Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes
Summary: Antibodies targeting the NANP/NVDP repeat domain of the Plasmodium falciparum circumsporozoite protein (CSPRepeat) can protect against malaria. However, it has also been suggested that the CSPRepeat is a decoy that prevents the immune system from mounting responses against other domains of...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721003107 |
| _version_ | 1818958909813030912 |
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| author | Deepyan Chatterjee Fiona J. Lewis Henry J. Sutton Joe A. Kaczmarski Xin Gao Yeping Cai Hayley A. McNamara Colin J. Jackson Ian A. Cockburn |
| author_facet | Deepyan Chatterjee Fiona J. Lewis Henry J. Sutton Joe A. Kaczmarski Xin Gao Yeping Cai Hayley A. McNamara Colin J. Jackson Ian A. Cockburn |
| author_sort | Deepyan Chatterjee |
| collection | DOAJ |
| description | Summary: Antibodies targeting the NANP/NVDP repeat domain of the Plasmodium falciparum circumsporozoite protein (CSPRepeat) can protect against malaria. However, it has also been suggested that the CSPRepeat is a decoy that prevents the immune system from mounting responses against other domains of CSP. Here, we show that, following parasite immunization, B cell responses to the CSPRepeat are immunodominant over responses to other CSP domains despite the presence of similar numbers of naive B cells able to bind these regions. We find that this immunodominance is driven by avid binding of the CSPRepeat to cognate B cells that are able to expand at the expense of B cells with other specificities. We further show that mice immunized with repeat-truncated CSP molecules develop responses to subdominant epitopes and are protected against malaria. These data demonstrate that the CSPRepeat functions as a decoy, but truncated CSP molecules may be an approach for malaria vaccination. |
| first_indexed | 2024-12-20T11:33:14Z |
| format | Article |
| id | doaj.art-eb8c6165353a47159a075cd23c40ac5d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T11:33:14Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-eb8c6165353a47159a075cd23c40ac5d2022-12-21T19:42:13ZengElsevierCell Reports2211-12472021-04-01352108996Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopesDeepyan Chatterjee0Fiona J. Lewis1Henry J. Sutton2Joe A. Kaczmarski3Xin Gao4Yeping Cai5Hayley A. McNamara6Colin J. Jackson7Ian A. Cockburn8Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaResearch School of Chemistry, The Australian National University, Canberra, ACT 2601, AustraliaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaResearch School of Chemistry, The Australian National University, Canberra, ACT 2601, AustraliaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia; Corresponding authorSummary: Antibodies targeting the NANP/NVDP repeat domain of the Plasmodium falciparum circumsporozoite protein (CSPRepeat) can protect against malaria. However, it has also been suggested that the CSPRepeat is a decoy that prevents the immune system from mounting responses against other domains of CSP. Here, we show that, following parasite immunization, B cell responses to the CSPRepeat are immunodominant over responses to other CSP domains despite the presence of similar numbers of naive B cells able to bind these regions. We find that this immunodominance is driven by avid binding of the CSPRepeat to cognate B cells that are able to expand at the expense of B cells with other specificities. We further show that mice immunized with repeat-truncated CSP molecules develop responses to subdominant epitopes and are protected against malaria. These data demonstrate that the CSPRepeat functions as a decoy, but truncated CSP molecules may be an approach for malaria vaccination.http://www.sciencedirect.com/science/article/pii/S2211124721003107immunodominanceB cellsmalariaPlasmodium falciparummalaria vaccinescircumsporozoite protein |
| spellingShingle | Deepyan Chatterjee Fiona J. Lewis Henry J. Sutton Joe A. Kaczmarski Xin Gao Yeping Cai Hayley A. McNamara Colin J. Jackson Ian A. Cockburn Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes Cell Reports immunodominance B cells malaria Plasmodium falciparum malaria vaccines circumsporozoite protein |
| title | Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes |
| title_full | Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes |
| title_fullStr | Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes |
| title_full_unstemmed | Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes |
| title_short | Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes |
| title_sort | avid binding by b cells to the plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes |
| topic | immunodominance B cells malaria Plasmodium falciparum malaria vaccines circumsporozoite protein |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721003107 |
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