Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses

Sian Jossi, Melissa Arcuri, Areej Alshayea, Ruby Persaud, Edith Marcial Juarez, Elena Palmieri, Roberta Di Benedetto, Marisol Perez-Toledo, Jamie Pillaye, Will Channell, Anna Schager, Rachel Lamerton, Charlie Jones, Margaret Goodall, Takeshi Haneda, Andreas J. Bäumler, Lucy H. Jackson-Jones, Kai Toellner, Calman MacLennan, Ian HendersonFrancesca Micoli, Adam Cunningham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Introduction: Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood.

Methods and Results: Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV.

Discussion: Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.
Original languageEnglish
Article number1139329
Number of pages13
JournalFrontiers in immunology
Volume14
DOIs
Publication statusPublished - 23 Mar 2023

Keywords

  • vaccine
  • antibody
  • capsular polysaccharide
  • conjugate
  • typhoid
  • Vi antigen
  • Immunology

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