EAVI

The challenge

Sub-Saharan Africa bears the brunt of neglected tropical diseases (NTDs), yet has access to relatively few vaccines to control them. This reflects both limited research into such vaccines, as well as a lack of clinical trials of candidate vaccines in sub-Saharan Africa, leading to limited data from African populations and delayed licensing decisions.

One example is a recently licensed vaccine, IXCHIQ, which protects against the chikungunya virus. Although chikungunya is a growing public health threat in multiple sub-Saharan African countries, the vaccine is not yet widely available in the region. IXCHIQ is a highly immunogenic vaccine that should offer good protection against the virus. However, as it is a live attenuated vaccine, there are concerns about its use in people living with HIV, of whom there are 25 million in sub-Saharan Africa, particularly those whose infections are not well controlled. It is therefore important to demonstrate its safety in African populations. 

The project

The EAVI project is establishing a new European–African partnership to accelerate the development and deployment of new NTD vaccines in sub-Saharan Africa. IXCHIQ is being used as a pathfinder, with clinical studies generating data on the vaccine in African populations.

The project is organising a phase IIIb trial in Kenya and Tanzania of IXCHIQ’s safety and immunogenicity. The trial is focusing on adults, and participants will include people living with HIV, providing the first data on the vaccine in this group. Socio-behavioural studies will explore the acceptability of the vaccine within communities in these two countries.

The study also incorporates intensive analyses of immune responses in vaccine recipients, including comparisons between HIV-positive and -negative participants. It will assess:

• Seroconversion rates: the proportion of recipients who mount immune responses likely to be protective;
• Cross-reactivity: the ability of blood samples from vaccine recipients to neutralise different strains of chikungunya and related viruses;
• The nature of T-cell and antibody responses following vaccination.

The project team will also explore which structural features of the virus stimulate protective immune responses, to inform future vaccine design. In addition, it will apply state-of-the-art single-cell RNA sequencing technologies to gain deep insights into T-cell and B-cell responses and how they differ between HIV-positive and HIV-negative individuals.

A further focus will be on surveillance and disease prevention, as the chikungunya disease burden is unclear and infections are likely underreported in sub-Saharan Africa. Community exposure to the virus will be assessed by determining how many community members have circulating antibodies to chikungunya, while insect vectors transmitting the virus will be captured and analysed for the presence of the virus. How the virus genome changes over time will be monitored in trial participants to provide insights into viral evolution. This information will provide a clearer picture of the current and future burden of chikungunya to inform national decision-making on the use of the vaccine. 

In addition to these chikungunya-specific studies, the project is carrying out a wide range of activities to lay the groundwork for future NTD vaccine studies in the region. These include developing guidance, master protocols and training materials for future trials, holding discussions with key national stakeholders, and engaging with communities to identify potential barriers to clinical studies.

Impact

The EAVI will generate key data on a newly developed chikungunya vaccine while also laying the ground for future neglected tropical diseases (NTDs) vaccine studies. It will:

• Provide data on the safety and immunogenicity of IXCHIQ in African populations.
• Generate the first data from people living with HIV.
• Collect extensive data on immune responses to the vaccine and how these differ in people living with HIV.
• Establish a framework for the evaluation of other NTD vaccines in the future.

NTDs have a huge impact on the quality of life of people across sub-Saharan Africa, as well as a major economic impact. Creating a framework for NTD vaccine testing in Africa could accelerate vaccine testing, licensing and implementation, reducing the burden of these highly prevalent infections. 

Clinical trial sponsor

KENYA MEDICAL RESEARCH INSTITUTE

Location: Nairobi, Kenya