FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 361:468-477 July 30, 2009 Number 5 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Campbell, C. C. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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-, tumor necrosis factor , 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 [ClinicalTrials.gov] .)

Source Information

From the Departments of Medical Microbiology (M.R., M.M., J.H., J.W., A.J.F.L., G.J.G., M.V.-B., B.S., K.T., T.A., L.S., W.R., C.C.H., R.S.) and General Internal Medicine (Q.M., A.V.), Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; the Department of Parasitology, INSERM Unité 511, Hôpital Pitié–Salpêtrière, and the Université Pierre et Marie Curie — both in Paris (G.S.); and the Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Technology and Research, Biopolis, Singapore (L.R.).

Drs. Roestenberg and McCall contributed equally to this article.

Address reprint requests to Dr. Sauerwein at the Department of Medical Microbiology 268, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands, or at r.sauerwein{at}mmb.umcn.nl.

Full Text of this Article

This article has been cited by other articles:

• Varki, A., Gagneux, P. (2009). Human-specific evolution of sialic acid targets: Explaining the malignant malaria mystery?. Proc. Natl. Acad. Sci. USA 106: 14739-14740 [Full Text]  
• (2009). All you need to read in the other general journals. BMJ 339: b3144-b3144 [Full Text]  
• Campbell, C. C. (2009). Malaria Control -- Addressing Challenges to Ambitious Goals. NEJM 361: 522-523 [Full Text]  
• (2009). Immune Response to Sporozoite Inoculation by Mosquitoes. JWatch Infect. Diseases 2009: 2-2 [Full Text]