التفاصيل البيبلوغرافية
| العنوان: |
Genetically attenuated Plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex Class I-dependent interferon-gamma-producing CD8+ T cells. |
| المؤلفون: |
Jobe O, Lumsden J, Mueller AK, Williams J, Silva-Rivera H, Kappe SH, Schwenk RJ, Matuschewski K, Krzych U, Jobe, Ousman, Lumsden, Joanne, Mueller, Ann-Kristin, Williams, Jackie, Silva-Rivera, Hilda, Kappe, Stefan H I, Schwenk, Robert J, Matuschewski, Kai, Krzych, Urszula |
| المصدر: |
Journal of Infectious Diseases; 8/15/2007, Vol. 196 Issue 4, p599-607, 9p |
| مصطلحات موضوعية: |
MALARIA prevention, ANIMAL experimentation, BLOOD proteins, CLINICAL drug trials, GLOBULINS, HISTOCOMPATIBILITY antigens, IMMUNITY, IMMUNIZATION, INTERFERONS, LIVER, MALARIA, MEDICAL protocols, MICE, GENETIC mutation, PROTOZOA, RESEARCH funding, T cells, VACCINES, SPORES |
| مستخلص: |
At present, radiation-attenuated plasmodia sporozoites ( gamma -spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, gamma -spz are not without risks. For example, the heterogeneity of the gamma -spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz. We evaluated the double-knockout Pbuis3(-)/4(-) parasites for protective efficacy and the contribution of CD8(+) T cells to protection. Pbuis3(-)/4(-) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8(+) T cells, given that mice deficient in beta (2)m were not protected. Pbuis3(-)/4(-) spz-immune CD8(+) T cells consisted of effector/memory phenotypes and produced interferon- gamma . On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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