<i>Salmonella</i> Typhi Vi capsule prime-boost vaccination induces convergent and functional antibody responses.

dc.contributor.author

Dahora, Lindsay C

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Verheul, Marije K

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Williams, Katherine L

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Jin, Celina

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Stockdale, Lisa

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Cavet, Guy

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Giladi, Eldar

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Hill, Jennifer

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Kim, Dongkyoon

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Leung, Yvonne

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Bobay, Benjamin G

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Spicer, Leonard D

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Sawant, Sheetal

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Rijpkema, Sjoerd

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Dennison, S Moses

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Alam, S Munir

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Pollard, Andrew J

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Tomaras, Georgia D

dc.date.accessioned

2023-09-01T13:28:12Z

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2023-09-01T13:28:12Z

dc.date.issued

2021-10

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2023-09-01T13:28:11Z

dc.description.abstract

Vaccine development to prevent Salmonella Typhi infections has accelerated over the past decade, resulting in licensure of new vaccines, which use the Vi polysaccharide (Vi PS) of the bacterium conjugated to an unrelated carrier protein as the active component. Antibodies elicited by these vaccines are important for mediating protection against typhoid fever. However, the characteristics of protective and functional Vi antibodies are unknown. In this study, we investigated the human antibody repertoire, avidity maturation, epitope specificity, and function after immunization with a single dose of Vi-tetanus toxoid conjugate vaccine (Vi-TT) and after a booster with plain Vi PS (Vi-PS). The Vi-TT prime induced an IgG1-dominant response, whereas the Vi-TT prime followed by the Vi-PS boost induced IgG1 and IgG2 antibody production. B cells from recipients who received both prime and boost showed evidence of convergence, with shared V gene usage and CDR3 characteristics. The detected Vi antibodies showed heterogeneous avidity ranging from 10 μM to 500 pM, with no evidence of affinity maturation after the boost. Vi-specific antibodies mediated Fc effector functions, which correlated with antibody dissociation kinetics but not with association kinetics. We identified antibodies induced by prime and boost vaccines that recognized subdominant epitopes, indicated by binding to the de–O-acetylated Vi backbone. These antibodies also mediated Fc-dependent functions, such as complement deposition and monocyte phagocytosis. Defining strategies on how to broaden epitope targeting for S. Typhi Vi and enriching for antibody Fc functions that protect against typhoid fever will advance the design of high-efficacy Vi vaccines for protection across diverse populations.

dc.identifier.issn

2470-9468

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2470-9468

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https://hdl.handle.net/10161/28889

dc.language

eng

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American Association for the Advancement of Science (AAAS)

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Science immunology

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10.1126/sciimmunol.abj1181

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Humans

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Salmonella typhi

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Typhoid Fever

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Bacterial Vaccines

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Vaccination

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Antibody Formation

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Adult

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Female

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Male

dc.title

Salmonella Typhi Vi capsule prime-boost vaccination induces convergent and functional antibody responses.

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Journal article

duke.contributor.orcid

Bobay, Benjamin G|0000-0003-4775-3686

duke.contributor.orcid

Spicer, Leonard D|0000-0001-5655-0093|0000-0003-2911-6130

duke.contributor.orcid

Alam, S Munir|0000-0003-0941-0703

duke.contributor.orcid

Tomaras, Georgia D|0000-0001-8076-1931

pubs.begin-page

eabj1181

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64

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Duke

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School of Medicine

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Integrative Immunobiology

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Molecular Genetics and Microbiology

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Medicine

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Pathology

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Radiology

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Surgery

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Medicine, Duke Human Vaccine Institute

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Surgery, Surgical Sciences

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Duke Human Vaccine Institute

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Global Health Institute

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Initiatives

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Duke Innovation & Entrepreneurship

pubs.publication-status

Published

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6

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