Roestenberg, M., McCall, M., Hopman, J., Wiersma, J., Luty, A. J. F., van Gemert, G. J., van de Vegte-Bolmer, M., van Schaijk, B., Teelen, K., Arens, T., et al. Protection against a malaria challenge by sporozoite inoculation. The New England Journal of Medicine 361, 468–477 (2009).
Abstract:
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-γ, tumor necrosis factor α, 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.)