Vi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever
Vi-polysaccharide conjugate vaccines are efficacious against cases of typhoid fever; however, an absolute correlate of protection is not established. In this study, we investigated the leukocyte response to a Vi-tetanus toxoid conjugate vaccine (Vi-TT) in comparison with a plain polysaccharide vacci...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Frontiers Media
2020
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| _version_ | 1797075670625419264 |
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| author | Cross, DL Verheul, MK Leipold, MD Obermoser, G Jin, C Jones, E Starr, JS Mohorianu, I Blohmke, CJ Maecker, HT Napolitani, G Hill, J Pollard, AJ |
| author_facet | Cross, DL Verheul, MK Leipold, MD Obermoser, G Jin, C Jones, E Starr, JS Mohorianu, I Blohmke, CJ Maecker, HT Napolitani, G Hill, J Pollard, AJ |
| author_sort | Cross, DL |
| collection | OXFORD |
| description | Vi-polysaccharide conjugate vaccines are efficacious against cases of typhoid fever; however, an absolute correlate of protection is not established. In this study, we investigated the leukocyte response to a Vi-tetanus toxoid conjugate vaccine (Vi-TT) in comparison with a plain polysaccharide vaccine (Vi-PS) in healthy adults subsequently challenged with Salmonella Typhi. Immunological responses and their association with challenge outcome was assessed by mass cytometry and Vi-ELISpot assay. Immunization induced significant expansion of plasma cells in both vaccines with modest T follicular helper cell responses detectable after Vi-TT only. The Vi-specific IgG and IgM B cell response was considerably greater in magnitude in Vi-TT recipients. Intriguingly, a significant increase in a subset of IgA+ plasma cells expressing mucosal migratory markers α4β7 and CCR10 was observed in both vaccine groups, suggesting a gut-tropic, mucosal response is induced by Vi-vaccination. The total plasma cell response was significantly associated with protection against typhoid fever in Vi-TT vaccinees but not Vi-PS. IgA+ plasma cells were not significantly associated with protection for either vaccine, although a trend is seen for Vi-PS. Conversely, the IgA- fraction of the plasma cell response was only associated with protection in Vi-TT. In summary, these data indicate that a phenotypically heterogeneous response including both gut-homing and systemic antibody secreting cells may be critical for protection induced by Vi-TT vaccination. |
| first_indexed | 2024-03-06T23:53:32Z |
| format | Journal article |
| id | oxford-uuid:73716b6b-e23d-442b-9783-628ac9a3ca56 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:53:32Z |
| publishDate | 2020 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:73716b6b-e23d-442b-9783-628ac9a3ca562022-03-26T19:56:22ZVi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid feverJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:73716b6b-e23d-442b-9783-628ac9a3ca56EnglishSymplectic ElementsFrontiers Media2020Cross, DLVerheul, MKLeipold, MDObermoser, GJin, CJones, EStarr, JSMohorianu, IBlohmke, CJMaecker, HTNapolitani, GHill, JPollard, AJVi-polysaccharide conjugate vaccines are efficacious against cases of typhoid fever; however, an absolute correlate of protection is not established. In this study, we investigated the leukocyte response to a Vi-tetanus toxoid conjugate vaccine (Vi-TT) in comparison with a plain polysaccharide vaccine (Vi-PS) in healthy adults subsequently challenged with Salmonella Typhi. Immunological responses and their association with challenge outcome was assessed by mass cytometry and Vi-ELISpot assay. Immunization induced significant expansion of plasma cells in both vaccines with modest T follicular helper cell responses detectable after Vi-TT only. The Vi-specific IgG and IgM B cell response was considerably greater in magnitude in Vi-TT recipients. Intriguingly, a significant increase in a subset of IgA+ plasma cells expressing mucosal migratory markers α4β7 and CCR10 was observed in both vaccine groups, suggesting a gut-tropic, mucosal response is induced by Vi-vaccination. The total plasma cell response was significantly associated with protection against typhoid fever in Vi-TT vaccinees but not Vi-PS. IgA+ plasma cells were not significantly associated with protection for either vaccine, although a trend is seen for Vi-PS. Conversely, the IgA- fraction of the plasma cell response was only associated with protection in Vi-TT. In summary, these data indicate that a phenotypically heterogeneous response including both gut-homing and systemic antibody secreting cells may be critical for protection induced by Vi-TT vaccination. |
| spellingShingle | Cross, DL Verheul, MK Leipold, MD Obermoser, G Jin, C Jones, E Starr, JS Mohorianu, I Blohmke, CJ Maecker, HT Napolitani, G Hill, J Pollard, AJ Vi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever |
| title | Vi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever |
| title_full | Vi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever |
| title_fullStr | Vi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever |
| title_full_unstemmed | Vi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever |
| title_short | Vi-vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever |
| title_sort | vi vaccinations include heterogeneous plasma cell responses that associate with protection from typhoid fever |
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