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

Alexander D Douglas; Andrew Richard 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; Simon J Draper

doi:10.1038/ncomms1615

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

Alexander D Douglas, Andrew Richard 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, Simon J Draper

166 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Communications
Vol/bind	2
Sider (fra-til)	601
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms1615
Status	Udgivet - 2011
Udgivet eksternt	Ja

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10.1038/ncomms1615

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Douglas, A. D., Williams, A. R., Illingworth, J. J., Kamuyu, G., Biswas, S., Goodman, A. L., Wyllie, D. H., Crosnier, C., Miura, K., Wright, G. J., Long, C. A., Osier, F. H., Marsh, K., Turner, A. V., Hill, A. V. S., & Draper, S. J. (2011). The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. Nature Communications, 2, 601. https://doi.org/10.1038/ncomms1615

Douglas, AD, Williams, AR, Illingworth, JJ, Kamuyu, G, Biswas, S, Goodman, AL, Wyllie, DH, Crosnier, C, Miura, K, Wright, GJ, Long, CA, Osier, FH, Marsh, K, Turner, AV, Hill, AVS & Draper, SJ 2011, 'The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody', Nature Communications, bind 2, s. 601. https://doi.org/10.1038/ncomms1615

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

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.",

author = "Douglas, {Alexander D} and Williams, {Andrew Richard} and Illingworth, {Joseph J} and Gathoni Kamuyu and Sumi Biswas and Goodman, {Anna L} and Wyllie, {David H} and C{\'e}cile Crosnier and Kazutoyo Miura and Wright, {Gavin J} and Long, {Carole A} and Osier, {Faith H} and Kevin Marsh and Turner, {Alison V} and Hill, {Adrian V S} and Draper, {Simon J}",

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doi = "10.1038/ncomms1615",

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T1 - The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody

AU - Douglas, Alexander D

AU - Williams, Andrew Richard

AU - Illingworth, Joseph J

AU - Kamuyu, Gathoni

AU - Biswas, Sumi

AU - Goodman, Anna L

AU - Wyllie, David H

AU - Crosnier, Cécile

AU - Miura, Kazutoyo

AU - Wright, Gavin J

AU - Long, Carole A

AU - Osier, Faith H

AU - Marsh, Kevin

AU - Turner, Alison V

AU - Hill, Adrian V S

AU - Draper, Simon J

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms1615

DO - 10.1038/ncomms1615

M3 - Journal article

C2 - 22186897

SN - 2041-1723

VL - 2

SP - 601

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

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