Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells
AUTOR(ES)
van Dijk, Melissa R.
FONTE
National Academy of Sciences
RESUMO
Immunization with Plasmodium sporozoites that have been attenuated by γ-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked by infected hepatocytes cells that contain long-lived, partially developed parasites. Here we analyzed sporozoites of Plasmodium berghei that are deficient in P36p (p36p-), a member of the P48/45 family of surface proteins. P36p plays no role in the ability of sporozoites to infect and traverse hepatocytes, but p36p- sporozoites abort during development within the hepatocyte. Immunization with p36p- sporozoites results in a protective immunity against subsequent challenge with infectious wild-type sporozoites, another example of a specifically genetically attenuated sporozoite (GAS) conferring protective immunity. Comparison of biological characteristics of p36p- sporozoites with radiation-attenuated sporozoites demonstrates that liver cells infected with p36p- sporozoites disappear rapidly as a result of apoptosis of host cells that may potentiate the immune response. Such knowledge of the biological characteristics of GAS and their evoked immune responses are essential for further investigation of the utility of an optimized GAS-based malaria vaccine.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1189305Documentos Relacionados
- Survival and antigenic profile of irradiated malarial sporozoites in infected liver cells.
- X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo
- Dendritic Cells Efficiently Induce Protective Antiviral Immunity
- p53-Mediated apoptosis is attenuated in Werner syndrome cells
- Characteristics of Virulent, Attenuated, and Avirulent Mycoplasma pneumoniae Strains