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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - ZIKAVAX (Fast track development of a Zika vaccine based on measles vector)

Teaser

Summary

Zika virus infection is a vector borne disease which has called the attention of the international community due to a large outbreak in 2015. As of July 2019, the World Health Organization (WHO) reported a total of 87 countries with evidence of mosquito-borne transmission of Zika virus, supported by the recent studies which have provided new information on the incidence, prevalence, and patterns of Zika virus transmission worldwide.
There is no specific treatment or vaccine available against Zika virus. Preventive measures are centred on avoiding mosquito bites, reducing other forms of transmission (e.g. sexual transmission) and controlling the vector (mosquitos). These measures can, however, be challenging and have variable efficacy. Although disease symptoms are generally mild, the possible complications to pregnancy, new-borns and neurologic complications in adults, highlight the need of effective measures to prevent this disease. In this context, in March 2016, experts gathered at WHO agreed that the development of a preventive vaccine is a major priority to respond to Zika epidemics in the future. A Zika vaccine development technology roadmap was released by WHO that aims at providing a strategic framework for both outbreak and endemic use for vaccine researchers, funders and product developers.
ZIKAVAX is a collaborative project funded under the European Unionâ€™s Horizon 2020 Research and Innovation Programme (H2020). The four-year project was initiated in October 2016 and has an overall budget of approximately â‚¬ 5 million. The project is the joint effort of leading European experts from academia and industry with unique and specific technological expertise in viral vectors and vaccine development. ZIKAVAX is coordinated by the European Vaccine Initiative (EVI) and includes Institut Pasteur Paris, Themis Bioscience GmbH and the Commissariat Ã l\'Ã©nergie atomique et aux Ã©nergies alternatives.
The ZIKAVAX project aims at developing a safe, effective, and affordable preventive vaccine against Zika virus infection. To achieve this goal, ZIKAVAX uses a delivery platform technology based on a measles vector (MV) with demonstrated proof of principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. The ultimate goal of ZIKAVAX is the demonstration of safety and immunogenicity of a recombinant measles-Zika vaccine candidate (MV-ZIKV) in adult volunteers in a phase Ia clinical trial.
Specific objectives are:
1. To construct and characterise recombinant MV expressing Zika virus proteins as soluble secreted antigens
2. To demonstrate preclinical immunogenicity and protective efficacy of the recombinant MV-ZIKV vaccine candidate(s) in a mouse model and in a non-human primate (NHP) model of Zika virus infection
3. To manufacture a good manufacturing practice (GMP) clinical lot of the MV-ZIKV vaccine candidate using scalable platform technology
4. To assess the safety and immunogenicity of the MV-ZIKV vaccine candidate in a phase I dose-escalation clinical trial

Work performed

Within the first 3 years, ZIKAVAX has assessed a large number of Zika antigens for expression and has down-selected three MV-ZIKV vaccine candidates for testing in the mouse model. Based on the immunogenicity and efficacy results in mice, one of the vaccine candidates (MV-ZIKA RSP) has been selected for evaluation in NHP challenge studies for immunogenicity and efficacy, in comparison to a control vaccine and a first generation MV-ZIKV vaccine. Similar results were obtained in both animal models, providing the rational for further development of MV-ZIKA RSP. The vaccine was GMP manufactured and has entered phase I clinical trial for safety and immunogenicity assessment in Mid-2019. Results of the clinical trial will be available at the end of the project in September 2020.
Overall, the ZIKAVAX project progressed according to the objectives, tasks and timelines as set out in the work plan.

Final results

Although WHO has declared by end of 2016 that Zika virus represents no longer a Public Health Emergency of International Concern, Zika virus and associated neurological consequences remain a significant enduring public health challenge that requires intense action. Therefore, the development of an effective vaccine candidate that is able to prevent the virus spread â€“ also from human to human â€“ and protect humans from neurological disorders would be a very important step forward.
Responding to the spread of the Zika outbreak directly addresses the Sustainable Development Goal (SDG) 3.3 which prioritizes the development, research, and access to medicines and vaccines. The development of a vaccine against Zika, as proposed in ZIKAVAX, will be an important contribution to achieving the SDG tools and is strongly aligned with calls from the WHO Emergency Committee that highlighted the importance of aggressive measures to control the Zika outbreak. Indeed, Zika is a wake-up call for the way we address health and development in the SDG era.
At present there is no specific treatment or vaccine available against Zika virus disease. Both WHO and experts recently convened by WHO agree that the development of a vaccine is a major priority for responding to Zika epidemics in the future and that fast-track research and development of new products, including vaccines, is urgently required. A number of Zika vaccine candidates are currently under early phase clinical development.
ZIKAVAX fast tracks the development of a Zika vaccine based on one of the safest and most efficacious vaccines available to date -the live attenuated measles vaccine. This delivery platform technology has demonstrated proof of principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens, thereby allowing for an extremely rapid and highly cost-efficient development of vaccines. Cost efficiency is further enhanced by an improved manufacturing process achieved by Themis that would also be highly suitable for technology transfer to low- and middle-income countries, if considered appropriate.
Lack of relevant animal challenge models has been identified as a major bottleneck for the development of Zika vaccines. For selecting the best vaccine candidates to move forward into clinical trials in humans, determining the efficacy of vaccine candidates in relevant and validated animal models relevant for humans is crucial. Testing of vaccine candidates in such challenge models will avoid expensive failures of products in mid to late stage clinical testing. ZIKAVAX has developed a Zika challenge model in NHPs, a species highly relevant for the selection of vaccine candidates for Zika. The challenge model developed by the consortium will be made available to other researchers from public and private sector, thereby addressing a major obstacle for the development of product against Zika and increasing the chances of developing effective vaccines as cost-efficient as possible.
Upon demonstration of safety and immunogenicity of the MV-ZIKA RSP vaccine candidate in phase I clinical trial, further clinical development is envisaged by Themis and partners beyond the ZIKAVAX project.