The Strategic Advisory Group of Experts (SAGE) on Immunization advises WHO on global policies for vaccines. In April, 2016, SAGE issued recommendations on the use of the first licenced dengue vaccine, CYD-TDV. In November, 2017, a retrospective analysis of clinical trial data, stratifying participants according to their dengue serostatus before the first vaccine dose, showed that although in high seroprevalence settings the vaccine provides overall population benefit, there was an excess risk of severe dengue in seronegative vaccinees. SAGE's working group on dengue vaccines met to discuss the new data and mainly considered two vaccination strategies: vaccination of populations with dengue seroprevalence rates above 80% or screening of individuals before vaccination, and vaccinating only seropositive individuals. We report on the deliberations that informed the recommendation of the pre-vaccination screening strategy, in April, 2018. Important research and implementation questions remain for CYD-TDV, including the development of a highly sensitive and specific rapid diagnostic test to determine serostatus, simplified immunisation schedules, and assessment of the need for booster doses.
Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines. Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome. Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.
Dengue has emerged as a significant global health threat. Despite decades of research, only two dengue vaccines—CYD-TDV (Dengvaxia) and TAK-003 (Qdenga)—have been licensed to date, with limited implementation. This paper explores and outlines strategies for integrating dengue vaccines into routine immunization programs, particularly in high-burden regions. TAK-003, a tetravalent live-attenuated vaccine, has demonstrated 61% efficacy against virologically confirmed dengue and 84% efficacy against hospitalizations in endemic settings. However, concerns remain about vaccine-enhanced disease, particularly among seronegative individuals exposed to DENV3 and DENV4. WHO recommends targeted introduction in high-transmission settings without pre-vaccination screening, while ongoing post-introduction studies will further clarify long-term safety and efficacy. Effective vaccine rollout requires a multi-pronged approach, including school-based immunization, integration with adolescent health services, and strong community engagement. Decision-making for vaccine introduction should be guided by National Immunization Technical Advisory Groups (NITAGs), local epidemiological data, and cost-effectiveness assessments. While future vaccines, including mRNA and virus-like particle candidates, are under development, optimizing the use of currently available vaccines is crucial to reducing dengue’s public health impact. Given the continued rise in cases, immediate action—combining vaccination with vector control—is essential to prevent further morbidity and mortality.
Invasive disease caused by non-typhoidal Salmonella serovars (iNTS) occurs with increased risk in the presence of other comorbidities such as malaria, HIV, malnutrition, anaemia and sickle cell disease. While infection with non-typhoidal (NTS) serovars often results in self-limited enterocolitis in high-income settings, in sub-Saharan Africa (SSA) where these risk-comorbidities are common, an invasive (iNTS) disease phenotype is seen, associated with up to 20 % case-fatality ratio, and antimicrobial resistance is both significant and growing. The need to evaluate the potential public health value of vaccines against iNTS disease is increasingly being recognized, and several candidate vaccines are in early development. A better understanding of the global burden and epidemiology of iNTS disease, as well as the potential public health and socio-economic benefits that iNTS vaccines may offer is fundamental to support and justify the investments in vaccine development. In addition, the pathways for licensure, policy recommendations and eventual vaccine prioritization and use in low- and middle-income countries (LMICs) need to be defined. Here, we report on the proceedings of an expert consultation held on 29 November - 1 December 2021 as part of an overall project to develop a Full Value of Vaccines Assessment (FVVA) for iNTS vaccines and in addition to more recent iNTS vaccine developments. Experts at the consultation reviewed the current evidence on iNTS disease and discussed knowledge gaps to be addressed to accelerate vaccine development, licensure and introduction, as well as LMIC perspectives on potential iNTS vaccine use and demand. The learnings from this consultation are critical inputs to inform remaining work under the iNTS FVVA project.