Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections
Recurrent urinary tract infections (rUTI) are a serious disease associated with morbidities and mortality. Resistance to the standard of care antibiotics is now widespread because of the continued use of antibiotics among people who suffer from rUTI. We are therefore developing a vaccine to prevent...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2020.1770034 |
| _version_ | 1797633741385891840 |
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| author | Courtney M. Starks Michelle M. Miller Peter M. Broglie Joshua Cubbison Steven M. Martin Gary R. Eldridge |
| author_facet | Courtney M. Starks Michelle M. Miller Peter M. Broglie Joshua Cubbison Steven M. Martin Gary R. Eldridge |
| author_sort | Courtney M. Starks |
| collection | DOAJ |
| description | Recurrent urinary tract infections (rUTI) are a serious disease associated with morbidities and mortality. Resistance to the standard of care antibiotics is now widespread because of the continued use of antibiotics among people who suffer from rUTI. We are therefore developing a vaccine to prevent recurrences among patients with rUTI. The antigen of the vaccine is FimH, a bacterial adhesin protein, and the vaccine is adjuvanted with a TLR-4 agonist. In a Phase 1 clinical study evaluating the vaccine, immunized individuals produced FimH-binding antibodies. Here we describe the optimization, qualification, and use of an assay to assess the functionality of these anti-FimH antibodies. The suitability of the assay for its intended purpose was demonstrated by selectivity, specificity, sensitivity, and intra-assay and inter-assay precision. The acceptance criteria were achieved for all parameters including intra-assay precision with ≤10% relative standard deviations and inter-assay precision with ≤25% relative standard deviations. The results presented herein suggest this functional assay will be important for supporting the vaccine’s efficacy in future human studies. Furthermore and of great significance, these results prove that vaccine-induced functional antibodies can be elicited in rUTI patients against an essential virulence factor, FimH. |
| first_indexed | 2024-03-11T11:58:07Z |
| format | Article |
| id | doaj.art-c15ede1b79074204abc5cb76d24ad229 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T11:58:07Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-c15ede1b79074204abc5cb76d24ad2292023-11-08T11:55:19ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2021-01-0117128329210.1080/21645515.2020.17700341770034Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infectionsCourtney M. Starks0Michelle M. Miller1Peter M. Broglie2Joshua Cubbison3Steven M. Martin4Gary R. Eldridge5Sequoia Sciences, Inc., 1912 Innerbelt Business Center DriveBioAgilytix Labs, LLCBioAgilytix Labs, LLCBioAgilytix Labs, LLCSequoia Sciences, Inc., 1912 Innerbelt Business Center DriveSequoia Sciences, Inc., 1912 Innerbelt Business Center DriveRecurrent urinary tract infections (rUTI) are a serious disease associated with morbidities and mortality. Resistance to the standard of care antibiotics is now widespread because of the continued use of antibiotics among people who suffer from rUTI. We are therefore developing a vaccine to prevent recurrences among patients with rUTI. The antigen of the vaccine is FimH, a bacterial adhesin protein, and the vaccine is adjuvanted with a TLR-4 agonist. In a Phase 1 clinical study evaluating the vaccine, immunized individuals produced FimH-binding antibodies. Here we describe the optimization, qualification, and use of an assay to assess the functionality of these anti-FimH antibodies. The suitability of the assay for its intended purpose was demonstrated by selectivity, specificity, sensitivity, and intra-assay and inter-assay precision. The acceptance criteria were achieved for all parameters including intra-assay precision with ≤10% relative standard deviations and inter-assay precision with ≤25% relative standard deviations. The results presented herein suggest this functional assay will be important for supporting the vaccine’s efficacy in future human studies. Furthermore and of great significance, these results prove that vaccine-induced functional antibodies can be elicited in rUTI patients against an essential virulence factor, FimH.http://dx.doi.org/10.1080/21645515.2020.1770034urinary tract infectionvaccinefunctional assayfimhtlr-4 agonist |
| spellingShingle | Courtney M. Starks Michelle M. Miller Peter M. Broglie Joshua Cubbison Steven M. Martin Gary R. Eldridge Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections Human Vaccines & Immunotherapeutics urinary tract infection vaccine functional assay fimh tlr-4 agonist |
| title | Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections |
| title_full | Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections |
| title_fullStr | Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections |
| title_full_unstemmed | Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections |
| title_short | Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections |
| title_sort | optimization and qualification of an assay that demonstrates that a fimh vaccine induces functional antibody responses in women with histories of urinary tract infections |
| topic | urinary tract infection vaccine functional assay fimh tlr-4 agonist |
| url | http://dx.doi.org/10.1080/21645515.2020.1770034 |
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