Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine
Efforts are currently underway to improve the efficacy of sub-unit malaria vaccines through assessment of new adjuvants, vaccination platforms and antigens. In this study, we further assess the antigen P. falciparum (Pf) upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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American Society for Microbiology
2016
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| _version_ | 1797058298562740224 |
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| author | Longley, R Halbroth, B Salman, A Ewer, K Hodgson, S Janse, C Khan, S Hill, A Spencer, A |
| author_facet | Longley, R Halbroth, B Salman, A Ewer, K Hodgson, S Janse, C Khan, S Hill, A Spencer, A |
| author_sort | Longley, R |
| collection | OXFORD |
| description | Efforts are currently underway to improve the efficacy of sub-unit malaria vaccines through assessment of new adjuvants, vaccination platforms and antigens. In this study, we further assess the antigen P. falciparum (Pf) upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P. berghei (Pb) parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild type Pb parasites. We also show that PfUIS3-specific cellular memory responses can be recalled in human volunteers exposed to Pf parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was co-administered with the vaccine candidate ChAd63-MVA Pf thrombospondin-related adhesion protein (TRAP), there was no significant change in immunogenicity to either vaccine. However, when these mice were challenged with double chimeric Pb-Pf parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was only evident when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitaemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild type Pb; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced. |
| first_indexed | 2024-03-06T19:48:29Z |
| format | Journal article |
| id | oxford-uuid:23288ee8-9b62-453c-bc7f-6152a96a9912 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:48:29Z |
| publishDate | 2016 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:23288ee8-9b62-453c-bc7f-6152a96a99122022-03-26T11:42:46ZAssessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccineJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:23288ee8-9b62-453c-bc7f-6152a96a9912EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2016Longley, RHalbroth, BSalman, AEwer, KHodgson, SJanse, CKhan, SHill, ASpencer, AEfforts are currently underway to improve the efficacy of sub-unit malaria vaccines through assessment of new adjuvants, vaccination platforms and antigens. In this study, we further assess the antigen P. falciparum (Pf) upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P. berghei (Pb) parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild type Pb parasites. We also show that PfUIS3-specific cellular memory responses can be recalled in human volunteers exposed to Pf parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was co-administered with the vaccine candidate ChAd63-MVA Pf thrombospondin-related adhesion protein (TRAP), there was no significant change in immunogenicity to either vaccine. However, when these mice were challenged with double chimeric Pb-Pf parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was only evident when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitaemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild type Pb; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced. |
| spellingShingle | Longley, R Halbroth, B Salman, A Ewer, K Hodgson, S Janse, C Khan, S Hill, A Spencer, A Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine |
| title | Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine |
| title_full | Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine |
| title_fullStr | Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine |
| title_full_unstemmed | Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine |
| title_short | Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine |
| title_sort | assessment of the plasmodium falciparum pre erythrocytic antigen uis3 as a potential candidate for a malaria vaccine |
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