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

Abstract

IntroductionVaccination 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 resultsHere, 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.DiscussionTherefore, 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.

Drugs, Vaccines and Druggable Targets of Salmonella Typhi

“…The Vi-PS and TCV can be produced using well-established methodologies to ensure manufacturing consistency. Both unconjugated Vi-PS and TCV induced early IgM and IgG responses and classical extrafollicular responses (Jha & Janoff, 2019;Jossi et al, 2023). However, only mice immunized with TCVs exhibited germinal center responses, as expected.…”

Salmonellosis: An Overview of Epidemiology, Pathogenesis, and Innovative Approaches to Mitigate the Antimicrobial Resistant Infections

“…The administration of a S. Typhi Vi polysaccharide with the tetanus toxoid conjugate vaccine (Tybar) vaccine has shown to have an efficacy of up to 85% in children under the age of 2 years, with a high increase in T-cell-independent IgG production [431]. Similarly, another Vi-polysaccharide based Vi Conjugate (Vi-CRM 197 ) and Vi Conjugate (Vi-rEPA) vaccine has demonstrated up to 90% efficacy in children and a similar increase in IgG production lasting up to 4 years post-vaccination against S. Typhi [432,433]. In addition to this, other forms of vaccines are also available or are currently in development (Table 5).…”