The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody.
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-vector...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1797104994541895680 |
|---|---|
| author | Douglas, A Williams, A Illingworth, J Kamuyu, G Biswas, S Goodman, A Wyllie, D Crosnier, C Miura, K Wright, G Long, C Osier, F Marsh, K Turner, A Hill, A Draper, S |
| author_facet | Douglas, A Williams, A Illingworth, J Kamuyu, G Biswas, S Goodman, A Wyllie, D Crosnier, C Miura, K Wright, G Long, C Osier, F Marsh, K Turner, A Hill, A Draper, S |
| author_sort | Douglas, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:41:17Z |
| format | Journal article |
| id | oxford-uuid:f95d7a97-545e-401a-98b0-28689b3f78f6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:41:17Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:f95d7a97-545e-401a-98b0-28689b3f78f62022-03-27T12:57:27ZThe blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f95d7a97-545e-401a-98b0-28689b3f78f6EnglishSymplectic Elements at Oxford2011Douglas, AWilliams, AIllingworth, JKamuyu, GBiswas, SGoodman, AWyllie, DCrosnier, CMiura, KWright, GLong, COsier, FMarsh, KTurner, AHill, ADraper, SCurrent 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. |
| spellingShingle | Douglas, A Williams, A Illingworth, J Kamuyu, G Biswas, S Goodman, A Wyllie, D Crosnier, C Miura, K Wright, G Long, C Osier, F Marsh, K Turner, A Hill, A Draper, S The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. |
| title | The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. |
| title_full | The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. |
| title_fullStr | The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. |
| title_full_unstemmed | The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. |
| title_short | The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. |
| title_sort | blood stage malaria antigen pfrh5 is susceptible to vaccine inducible cross strain neutralizing antibody |
| work_keys_str_mv | AT douglasa thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT williamsa thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT illingworthj thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT kamuyug thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT biswass thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT goodmana thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT wyllied thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT crosnierc thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT miurak thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT wrightg thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT longc thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT osierf thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT marshk thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT turnera thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT hilla thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT drapers thebloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT douglasa bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT williamsa bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT illingworthj bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT kamuyug bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT biswass bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT goodmana bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT wyllied bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT crosnierc bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT miurak bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT wrightg bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT longc bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT osierf bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT marshk bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT turnera bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT hilla bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody AT drapers bloodstagemalariaantigenpfrh5issusceptibletovaccineinduciblecrossstrainneutralizingantibody |