Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine
<p>Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01<sub>B</sub>-adjuvanted RH5.1 malaria antigen &...
| প্রধান লেখক: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
American Society for Clinical Investigation
2023
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| _version_ | 1826310740469874688 |
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| author | Nielsen, CM Barrett, JR Davis, C Fallon, JK Goh, C Michell, AR Griffin, C Kwok, A Loos, C Darko, S Laboune, F Tekman, M Diouf, A Miura, K Francica, JR Ransier, A Long, CA Silk, SE Payne, RO Minassian, AM Lauffenburger, DA Seder, RA Douek, DC Alter, G Draper, SJ |
| author_facet | Nielsen, CM Barrett, JR Davis, C Fallon, JK Goh, C Michell, AR Griffin, C Kwok, A Loos, C Darko, S Laboune, F Tekman, M Diouf, A Miura, K Francica, JR Ransier, A Long, CA Silk, SE Payne, RO Minassian, AM Lauffenburger, DA Seder, RA Douek, DC Alter, G Draper, SJ |
| author_sort | Nielsen, CM |
| collection | OXFORD |
| description | <p>Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01<sub>B</sub>-adjuvanted RH5.1 malaria antigen — substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.</p> |
| first_indexed | 2024-03-07T07:56:28Z |
| format | Journal article |
| id | oxford-uuid:af4bac7d-7fcf-432c-8efb-2a6edb4367f3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:56:28Z |
| publishDate | 2023 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | oxford-uuid:af4bac7d-7fcf-432c-8efb-2a6edb4367f32023-08-22T11:47:54ZDelayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccineJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:af4bac7d-7fcf-432c-8efb-2a6edb4367f3EnglishSymplectic ElementsAmerican Society for Clinical Investigation2023Nielsen, CMBarrett, JRDavis, CFallon, JKGoh, CMichell, ARGriffin, CKwok, ALoos, CDarko, SLaboune, FTekman, MDiouf, AMiura, KFrancica, JRRansier, ALong, CASilk, SEPayne, ROMinassian, AMLauffenburger, DASeder, RADouek, DCAlter, GDraper, SJ<p>Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01<sub>B</sub>-adjuvanted RH5.1 malaria antigen — substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.</p> |
| spellingShingle | Nielsen, CM Barrett, JR Davis, C Fallon, JK Goh, C Michell, AR Griffin, C Kwok, A Loos, C Darko, S Laboune, F Tekman, M Diouf, A Miura, K Francica, JR Ransier, A Long, CA Silk, SE Payne, RO Minassian, AM Lauffenburger, DA Seder, RA Douek, DC Alter, G Draper, SJ Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine |
| title | Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine |
| title_full | Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine |
| title_fullStr | Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine |
| title_full_unstemmed | Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine |
| title_short | Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine |
| title_sort | delayed boosting improves human antigen specific ig and b cell responses to the rh5 1 as01b malaria vaccine |
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