Protection Against a Malaria Challenge by Sporozoite Inoculation

N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.

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-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.)

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Anopheles / parasitology
  • Antibodies, Protozoan / blood
  • Antimalarials / therapeutic use
  • Biomarkers / blood
  • Blood / parasitology
  • Chloroquine / therapeutic use
  • Double-Blind Method
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Malaria Vaccines* / adverse effects
  • Malaria Vaccines* / immunology
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / prevention & control*
  • Parasitemia
  • Plasmodium falciparum* / immunology
  • Plasmodium falciparum* / isolation & purification
  • Sporozoites / immunology*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Young Adult

Substances

  • Antibodies, Protozoan
  • Antimalarials
  • Biomarkers
  • Interleukin-2
  • Malaria Vaccines
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Chloroquine

Associated data

  • ClinicalTrials.gov/NCT00442377