Development of Vi conjugate - a new generation of typhoid vaccine

Area of Science:

• Infectious Diseases
• Vaccinology
• Microbiology

Background:

• Typhoid fever poses a significant global health burden, with millions infected annually.
• Existing typhoid vaccines have limitations, notably lacking efficacy in children under five.
• These deficiencies hinder effective typhoid vaccination program implementation.

Purpose of the Study:

• To develop and evaluate improved typhoid vaccines with enhanced immunogenicity and broader age group protection.
• To assess the efficacy and safety of Vi-rEPA conjugate vaccine in young children.
• To explore the potential of Vi conjugate vaccines for typhoid fever prevention.

Main Methods:

• Conjugation of Vi antigen to carrier proteins like rEPA, tetanus toxoid, and CRM197.
• Immunogenicity studies in adults and children comparing Vi conjugates to Vi alone.
• A double-blind, placebo-controlled, randomized efficacy trial of Vi-rEPA in 2- to 5-year-old children.
• Safety and immunogenicity assessment of Vi-rEPA with routine infant vaccines.

Main Results:

• Vi-rEPA demonstrated higher and longer-lasting anti-Vi IgG responses in adults and children compared to Vi alone.
• Immunity persisted for over 8 years in school-age children and adults.
• Vi-rEPA showed 89% protective efficacy against typhoid fever in 2- to 5-year-old children, lasting at least 4 years.
• Vi-rEPA was safe, immunogenic, and showed no interference when co-administered with routine infant vaccines.
• Various Vi conjugates using different carrier proteins proved significantly more immunogenic than Vi alone.

Conclusions:

• Vi conjugate vaccines, including Vi-rEPA, represent a significant advancement in typhoid prevention.
• These vaccines offer robust protection, particularly in vulnerable young children.
• The development and licensure of Vi conjugate vaccines usher in a new era for typhoid fever control and potential elimination.