ChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humans
The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Journal article |
| Publicado em: |
2012
|
| _version_ | 1826284065172488192 |
|---|---|
| author | Sheehy, S Duncan, C Elias, S Choudhary, P Biswas, S Halstead, F Collins, K Edwards, N Douglas, A Anagnostou, N Ewer, K Havelock, T Havelock, T Mahungu, T Bliss, C Miura, K Poulton, I Lillie, P Antrobus, R Berrie, E Moyle, S Gantlett, K Colloca, S Colloca, S Cortese, R |
| author_facet | Sheehy, S Duncan, C Elias, S Choudhary, P Biswas, S Halstead, F Collins, K Edwards, N Douglas, A Anagnostou, N Ewer, K Havelock, T Havelock, T Mahungu, T Bliss, C Miura, K Poulton, I Lillie, P Antrobus, R Berrie, E Moyle, S Gantlett, K Colloca, S Colloca, S Cortese, R |
| author_sort | Sheehy, S |
| collection | OXFORD |
| description | The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1AMA1 - results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets. © The American Society of Gene and Cell Therapy. |
| first_indexed | 2024-03-07T01:08:15Z |
| format | Journal article |
| id | oxford-uuid:8c183715-30a7-4819-a45c-1e3a738e8d6c |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:08:15Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:8c183715-30a7-4819-a45c-1e3a738e8d6c2022-03-26T22:42:26ZChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humansJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8c183715-30a7-4819-a45c-1e3a738e8d6cSymplectic Elements at Oxford2012Sheehy, SDuncan, CElias, SChoudhary, PBiswas, SHalstead, FCollins, KEdwards, NDouglas, AAnagnostou, NEwer, KHavelock, THavelock, TMahungu, TBliss, CMiura, KPoulton, ILillie, PAntrobus, RBerrie, EMoyle, SGantlett, KColloca, SColloca, SCortese, RThe induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1AMA1 - results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets. © The American Society of Gene and Cell Therapy. |
| spellingShingle | Sheehy, S Duncan, C Elias, S Choudhary, P Biswas, S Halstead, F Collins, K Edwards, N Douglas, A Anagnostou, N Ewer, K Havelock, T Havelock, T Mahungu, T Bliss, C Miura, K Poulton, I Lillie, P Antrobus, R Berrie, E Moyle, S Gantlett, K Colloca, S Colloca, S Cortese, R ChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humans |
| title | ChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humans |
| title_full | ChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humans |
| title_fullStr | ChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humans |
| title_full_unstemmed | ChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humans |
| title_short | ChAd63-MVA-vectored blood-stage Malaria vaccines targeting MSP1 and AMA1: Assessment of efficacy against mosquito bite challenge in humans |
| title_sort | chad63 mva vectored blood stage malaria vaccines targeting msp1 and ama1 assessment of efficacy against mosquito bite challenge in humans |
| work_keys_str_mv | AT sheehys chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT duncanc chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT eliass chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT choudharyp chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT biswass chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT halsteadf chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT collinsk chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT edwardsn chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT douglasa chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT anagnostoun chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT ewerk chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT havelockt chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT havelockt chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT mahungut chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT blissc chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT miurak chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT poultoni chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT lilliep chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT antrobusr chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT berriee chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT moyles chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT gantlettk chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT collocas chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT collocas chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans AT corteser chad63mvavectoredbloodstagemalariavaccinestargetingmsp1andama1assessmentofefficacyagainstmosquitobitechallengeinhumans |