The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody

Alexander D. Douglas (), Andrew R. Williams, Joseph J. Illingworth, Gathoni Kamuyu, Sumi Biswas, Anna L. Goodman, David H. Wyllie, Cécile Crosnier, Kazutoyo Miura, Gavin J. Wright, Carole A. Long, Faith H. Osier, Kevin Marsh, Alison V. Turner, Adrian V.S. Hill and Simon J. Draper
Additional contact information
Alexander D. Douglas: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
Andrew R. Williams: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
Joseph J. Illingworth: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
Gathoni Kamuyu: KEMRI Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108
Sumi Biswas: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
Anna L. Goodman: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
David H. Wyllie: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
Cécile Crosnier: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton
Kazutoyo Miura: Laboratory of Malaria and Vector Research, NIAID/NIH, 12735 Twinbrook Parkway, Twinbrook 3, Rockville, Maryland 20852, USA.
Gavin J. Wright: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton
Carole A. Long: Laboratory of Malaria and Vector Research, NIAID/NIH, 12735 Twinbrook Parkway, Twinbrook 3, Rockville, Maryland 20852, USA.
Faith H. Osier: KEMRI Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108
Kevin Marsh: KEMRI Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108
Alison V. Turner: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
Adrian V.S. Hill: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive
Simon J. Draper: Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive

Nature Communications, 2011, vol. 2, issue 1, 1-9

Abstract: Abstract Current vaccine strategies against the asexual blood stage of Plasmodium falciparum are mostly focused on well-studied merozoite antigens that induce immune responses after natural exposure, but have yet to induce robust protection in any clinical trial. Here we compare human-compatible viral-vectored vaccines targeting ten different blood-stage antigens. We show that the full-length P. falciparum reticulocyte-binding protein homologue 5 (PfRH5) is highly susceptible to cross-strain neutralizing vaccine-induced antibodies, out-performing all other antigens delivered by the same vaccine platform. We find that, despite being susceptible to antibody, PfRH5 is unlikely to be under substantial immune selection pressure; there is minimal acquisition of anti-PfRH5 IgG antibodies in malaria-exposed Kenyans. These data challenge the widespread beliefs that any merozoite antigen that is highly susceptible to immune attack would be subject to significant levels of antigenic polymorphism, and that erythrocyte invasion by P. falciparum is a degenerate process involving a series of parallel redundant pathways.

Date: 2011
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DOI: 10.1038/ncomms1615

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