Typhoid Conjugate Vaccine Protective Against Oral Salmonella Typhi Challenge

The Vi-polysaccharide-protein tetanus toxoid-conjugate vaccine (Vi-conjugate) reduced the rate of typhoid fever in a human model of infection compared with control vaccination and increased the rates of geometric mean titers compared with the unconjugated vaccine (Vi-polysaccharide), according to the results of a study published in The Lancet.¹

In this phase 2b study (ClinicalTrials.gov identifier: NCT02324751), healthy adults with no history of typhoid infection were randomly assigned to receive the Vi-conjugate (n=37), Vi-polysaccharide (n=35), or control meningococcal vaccine (n=31). Approximately 1 month postvaccination, volunteers were challenged with oral Salmonella enterica serovar Typhi and assessed for typhoid infection. Typhoid infection was considered fever of 38°C for ≥12 hours or S Typhi bacteremia.¹

More patients in the control group were diagnosed with typhoid (77%) compared with those in the Vi-conjugate (35%) and Vi-polysaccharide groups (35%), resulting in vaccine efficacies of 54.6% and 52.0%, respectively.¹

In a commentary on the study published in the same issue of The Lancet, Nicholas Feasey, MD, of Liverpool School of Tropical Medicine, and Myron Levine, MD, of the University of Maryland School of Medicine, noted that field efficacy of Vi-conjugate vaccine may actually be higher, suggesting that the criteria for the primary end point of typhoid infection used in this study was “better suited to studying typhoid pathogenesis than assessing the efficacy of typhoid vaccines.”²

Approximately 1 month after vaccination, the rate of seroconversion (100% vs 88.6% for Vi-conjugate vs Vi-polysaccharide, respectively) and the mean geometric anti-Vi titers adjusted for baseline (562.9 EU/mL vs 140.5 EU/mL; P <.001) were higher in the Vi-conjugate group.¹

The study authors concluded that the Vi-conjugate vaccine “has the potential to reduce both the burden of typhoid fever and associated health inequality.”¹ According to Drs Feasey and Levine, phase 3 and 4 trials are planned for late 2017, but the present study results “are timely and engender optimism that an effective new instrument has become available to help to control typhoid in hyperendemic populations.”²

References

1. Jin C, Gibani MM, Moore M, et al. Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial [published online September 28, 2017]. Lancet. doi: 10.1016/S0140-6736(17)32149-9
2. Feasey NA, Levine MM. Typhoid vaccine development with a human challenge model [published online September 28, 2017]. Lancet. doi: 10.1016/S0140-6736(17)32407-8