Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine
The leading malaria vaccine in development is the circumsporozoite (CS) protein-based vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy largely mediated by CS specific antibodies. We aimed to enhance vaccine e...
| Main Authors: | , , , , |
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| Format: | Journal article |
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Nature Publishing Group
2017
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| _version_ | 1797105207533895680 |
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| author | Gilbert, S Collins, K Snaith, R Cottingham, M Hill, A |
| author_facet | Gilbert, S Collins, K Snaith, R Cottingham, M Hill, A |
| author_sort | Gilbert, S |
| collection | OXFORD |
| description | The leading malaria vaccine in development is the circumsporozoite (CS) protein-based vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy largely mediated by CS specific antibodies. We aimed to enhance vaccine efficacy by generating a potentially more immunogenic CS-based particle vaccine and developed a next-generation RTS,S-like vaccine, called R21. The major improvement is that in contrast to RTS,S, R21 particles are formed from a single CS-HBsAg fusion protein and this leads to a vaccine composed of a much higher proportion of CS antigen than RTS,S. We demonstrate that in BALB/c mice R21 is immunogenic at very low doses and when administered with the ISCOM adjuvants Abisco-100 and Matrix-M it elicits sterile protection against transgenic sporozoite challenge. In addition, in contrast to RTS,S, only a minimal antibody response to the HBsAg carrier was induced. Concurrent induction of cellular and humoral immune responses was also achieved by combining R21 with TRAP-based viral vectors and protective efficacy was significantly enhanced. These studies identify an anti-sporozoite vaccine component that may outperform RTS,S and R21 is now under evaluation in Phase 1/2a clinical trials. |
| first_indexed | 2024-03-07T06:44:11Z |
| format | Journal article |
| id | oxford-uuid:fa5080e4-b03e-4170-a0fd-4f2a626cd908 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:44:11Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:fa5080e4-b03e-4170-a0fd-4f2a626cd9082022-03-27T13:04:47ZEnhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccineJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fa5080e4-b03e-4170-a0fd-4f2a626cd908Symplectic Elements at OxfordNature Publishing Group2017Gilbert, SCollins, KSnaith, RCottingham, MHill, AThe leading malaria vaccine in development is the circumsporozoite (CS) protein-based vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy largely mediated by CS specific antibodies. We aimed to enhance vaccine efficacy by generating a potentially more immunogenic CS-based particle vaccine and developed a next-generation RTS,S-like vaccine, called R21. The major improvement is that in contrast to RTS,S, R21 particles are formed from a single CS-HBsAg fusion protein and this leads to a vaccine composed of a much higher proportion of CS antigen than RTS,S. We demonstrate that in BALB/c mice R21 is immunogenic at very low doses and when administered with the ISCOM adjuvants Abisco-100 and Matrix-M it elicits sterile protection against transgenic sporozoite challenge. In addition, in contrast to RTS,S, only a minimal antibody response to the HBsAg carrier was induced. Concurrent induction of cellular and humoral immune responses was also achieved by combining R21 with TRAP-based viral vectors and protective efficacy was significantly enhanced. These studies identify an anti-sporozoite vaccine component that may outperform RTS,S and R21 is now under evaluation in Phase 1/2a clinical trials. |
| spellingShingle | Gilbert, S Collins, K Snaith, R Cottingham, M Hill, A Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine |
| title | Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine |
| title_full | Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine |
| title_fullStr | Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine |
| title_full_unstemmed | Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine |
| title_short | Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine |
| title_sort | enhancing protective immunity to malaria with a highly immunogenic virus like particle vaccine |
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