DENSTAR

The challenge

Dengue is a debilitating viral disease causing a range of symptoms, including fever, muscle and joint pain, and skin rashes. Mild cases can force adults to miss work and children to lose out on schooling, while severe cases can lead to hospitalisation and even death. Spread by mosquitoes, dengue viral infections have become increasingly common in recent decades (1990 to 2021), leading to tens of millions of cases and tens of thousands of deaths globally. In particular, during 2023-2024, the African region faced an increasing risk. Most dengue infections are asymptomatic or cause nonspecific symptoms that can easily be mistaken for other conditions; therefore, reported cases are likely significantly underestimated. It is estimated that around one in four infected people develops noticeable symptoms.

Four ‘serotypes’ of dengue virus are in circulation globally: DENV1–4. Infection with one serotype leads to some protective immunity against other serotypes, but this protection wanes over time and leads to a risk of a severe reaction if someone is subsequently infected with a different serotype. 

There is currently no specific antiviral treatment, and prevention primarily relies on mosquito control. However, this approach is becoming more difficult due to insecticide resistance, rapid urban growth, climate change, and limited community involvement. Existing vaccines provide only partial protection and can only be used in certain situations. This highlights the urgent need for a safe, effective, and widely accessible dengue vaccine, especially in sub-Saharan Africa, where the risk is rising and access to preventive tools is still limited.

The project

The DENSTAR project is advancing a new tetravalent dengue vaccine, DengiAll, that covers all four dengue virus serotypes and generates robust, balanced immune responses, with a low risk of severe reactions following post-vaccination infection. It is also a single-dose vaccine, unlike existing vaccines, which require multiple doses, shows good stability, and is relatively simple to manufacture, suitable for technology transfer and is optimised for mass deployment in public health programmes and vaccination campaigns.

A large phase III trial of DengiAll is underway in India in adults, and a phase I/II safety and immunogenicity study is planned for younger age groups. The DENSTAR project is generating complementary evidence on DengiAll in African adults and children to confirm that the DengiAll vaccine is safe and effective in this population, building on data generated in India. 

First, a phase I safety study will be carried out in Mozambique, with vaccination initially in adults and then progressively in younger groups down to age 2. Around 100 recipients will be followed for six months. 

Assuming no safety issues are identified, a phase III trial will follow as an extension of the first study, in Mozambique and at additional sites in Ghana and the Democratic Republic of the Congo (DRC). This study is designed to assess immune responses to each of the four Dengue virus (DENV) serotypes and compare them with those observed in the Indian trial. Protective efficacy will therefore be inferred rather than measured directly, which allows for a simpler and shorter trial.

A secondary set of activities focuses on introducing a dengue human challenge model in Gabon.  This will involve volunteers being directly infected with an attenuated challenge strain of DENV under carefully monitored conditions to determine the effectiveness of prior vaccination.  These activities will focus on a naturally occurring attenuated strain of DENV4 isolated in Puerto Rico, where it caused asymptomatic infections. This study will close an important knowledge gap, as existing clinical trial data do not cover protection against DENV4 (which was not circulating when the trials were conducted).

The DENV4 model and challenge will first be developed by collaborators in the US before being transferred to a site in Gabon. Around 30 adult volunteers will be vaccinated with DengiAll and then challenged with DENV4 six months later. 

The project will consult with national regulators on the evidence needed for licensing. When results are available, it will begin the registration process for DengiAll in the DRC, Ghana and Mozambique.

Impact

The DENSTAR project could have a major impact on dengue control in sub-Saharan Africa. It will:

• Generate data on the safety and immunogenicity of DengiAll in African populations, from which vaccine efficacy can be inferred.
• Advance a vaccine that would be relatively straightforward to manufacture in Africa, which the current manufacturer is willing to facilitate.
• Provide a full data package that should be sufficient to support registration in pathfinder African countries. 

A safe and effective vaccine against dengue could help to reduce the growing health and economic burden of dengue fever in sub-Saharan Africa, which is otherwise predicted to grow markedly due to climate change.