More than 9 million cases of febrile illnesses and 110 000 deaths are attributed to typhoid fever each year.
South Asia accounts for over 70% of the global burden.
Growing antimicrobial resistance in the region, especially outbreaks of cephalosporin-resistant typhoid in Pakistan, poses a challenge in the treatment of typhoid fever.
Although licensed vaccines are available, their use has been limited to travellers. The parenteral Vi polysaccharide vaccines are poorly immunogenic in young children. The oral Ty21a vaccine is not licensed for children younger than 6 years and is difficult for most children to swallow. Vi-rEPA, a typhoid conjugate vaccine (TCV), showed high efficacy in young children; however, never advanced to market approval.
More recently, a new TCV containing a Vi polysaccharide conjugated to tetanus-toxoid protein carrier (Typbar-TCV) has shown high immunogenicity and the ability to elicit immunological responses in young children.
In principle, TCVs can elicit a longer duration of protection in comparison with polysaccharide vaccines.
The WHO Strategic Advisory Group of Experts, in October, 2017, recommended the use of TCV for the control of endemic and epidemic typhoid fever and in December, 2017, Typbar-TCV was WHO-prequalified.
with the aim of establishing the field efficacy of TCV. TyVAC is a partnership between the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, the Oxford Vaccine Group at the University of Oxford, and PATH, an international non-profit organisation. In 2019, we reported the interim results after 1 year of follow-up from the ongoing trial.
A single dose of TCV had an efficacy of 81·6% (95% CI 58·8–91·8; p<0·001) in the first year after vaccination. Seroconversion defined as a 4-fold increase in anti-Vi IgG titres 28 days post-vaccination was 99% in the TCV group. We now report the final efficacy results after 2 years of follow-up.
Study design and participants
Randomisation and masking
Anti-Vi IgG titres were measured by means of a commercial ELISA kit (VaccZyme, The Binding Site, Birmingham, UK) according to the manufacturer guidelines. Anti-Vi IgA titres were assessed with Vi-coated plates and reagents supplied by The Binding Site by means of a protocol adapted from the commercial VaccZyme assay.