Protection against a Malaria Challenge by Sporozoite Inoculation.

作者：Roestenberg Meta; McCall Matthew; Hopman Joost; Wiersma Jorien; Luty Adrian J F; van Gemert Geert Jan; van de Vegte Bolmer Marga; van Schaijk Ben; Teelen Karina; Arens Theo; Spaarman Lopke; de Mast Quirijn; Roeffen Will; Snounou Georges; Renia Laurent; van der Ven Andre; Hermsen Cornelus C; Sauerwein Robert^*

来源：New England Journal of Medicine, 2009, 361(5): 468-477.

DOI：10.1056/NEJMoa0805832

Background: An effective vaccine for malaria is urgently needed. Naturally acquired immunity to malaria develops slowly, and induction of protection in humans can be achieved artificially by the inoculation of radiation-attenuated sporozoites by means of more than 1000 infective mosquito bites.
Methods: We exposed 15 healthy volunteers -- with 10 assigned to a vaccine group and 5 assigned to a control group -- to bites of mosquitoes once a month for 3 months while they were receiving a prophylactic regimen of chloroquine. The vaccine group was exposed to mosquitoes that were infected with Plasmodium falciparum, and the control group was exposed to mosquitoes that were not infected with the malaria parasite. One month after the discontinuation of chloroquine, protection was assessed by homologous challenge with five mosquitoes infected with P. falciparum. We assessed humoral and cellular responses before vaccination and before the challenge to investigate correlates of protection.
Results: All 10 subjects in the vaccine group were protected against a malaria challenge with the infected mosquitoes. In contrast, patent parasitemia (i.e., parasites found in the blood on microscopical examination) developed in all five control subjects. Adverse events were mainly reported by vaccinees after the first immunization and by control subjects after the challenge; no serious adverse events occurred. In this model, we identified the induction of parasite-specific pluripotent effector memory T cells producing interferon-(gamma), tumor necrosis factor (alpha), and interleukin-2 as a promising immunologic marker of protection.
Conclusions: Protection against a homologous malaria challenge can be induced by the inoculation of intact sporozoites. (ClinicalTrials.gov number, NCT00442377.)
N Engl J Med 2009;361:468-77.

• 出版日期2009-7-30