meningitidis, and have been used to assess and license new meningococcal vaccines [16]. the CHIM setting. Keywords:Vi vaccination, SBA, luminescence, enteric fever, conjugate vaccine, correlates of protection == 1. Introduction == Typhoid fever is a febrile illness caused by infection with the Gram-negative bacteriaSalmonellaenterica serovar Typhi. It is estimated to cause 14.3 million cases per year, leading to approximately 136,000 UNG2 deaths [1,2,3]. Typhoid fever primarily affects low and lower-middle income countries and the major burden of disease lies in Asia and sub-Saharan Africa, where school age children are disproportionately affected [4]. Long term strategies to control enteric fever involve improvements in sanitation, infrastructure, and education, which can be costly and slow [5]. Effective vaccination 2-Deoxy-D-glucose programmes are important in helping to limit disease in the medium term until improvements in water quality are implemented, and are even more important given the emergence of antimicrobial resistant strains and outbreaks [6]. Until 2018 there were two vaccines licensed in many countries available for typhoid fever; the Vi capsular polysaccharide parenteral subunit vaccine, Vi-PS; and Ty21a, a live attenuated oral vaccine (Vivotif, Crucell Vaccines, Leiden, The Netherlands) [7]. These vaccines are not suitable for use in children under 2 or 6 years respectively, they offer only moderate efficacy and do not confer long term protection [8,9]. Protection following inoculation with purified Vi polysaccharide, a T cell-independent antigen, illustrates the key importance of Vi-specific humoral immunity for the control of typhoid fever. Recently a new conjugate typhoid vaccine has been developed which links Vi polysaccharide to a carrier protein to stimulate T cell help, driving immunological memory. The 2-Deoxy-D-glucose Vi tetanus toxoid conjugate vaccine (Vi-TT, Typbar-TCV, Bharat Biotech, Hyderabad, India) has been shown to be safe and efficacious in both adults and children [10,11,12]. The efficacy of the Vi-TT vaccine was demonstrated to be similar to the Vi-PS vaccine in healthy adults in a controlled human infection model (CHIM) [10]. Early results from a Phase III trial in Nepal demonstrate a protective efficacy of 81.6% after one year in children between 9 months and 16 years [11]. Therefore, Vi-TT vaccine and other Vi conjugates are promising candidates for the future control of typhoid fever, even in young children. Currently, there is no accepted correlate of protection associated with either natural exposure, or vaccine induced protection for typhoid fever. Defining a correlate of protection could allow licensure of next generation vaccines without costly large scale efficacy trials, and would provide insight into the mechanism of action of these vaccines [13]. Knowledge of the mechanisms driving protection fromS.Typhi infection may also contribute to the understanding 2-Deoxy-D-glucose of immunity to other typhoidalSalmonellaserovars such asSalmonellaParatyphi A, the second leading cause of enteric fever, for which there is currently no licensed vaccine [3]. We have previously shown in a CHIM study where participants were allocated to receive Vi-TT, Vi-PS or a control vaccine (MenACWY) prior to oral challenge with 15 104colony forming units (CFU)SalmonellaTyphi (Quailes strain), individuals with higher anti-Vi IgG titres at the time of exposure were less likely to develop acute typhoid fever, yet IgG antibody titre alone was a relatively poor indicator of protection [10]. Vi IgA quantity and fold change after vaccination were strongly associated with outcome of challenge [14]. The capacity of Vi-specific antibodies to induce certain effector functions may.