Safety and immunogenicity of Vi-typhoid conjugate vaccine co-administration with routine 9-month vaccination in Burkina Faso: A randomized controlled phase 2 trial

Abstract

In 2017, the World Health Organisation (WHO) pre-qualified a single-dose typhoid conjugate vaccine (TCV) and identified TCV co-administration studies as a research priority. Accordingly, we tested co-administration of Typbar TCV 1 (Bharat Biotech International) with measles-rubella (MR) and yellow fever (YF) vaccines. Methods: We conducted a randomized, double-blind, and controlled, phase 2 trial in Ouagadougou, Burkina Faso. Healthy children aged 9-11 months were randomized 1:1 to receive TCV (Group 1) or control vaccine (inactivated polio vaccine (IPV), Group 2). Vaccines were administered intramuscularly with routine MR and YF vaccines. Safety was assessed by (1) local and systemic reactions on days 0, 3, and 7; (2) unsolicited adverse events within 28 days; and (3) serious adverse events (SAEs) within six months after immunization. Results: We enrolled, randomized, and vaccinated 100 eligible children (49 Group 1 and 51 Group 2). Safety outcomes occurred with similar frequency in both groups: local/solicited reactions (Group 1: 1/49, Group 2: 3/50), systemic/solicited reactions (Group 1: 4/49, Group 2: 9/50), unsolicited adverse events (Group 1: 26/49, Group 2: 33/51), and SAEs (Group 1: 2/49, Group 2: 3/51). TCV conferred robust immunogenicity without interference with MR or YF vaccines. Conclusion: TCV can be safely co-administered with MR and YF vaccines to children at the 9-month vaccination visit.

Safety and immunogenicity of a typhoid conjugate vaccine among children aged 9 months to 12 years in Malawi: a nested substudy of a double-blind, randomised controlled trial

“…More recently, Typbar TCV was shown to be immunogenic in Burkinabe infants aged 9–11 months (88%) 28 days after vaccination. 26 A similar TCV, produced by another manufacturer, which is also conjugated to tetanus toxoid and licensed for use in India, showed a 100% seroconversion in Indian children from 6 months to 12 years of age 42 days after vaccination, and an 84% seroconversion rate 12 months after vaccination. 27 In the five aforementioned trials, 14 , 24 , 25 , 26 , 27 TCVs were well tolerated with mild reactogenicity, most commonly fever and pain at injection site.…”

Controlled Human Infection Models To Accelerate Vaccine Development

“…A Phase 3 study of over 28,000 children in Malawi compared TCV against meningococcus A vaccine and found an overall efficacy of 81 percent (444). Two Phase 2 studies in Burkina Faso confirmed the safety of TCV and its compatibility with other routine immunizations (445,446). These results suggest TCV can play a crucial role in mitigating the impact of S. Typhi, including antimicrobial-resistant infections.…”

Typhoid Conjugate Vaccines: Advancing the Research and Public Health Agendas

“…Results from Burkina Faso on coadministration of TCV with yellow fever and measles-rubella vaccines at 9 months of age and group A meningococcal conjugate vaccine at 15 months old showed comparable TCV antibody responses in the countries where efficacy has been demonstrated ( Table 2 ), again confirming the consistency in the performance of this vaccine across diverse settings. For all vaccines tested—yellow fever, measles-rubella, and group A meningococcal conjugate—antibody responses were similar in the groups receiving concomitant TCV as compared to the groups not receiving concomitant TCV [ 23 , 24 ]. This demonstrates safe coadministration is possible, which facilitates incorporation into routine immunization schedules.…”