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

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. 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. 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.