Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine

Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, ra...
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Autor*in:	Valentino Conti [verfasserIn] Omar Rossi [verfasserIn] Kristen A. Clarkson [verfasserIn] Francesca Mancini [verfasserIn] Usman N. Nakakana [verfasserIn] Eleanna Sarakinou [verfasserIn] Andrea Callegaro [verfasserIn] Pietro Ferruzzi [verfasserIn] Alessandra Acquaviva [verfasserIn] Ashwani Kumar Arora [verfasserIn] Elisa Marchetti [verfasserIn] Francesca Necchi [verfasserIn] Robert W. Frenck [verfasserIn] Laura B. Martin [verfasserIn] Robert W. Kaminski [verfasserIn] Audino Podda [verfasserIn] Francesca Micoli [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Übergeordnetes Werk:	In: npj Vaccines - Nature Portfolio, 2017, 9(2024), 1, Seite 10
Übergeordnetes Werk:	volume:9 ; year:2024 ; number:1 ; pages:10

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41541-024-00822-2

Katalog-ID:	DOAJ095582495

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spelling	10.1038/s41541-024-00822-2 doi (DE-627)DOAJ095582495 (DE-599)DOAJ6ec51974ce3d4b6f991542f381a95d13 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Valentino Conti verfasserin aut Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Omar Rossi verfasserin aut Kristen A. Clarkson verfasserin aut Francesca Mancini verfasserin aut Usman N. Nakakana verfasserin aut Eleanna Sarakinou verfasserin aut Andrea Callegaro verfasserin aut Pietro Ferruzzi verfasserin aut Alessandra Acquaviva verfasserin aut Ashwani Kumar Arora verfasserin aut Elisa Marchetti verfasserin aut Francesca Necchi verfasserin aut Robert W. Frenck verfasserin aut Laura B. Martin verfasserin aut Robert W. Kaminski verfasserin aut Audino Podda verfasserin aut Francesca Micoli verfasserin aut In npj Vaccines Nature Portfolio, 2017 9(2024), 1, Seite 10 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:9 year:2024 number:1 pages:10 https://doi.org/10.1038/s41541-024-00822-2 kostenfrei https://doaj.org/article/6ec51974ce3d4b6f991542f381a95d13 kostenfrei https://doi.org/10.1038/s41541-024-00822-2 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2024 1 10
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allfieldsSound	10.1038/s41541-024-00822-2 doi (DE-627)DOAJ095582495 (DE-599)DOAJ6ec51974ce3d4b6f991542f381a95d13 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Valentino Conti verfasserin aut Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Omar Rossi verfasserin aut Kristen A. Clarkson verfasserin aut Francesca Mancini verfasserin aut Usman N. Nakakana verfasserin aut Eleanna Sarakinou verfasserin aut Andrea Callegaro verfasserin aut Pietro Ferruzzi verfasserin aut Alessandra Acquaviva verfasserin aut Ashwani Kumar Arora verfasserin aut Elisa Marchetti verfasserin aut Francesca Necchi verfasserin aut Robert W. Frenck verfasserin aut Laura B. Martin verfasserin aut Robert W. Kaminski verfasserin aut Audino Podda verfasserin aut Francesca Micoli verfasserin aut In npj Vaccines Nature Portfolio, 2017 9(2024), 1, Seite 10 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:9 year:2024 number:1 pages:10 https://doi.org/10.1038/s41541-024-00822-2 kostenfrei https://doaj.org/article/6ec51974ce3d4b6f991542f381a95d13 kostenfrei https://doi.org/10.1038/s41541-024-00822-2 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2024 1 10
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author	Valentino Conti
spellingShingle	Valentino Conti misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine
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topic_title	RC581-607 RC254-282 Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine
topic	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine
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title_full	Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine
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title_sort	putative correlates of protection against shigellosis assessing immunomarkers across responses to s. sonnei investigational vaccine
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title_auth	Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine
abstract	Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.
abstractGer	Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.
abstract_unstemmed	Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.
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title_short	Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine
url	https://doi.org/10.1038/s41541-024-00822-2 https://doaj.org/article/6ec51974ce3d4b6f991542f381a95d13 https://doaj.org/toc/2059-0105
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author2	Omar Rossi Kristen A. Clarkson Francesca Mancini Usman N. Nakakana Eleanna Sarakinou Andrea Callegaro Pietro Ferruzzi Alessandra Acquaviva Ashwani Kumar Arora Elisa Marchetti Francesca Necchi Robert W. Frenck Laura B. Martin Robert W. Kaminski Audino Podda Francesca Micoli
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Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine

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