Experimental infection and protection against ... - TI Pharma
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Experimental infection and protection against ... - TI Pharma

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Chapter 10 Long-term protection against malaria after experimental sporozoite inoculation Meta Roestenberg 1 , Anne C. Teirlinck 1 , Matthew B.B. McCall 1 , Karina Teelen 1 , Krystelle Nganou Makamdop 1 , Jorien Wiersma 1 , Theo Arens 1 , Pieter Beckers 1 , GeertJan van Gemert 1 , Marga van de Vegte-Bolmer 1 , André J.A.M. van der Ven 2 , Adrian J.F. Luty 1 , Cornelus C. Hermsen 1 , Robert W. Sauerwein 1 1 Radboud University Nijmegen Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands 2 Radboud University Nijmegen Medical Centre, Department of Internal Medicine, Nijmegen, The Netherlands [A J A M van der Ven) Lancet 2011; 377:1770-1776

194 Chapter 10 Abstract Induction of long-lived immunity to Plasmodium falciparum (Pf) is a major obstacle to malaria vaccine development. Recently we showed that immunity to Pf can be induced experimentally in 10/10 of malaria-naïve volunteers through immunisation by bites of Pf-infected mosquitoes whilst simultaneously preventing disease by chloroquine prophylaxis. This immunity was associated with parasite-specific production of IFNγ and IL-2 by pluripotent effector memory cells in vitro. Here we explore the persistence of protection and immune responses in the same volunteers. In an open-label study conducted 28 months after immunisation, six previously immune volunteers were re-challenged by the bites of five Pf-infected mosquitoes. Five naive volunteers served as infection controls. The primary outcome was detection of blood-stage parasitemia by microscopy. The kinetics of parasitemia were assessed by real-time quantitative PCR (Q-PCR) and clinical signs and symptoms were recorded. In vitro production of IFNγ and IL-2 by effector memory T cells was studied following stimulation with sporozoites and Pf-infected red blood cells. This study is registered with clinicaltrials.gov, number NCT00757887. Four of six immune volunteers were fully protected against re-challenge. Q-PCRbased detection of blood-stage parasites in these individuals was negative throughout follow-up. Patency in the remaining two immunised volunteers was markedly delayed. In vitro assays revealed the long-term persistence of parasitespecific pluripotent effector memory T cell responses in protected volunteers. We demonstrate that immunity to Pf in human volunteers can persist for more than two years using an experimental immunisation protocol. Immunity was paralleled by maintenance of Pf-specific pluripotent effector memory T cells. These findings are unprecedented and demonstrate that artificially induced immunity may be longer-lasting than generally observed after natural exposure. These results open a novel avenue for research into mechanisms of malaria immunity.

Chapter 10<br />

Long-term <strong>protection</strong> <strong>against</strong> malaria after<br />

experimental sporozoite inoculation<br />

Meta Roestenberg 1 , Anne C. Teirlinck 1 , Matthew B.B. McCall 1 , Karina Teelen 1 ,<br />

Krystelle Nganou Makamdop 1 , Jorien Wiersma 1 , Theo Arens 1 , Pieter Beckers 1 ,<br />

GeertJan van Gemert 1 , Marga van de Vegte-Bolmer 1 , André J.A.M. van der Ven 2 ,<br />

Adrian J.F. Luty 1 , Cornelus C. Hermsen 1 , Robert W. Sauerwein 1<br />

1<br />

Radboud University Nijmegen Medical Centre, Department of Medical<br />

Microbiology, Nijmegen, The Netherl<strong>and</strong>s<br />

2<br />

Radboud University Nijmegen Medical Centre, Department of Internal<br />

Medicine, Nijmegen, The Netherl<strong>and</strong>s [A J A M van der Ven)<br />

Lancet 2011; 377:1770-1776

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