Abstract

BackgroundSalmonella enterica serovar Typhi is estimated to cause 9 to 13 million cases of typhoid fever annually. Typhoid conjugate vaccines represent a promising prophylactic measure to prevent disease, but there are few data assessing persistence of immunity. The effect of a Vi polysaccharide booster vaccine in individuals previously vaccinated with the Vi-tetanus toxoid typhoid conjugate vaccine has not been assessed previously.MethodsThirty five healthy adult volunteers received a single dose of the Vi conjugate vaccine (Vi-TT) and 37 received a single dose of Vi polysaccharide vaccine (Vi-PS) prior to oral challenge with live S. Typhi bacteria as part of a randomised controlled, phase 2b study. In addition to data previously published showing persistence of Vi IgG and IgA antibodies for 7 months after Vi vaccination, titres were measured at intervals until 13 months post-vaccination. Ten participants who received Vi-TT (both challenged and unchallenged) were re-vaccinated with Vi-PS at an interval of 19-23 months post-prime. Anti-Vi IgG and IgA titres, and Vi-specific antibody secreting cells and memory B cells were measured at seven days and one month post-boost.FindingsVi IgG and IgA antibody titres remained significantly elevated above baseline levels 13 months after priming with Vi-TT, with a 4-fold rise retained in 90% and 88% of recipients (Vi IgG and IgA, respectively). Anti-Vi IgG and IgA antibody titres were found to persist at higher levels in participants who received a single dose of Vi-TT than in those who received Vi-PS. No significant boost in Vi-antibody titre was observed in response to oral challenge with S. Typhi bacteria, one month after vaccination. Following a Vi-PS booster vaccination in those previously vaccinated with Vi-TT, anti-Vi IgG and IgA titres were significantly elevated, with similar titres observed at one month post-boost compared with one month after primary vaccination. The frequency of Vi-specific IgA antibody secreting cells increased significantly 7 days post-boost compared with pre-boost. No memory B cell response was observed following Vi-PS booster vaccination.InterpretationStrong persistence of anti-Vi IgG and IgA following Vi-TT vaccination suggests that the conjugate vaccine may offer durable protection, supporting its use in endemic settings.

Highlights

  • Despite increasing access to improved water sources globally, typhoid fever continues to be prevalent in low and lower middle income countries (LMIC), with an estimated 9 to 13 million cases and 145,000 to 161,000 deaths annually [1]

  • 90% (26/29) of participants vaccinated with Vi tetanus toxoid conjugate (Vi-TT) and 85% (23/27) of participants vaccinated with Vi-PS retained an IgG titre at least four times that of the PV titre 13 months after vaccination. 88% (23/ 26) of participants vaccinated with Vi-TT and 77% (20/26) of participants vaccinated with Vi-PS retained an IgA titre at least four times that of the PV titre 13 months after vaccination

  • In this study we describe the persistence of the Vi antibody response to plain Vi polysaccharide and Vi tetanus toxoid conjugate vaccines, showing a similar kinetic profile with a significant decline in both Vi IgG and IgA titres between one and 13 months after Vi-TT vaccination

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Summary

Introduction

Despite increasing access to improved water sources globally, typhoid fever continues to be prevalent in low and lower middle income countries (LMIC), with an estimated 9 to 13 million cases and 145,000 to 161,000 deaths annually [1]. Antibiotics reduce the fatality rate of patients with an acute infection to around 1%, they have little impact on disease incidence, and improper use of antibiotics can drive the emergence of antibiotic resistant strains [5, 6]. Salmonella enterica serovar Typhi is estimated to cause 9 to 13 million cases of typhoid fever annually. Typhoid conjugate vaccines represent a promising prophylactic measure to prevent disease, but there are few data assessing persistence of immunity. The effect of a Vi polysaccharide booster vaccine in individuals previously vaccinated with the Vitetanus toxoid typhoid conjugate vaccine has not been assessed previously

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