Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study

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• 作者：Meta Roestenberg MD^a ; Anne C Teirlinck MSc^a ; Matthew BB McCall MD^a ; Karina Teelen BSc^a ; Krystelle Nganou Makamdop MSc^a ; Jorien Wiersma ADN^a ; Theo Arens BSc^a ; Pieter Beckers PhD^a ; GeertJan van Gemert BSc^a ; Marga van de Vegte-Bolmer BSc^a ; Prof André ; JAM van der Ven MD^b ; Adrian JF Luty PhD^a ; Cornelus C Hermsen PhD^a ; Prof Robert W Sauerwein MD^a ; ^{r.sauerwein@mmb.umcn.nl"" rel=""nofollow}
• 刊名：The Lancet
• 出版年：2011
• 出版时间：21 May 2011-27 May 2011
• 年：2011
• 卷：377
• 期：9779
• 页码：1770-1776
• 全文大小：372 K

文摘

Summary

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-specific production of interferon γ and interleukin 2 by pluripotent effector 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 five 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 γ and interleukin 2 by effector memory T cells was studied after stimulation with sporozoites and red blood cells infected with P falciparum. Differences 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-specific pluripotent effector 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

Artificially induced immunity lasts longer than generally recorded after natural exposure; providing a new avenue of research into the mechanisms of malaria immunity.

Funding

Dioraphte Foundation.