Long-term protection against malaria after experimental sporozoite inoculation: An open-label follow-up study
Roestenberg M, Teirlinck AC, McCall MB, Teelen K, Makamdop KN, Wiersma J, Arens T, Beckers P, Van Gemert G, Van De Vegte-Bolmer M, Van Der Ven AJ, Luty AJ, Hermsen CC, Sauerwein RW (2011)
Publication Type: Journal article
Publication year: 2011
Journal
Book Volume: 377
Pages Range: 1770-1776
Journal Issue: 9779
DOI: 10.1016/S0140-6736(11)60360-7
Abstract
Background We have shown that immunity to infection with Plasmodium falciparum can be induced experimentally in malaria-naive volunteers through immunisation by bites of infected mosquitoes while simultaneously preventing disease with chloroquine prophylaxis. This immunity was associated with parasite-specifi c production of interferon ã and interleukin 2 by pluripotent eff ector memory cells in vitro. We aim to explore the persistence of protection and immune responses in the same volunteers. Methods In an open-label study at the Radboud University Nijmegen Medical Centre (Nijmegen, Netherlands), from November to December, 2009, we rechallenged previously immune volunteers (28 months after immunisation) with the bites of fi ve mosquitoes infected with P falciparum. Newly recruited malaria-naive volunteers served as infection controls. Our primary outcome was the detection of blood-stage parasitaemia by microscopy. We assessed the kinetics of parasitaemia with real-time quantitative PCR (rtPCR) and recorded clinical signs and symptoms. In-vitro production of interferon ã and interleukin 2 by eff ector memory T cells was studied after stimulation with sporozoites and red blood cells infected with P falciparum. Diff erences in cellular immune responses between the study groups were assessed with the Mann-Whitney test. This study is registered with ClinicalTrials.gov, number NCT00757887. Findings Four of six immune volunteers were microscopically negative after rechallenge. rtPCR-based detection of blood-stage parasites in these individuals was negative throughout follow-up. Patent parasitaemia was delayed in the remaining two immunised volunteers. In-vitro assays showed the long-term persistence of parasite-specifi c pluripotent eff ector memory T-cell responses in protected volunteers. The four protected volunteers reported several mild to moderate adverse events, of which the most commonly reported symptom was headache (one to three episodes per volunteer). The two patients with delayed patency had adverse events similar to those in the control group. Interpretation Artifi cially induced immunity lasts longer than generally recorded after natural exposure; providing a new avenue of research into the mechanisms of malaria immunity. © 2011 Elsevier Ltd.
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Netherlands (NL)How to cite
APA:
Roestenberg, M., Teirlinck, A.C., McCall, M.B., Teelen, K., Makamdop, K.N., Wiersma, J.,... Sauerwein, R.W. (2011). Long-term protection against malaria after experimental sporozoite inoculation: An open-label follow-up study. The Lancet, 377(9779), 1770-1776. https://doi.org/10.1016/S0140-6736(11)60360-7
MLA:
Roestenberg, Meta, et al. "Long-term protection against malaria after experimental sporozoite inoculation: An open-label follow-up study." The Lancet 377.9779 (2011): 1770-1776.
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