A Salmonella Typhi Controlled Human Infection Study for Assessing Correlation between Bactericidal Antibodies and Protection against Infection Induced by Typhoid Vaccination

Jones, Elizabeth; Jin, Chunlin; Stockdale, Lisa; Dold, Christina; Pollard, Andrew J.; Hill, Jennifer

doi:10.3390/microorganisms9071394

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…Serum bactericidal antibody (SBA) levels were shown to poorly correlate with disease and anti-Vi IgG and IgM titers. 26 Similarly, no significant correlation was observed between the fold change in anti-Vi IgG and IgA and typhoid fever. 27 Third, the immune equivalence of the two formulations was evaluated only in the adult age group.…”

Section: Discussionmentioning

confidence: 97%

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age

Carlos

Tadesse

Borja-Tabora

et al. 2022

The Lancet Regional Health - Western Pacific

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Section: Discussionmentioning

confidence: 97%

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age

Carlos

Tadesse

Borja-Tabora

et al. 2022

The Lancet Regional Health - Western Pacific

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“…In the controlled human infection model (CHIM) studies, serum IgG and SBA titers at the time of challenge after vaccination with Vi-PS or Vi-TT poorly matched with the protection against S . Typhi 46 . Instead, serum IgA titers showed significant correlation with Vi-PS-induced protection 47 , underscoring potential role for intestinal sIgA.…”

Section: Discussionmentioning

confidence: 99%

Intranasal immunization of mice with chimera of Salmonella Typhi protein elicits protective intestinal immunity

Chakraborty,

Dutta,

Pal

et al. 2024

npj Vaccines

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Development of safe, highly effective and affordable enteric fever vaccines is a global health priority. Live, oral typhoid vaccines induce strong mucosal immunity and long-term protection, but safety remains a concern. In contrast, efficacy wears off rapidly for injectable, polysaccharide-based vaccines, which elicit poor mucosal response. We previously reported Salmonella Typhi outer membrane protein, T2544 as a potential candidate for bivalent (S. Typhi and S. Paratyphi A) vaccine development. Here, we show that intranasal immunization with a subunit vaccine (chimera of T2544 and cholera toxin B subunit) induced strong systemic and intestinal mucosal immunity and protection from S. Typhi challenge in a mouse model. CTB-T2544 augmented gut-homing receptor expression on lymphocytes that produced Th1 and Th17 cytokines, secretory IgA in stool that inhibited bacterial motility and epithelial attachment, antibody recall response and affinity maturation with increased number of follicular helper T cells and CD4+ central and effector memory cells.

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“…High-avidity antibodies with antibody Fc effector functions correspond with protection from disease in a typhoid CHIM ( 16 , 17 ). Serum bactericidal activity did not correlate with protection; however, the role of complement activation as part of a polyfunctional response is not fully understood ( 49 ). There is room to improve on the efficacy of the Vi-TT vaccine regimen to move from 82 and 85% efficacy in Nepal and Bangladesh, respectively ( 13 , 50 ), to an ideal of 100% in diverse populations, including immunocompromised individuals.…”

Section: Discussionmentioning

confidence: 99%

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

Dahora

Verheul

Williams³

et al. 2021

Sci. Immunol.

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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 immunizations 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, while 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 10µM-500pM, 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 Salmonella 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.

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A Salmonella Typhi Controlled Human Infection Study for Assessing Correlation between Bactericidal Antibodies and Protection against Infection Induced by Typhoid Vaccination

Cited by 10 publications

References 32 publications

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age

Intranasal immunization of mice with chimera of Salmonella Typhi protein elicits protective intestinal immunity

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

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