Qdenga vaccination of dengue-experienced diabetic adults in Pakistan: a development programme to enable a future randomised controlled trial

This project collects the clinical, immunological, epidemiological, and operational evidence required to enable a future randomised controlled trial of targeted dengue vaccination in high-risk adults with diabetes in Pakistan. Severe dengue is driven by host vulnerability rather than uniform transmission, with diabetes conferring increased risk of hospitalisation and increased mortality. Although WHO (2024) recommends Qdenga (TAK-003) for individuals with comorbidities, no immunogenicity, safety, or delivery data exist for diabetic populations. Work Package 1 defines vaccine response in dengue-experienced diabetic adults through tetravalent neutralising antibody profiling (PRNT50), glycaemic stability monitoring, and mechanistic immunophenotyping of Tfh-B cell responses. Work Package 2 establishes trial- design parameters, including seroprevalence, severe dengue incidence, recruitment feasibility, and circulating serotype distribution. Work Package 3 delivers a consensus-derived, regulatory-ready protocol through Delphi methodology and stakeholder co-design in alignment with Pakistan's policy on Immunization. This development programme will generate eligibility criteria, endpoint definition, sample size inputs, and operational pathways for a definitive trial. This work aims to shift dengue vaccination from population- wide deployment towards intervention on the most vulnerable people at risk of severe complications. Keywords: dengue virus, diabetes mellitus, Qdenga (TAK-003), targeted vaccination, immunogenicity, seroprevalence, trial development, severe dengue, Pakistan.