A multi-centre, single arm, Phase 3 study to assess the safety and reactogenicity of biological Es Vi-capsular polysaccharide-CRM197 conjugate typhoid vaccine in ≥6 months old infants to ≤45 years old adults.

Typhoid fever is a serious bacterial infection caused by Salmonella Typhi , with a significant burden in low- and middle-income countries, particularly in Sub-Saharan Africa and South/Southeast Asia. To mitigate its spread, the World Health Organization (WHO) advocates for typhoid vaccination programs targeting high-risk populations. However, unconjugated polysaccharide vaccines have shown limited efficacy in children under two years of age. Biological E has developed a typhoid conjugate vaccine, TYPHIBEV®, which incorporates the Vi-polysaccharide conjugated to the CRM 197 carrier protein. TYPHIBEV®’s safety and immunogenicity were evaluated in Phase 1 and Phase 2/3 clinical trials involving infants, children, adolescents, and adults, compared to an established licensed vaccine. This Phase 3 study was specifically designed to assess the safety profile of TYPHIBEV® in the target population aged ≥6 months to ≤45 years. A multi-centre, single-arm, non-comparative Phase 3 study was conducted to evaluate the safety, tolerability and reactogenicity of a single intramuscular dose of Biological E's Vi-capsular Polysaccharide-CRM 197 Conjugate Typhoid Vaccine. A total of 1770 subjects were enrolled into three age subsets; infants and toddlers, ≥6 months to <2 years of age; children and adolescents, ≥2 years to <18 years of age; and adults, ≥18 years to ≤45 years of age ( n = 590 in each age group). A single dose of THPHIBEV® was administered, and all the subjects were followed up for a period of 42 days. Solicited local and systemic AEs were recorded up until 7 days post-vaccination and unsolicited AEs, serious AEs (SAEs) and medically attended AEs (MAAEs) were recorded throughout the study duration. A total of 114 AEs were recorded in 101 (5.71 %) participants. A majority of these AEs were solicited in nature with general disorders and administration site conditions reported in 5.42 % of participants. The most commonly reported AEs were injection site pain and pyrexia. All MAAEs (1.30 % subjects) were solicited and pyrexia (0.85 % of subjects) was the most common reason for medical attention. No severe or serious AEs and/or deaths were reported throughout the study. None of the subjects discontinued the study due to an AE. TYPHIBEV® was found to be safe and well tolerated across different age groups and the safety profile was comparable to other TCVs in terms of reported solicited and unsolicited AEs. No severe or serious AEs were reported during the entire study period.