Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design
Gonorrhoea, caused by Neisseria gonorrhoeae, is a common sexually transmitted infection. Increasing multi-drug resistance and the impact of asymptomatic infections on sexual and reproductive health underline the need for an effective gonococcal vaccine. Outer membrane vesicles (OMVs) from Neisseria...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2024
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| _version_ | 1826315395693281280 |
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| author | Jones, RA Ramirez-Bencomo, F Whiting, G Fang, M Lavender, H Kurzyp, K Thistlethwaite, A Stejskal, L Rashmi, S Jerse, AE Cehovin, A Derrick, JP Tang, CM |
| author_facet | Jones, RA Ramirez-Bencomo, F Whiting, G Fang, M Lavender, H Kurzyp, K Thistlethwaite, A Stejskal, L Rashmi, S Jerse, AE Cehovin, A Derrick, JP Tang, CM |
| author_sort | Jones, RA |
| collection | OXFORD |
| description | Gonorrhoea, caused by Neisseria gonorrhoeae, is a common sexually transmitted infection. Increasing multi-drug resistance and the impact of asymptomatic infections on sexual and reproductive health underline the need for an effective gonococcal vaccine. Outer membrane vesicles (OMVs) from Neisseria meningitidis induce modest cross-protection against gonococcal infection. However, the presence of proteins in OMVs derived from N. gonorrhoeae that manipulate immune responses could hamper their success as a vaccine. Here we modified two key immunomodulatory proteins of the gonococcus; RmpM, which can elicit ‘blocking antibodies’, and PorB, an outer membrane porin which contributes to immunosuppression. As meningococcal PorB has adjuvant properties, we replaced gonococcal PorB with a meningococcal PorB. Immunisation with OMVs from N. gonorrhoeae lacking rmpM and expressing meningococcal porB elicited higher antibody titres against model antigens in mice compared to OMVs with native PorB. Further, a gonococcal protein microarray revealed stronger IgG antibody responses to a more diverse range of antigens in the Nm PorB OMV immunised group. Finally, meningococcal PorB OMVs resulted in a Th1-skewed response, exemplified by increased serum IgG2a antibody responses and increased IFNɣ production by splenocytes from immunised mice. In summary, we demonstrate that the replacement of PorB in gonococcal OMVs enhances immune responses and offers a strategy for gonococcal vaccine development. |
| first_indexed | 2024-12-09T03:25:00Z |
| format | Journal article |
| id | oxford-uuid:f4579f02-aca4-4d38-8d36-2fc852612fed |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:25:00Z |
| publishDate | 2024 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:f4579f02-aca4-4d38-8d36-2fc852612fed2024-11-26T20:16:30ZTackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine designJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f4579f02-aca4-4d38-8d36-2fc852612fedEnglishJisc Publications RouterPublic Library of Science2024Jones, RARamirez-Bencomo, FWhiting, GFang, MLavender, HKurzyp, KThistlethwaite, AStejskal, LRashmi, SJerse, AECehovin, ADerrick, JPTang, CMGonorrhoea, caused by Neisseria gonorrhoeae, is a common sexually transmitted infection. Increasing multi-drug resistance and the impact of asymptomatic infections on sexual and reproductive health underline the need for an effective gonococcal vaccine. Outer membrane vesicles (OMVs) from Neisseria meningitidis induce modest cross-protection against gonococcal infection. However, the presence of proteins in OMVs derived from N. gonorrhoeae that manipulate immune responses could hamper their success as a vaccine. Here we modified two key immunomodulatory proteins of the gonococcus; RmpM, which can elicit ‘blocking antibodies’, and PorB, an outer membrane porin which contributes to immunosuppression. As meningococcal PorB has adjuvant properties, we replaced gonococcal PorB with a meningococcal PorB. Immunisation with OMVs from N. gonorrhoeae lacking rmpM and expressing meningococcal porB elicited higher antibody titres against model antigens in mice compared to OMVs with native PorB. Further, a gonococcal protein microarray revealed stronger IgG antibody responses to a more diverse range of antigens in the Nm PorB OMV immunised group. Finally, meningococcal PorB OMVs resulted in a Th1-skewed response, exemplified by increased serum IgG2a antibody responses and increased IFNɣ production by splenocytes from immunised mice. In summary, we demonstrate that the replacement of PorB in gonococcal OMVs enhances immune responses and offers a strategy for gonococcal vaccine development. |
| spellingShingle | Jones, RA Ramirez-Bencomo, F Whiting, G Fang, M Lavender, H Kurzyp, K Thistlethwaite, A Stejskal, L Rashmi, S Jerse, AE Cehovin, A Derrick, JP Tang, CM Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design |
| title | Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design |
| title_full | Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design |
| title_fullStr | Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design |
| title_full_unstemmed | Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design |
| title_short | Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design |
| title_sort | tackling immunosuppression by neisseria gonorrhoeae to facilitate vaccine design |
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