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BMC Medicine
Published in: BMC Medicine 1/2018

Open Access 01-12-2018 | Research article

Vaccination with chemically attenuated Plasmodium falciparum asexual blood-stage parasites induces parasite-specific cellular immune responses in malaria-naïve volunteers: a pilot study

Authors: Danielle I. Stanisic, James Fink, Johanna Mayer, Sarah Coghill, Letitia Gore, Xue Q. Liu, Ibrahim El-Deeb, Ingrid B. Rodriguez, Jessica Powell, Nicole M. Willemsen, Sai Lata De, Mei-Fong Ho, Stephen L. Hoffman, John Gerrard, Michael F. Good

Published in: BMC Medicine | Issue 1/2018

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Abstract

Background

The continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4+ T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria.

Methods

In this current study, we evaluated the immunogenicity and safety of chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in eight malaria-naïve human volunteers. Study participants received a single dose of 3 × 107 Pf pRBC that had been treated in vitro with the cyclopropylpyrolloindole analogue, tafuramycin-A.

Results

We demonstrate that Pf asexual blood-stage parasites that are completely attenuated are immunogenic, safe and well tolerated in malaria-naïve volunteers. Following vaccination with a single dose, species and strain transcending Plasmodium-specific T cell responses were induced in recipients. This included induction of Plasmodium-specific lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN-γ and TNF, and CD3+CD45RO+ memory T cells. Pf-specific IgG was not detected.

Conclusions

This is the first clinical study evaluating a whole parasite blood-stage malaria vaccine. Following administration of a single dose of completely attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses were induced while Pf-specific antibodies were not detected. These results support further evaluation of this chemically attenuated vaccine in humans.

Trial registration

Trial registration: ACTRN12614000228​684. Registered 4 March 2014.
Appendix
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Metadata
Title
Vaccination with chemically attenuated Plasmodium falciparum asexual blood-stage parasites induces parasite-specific cellular immune responses in malaria-naïve volunteers: a pilot study
Authors
Danielle I. Stanisic
James Fink
Johanna Mayer
Sarah Coghill
Letitia Gore
Xue Q. Liu
Ibrahim El-Deeb
Ingrid B. Rodriguez
Jessica Powell
Nicole M. Willemsen
Sai Lata De
Mei-Fong Ho
Stephen L. Hoffman
John Gerrard
Michael F. Good
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2018
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-018-1173-9

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