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Review
. 2025 Dec;24(1):194-205.
doi: 10.1080/14760584.2025.2476525. Epub 2025 Mar 11.

Typhoid conjugate vaccines: is a single dose enough for durable protection?

Vipin M Vashishtha  1 , Puneet Kumar  2
Affiliations
Free article
Review

Typhoid conjugate vaccines: is a single dose enough for durable protection?

Vipin M Vashishtha et al. Expert Rev Vaccines. 2025 Dec.
Free article

Abstract

Introduction: Typhoid fever is widespread in developing countries. Most typhoid vaccines have gone into some disrepute for their substantial side effects and low efficacy. The latest typhoid vaccines use Salmonella's Vi-capsular polysaccharide (Vi-CPS) conjugated to a protein carrier. The WHO recommends a single typhoid conjugate vaccine (TCV) dose at six months in endemic countries. However, this schedule is contested.

Areas covered: The molecular structure of Vi-CPS, emerging Vi capsule variants, the impact of de-O acetylation on vaccine immunogenicity, the key features of an effective Vi-PS conjugate vaccine, the immunological correlates of protection, the impact of boosting by a TCV on Vi-antibodies, and knowledge gaps were examined. We have also reviewed TCV efficacy and durability data. Our analysis shows that the vaccines are effective, although immunity wanes after five years, especially in children under two. We also offered ways to improve TCV efficacy and briefly discussed new typhoid vaccine development.

Expert opinion: We believe the TCV schedule necessitates revision. Extending the primary immunization age or incorporating a booster upon school enrollment are reasonable alternatives. Region-specific or universal modifications require further deliberation.

Keywords: Salmonella Typhi; Typhoid fever; Vi-capsular polysaccharide; durability of protection; typhoid conjugate vaccines (TCV); waning.

Plain language summary

Typhoid fever causes significant morbidity and mortality in the developing world, with peak incidence among school-aged children (5–15 years). Many vaccines have been developed to control it, but most are imperfect due to unacceptable adverse effects or limited efficacy. ’Typhoid Conjugate Vaccines“ (TCVs) are the latest vaccines against typhoid fever, created through a process known as ”conjugation,“ which involves attaching the antigen from the bacterium’s wall to a ”carrier’ protein to enhance vaccine efficacy. Experts anticipate that these vaccines will show greater efficacy than their predecessors and require fewer doses. They recommend that a single dose offers long-term protection. However, not all experts agree on this single-dose schedule and continue to emphasize the need to revise this approach. We present our perspective after reviewing the literature on this issue. The review indicates that TCVs have good efficacy, but their effectiveness declines after a few years, particularly when administered to children under two in regions with high disease transmission. This implies that the current WHO recommendation of a single dose for six-month-old babies requires revision. Options that warrant careful consideration include adding a booster dose at school age or raising the age for administering the primary dose. Whether this recommendation should be region-specific or universal is another important aspect to consider carefully.

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