an experimental system with CD8+ T cells from T cell receptor-transgenic mice, we analyzed the primary CD8+ T cell responses elicited by heat-killed inactivated sporozoites. We found that the numbers of specific CD8+ T cells induced were much lower compared to when immunizing with attenuated sporozoites; however, the kinetics of activation and the phenotype of these T cells were similar in both groups. Despite their low frequency after priming, high numbers of specific CD8+ T cells were observed after boosting with a recombinant vaccinia virus. Upon induction of the recall response, the same level of protection was observed when either heat-killed or attenuated sporozoites were used for priming. We propose that live parasites are not critical for the induction of memory T cell populations against the malaria liver stages.
Hafalla
Julius C R
JC
Department of Medical Parasitology, New York University School of Medicine, New York 10010, USA.
Rai
Urvashi
U
Morrot
Alexandre
A
Bernal-Rubio
Dabeiba
D
Zavala
Fidel
F
Rodriguez
Ana
A
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018960:Hyaluronan Receptors / Q000032:analysis; D007114:Immunization; D016130:Immunophenotyping; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
D018960:Hyaluronan Receptors; D017780:Malaria Vaccines; D015164:Vaccines, Inactivated