Periodic Reporting for period 3 - ZIKAVAX (Fast track development of a Zika vaccine based on measles vector)
Berichtszeitraum: 2019-10-01 bis 2020-12-31
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.
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 mosquito vector. These measures can, however, be challenging and have variable efficacy. Although symptoms are generally mild, the possible complications to pregnancy, newborns and neurologic complications in adults, highlight the need of effective measures to prevent this disease. Experts gathered at WHO in 2016 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 provides a strategic framework for both outbreak and endemic use.
The ZIKAVAX project was the joint effort of leading European experts from academia and industry with unique and specific technological expertise in viral vectors and vaccine development. ZIKAVAX was coordinated by the European Vaccine Initiative (EVI) and includes Institut Pasteur Paris, Themis Bioscience GmbH (now part of MSD) and the Commissariat à l'énergie atomique et aux énergies alternatives (CEA).
The ZIKAVAX project aimed at developing a safe, effective, and affordable preventive vaccine against Zika virus infection. To achieve this goal, ZIKAVAX used 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 was 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:
1. Construct and characterise recombinant MV expressing Zika virus proteins
2. Demonstrate preclinical immunogenicity and protective efficacy of the recombinant MV-ZIKV vaccine candidate(s) in mouse model and non-human primate (NHP) models of Zika virus infection
3. Manufacture a good manufacturing practice (GMP) clinical lot of the MV-ZIKV vaccine candidate using scalable platform technology
4. Assess the safety and immunogenicity of the MV-ZIKV vaccine candidate in a phase I dose-escalation clinical trial
In conclusion, the ZIKAVAX project was progressing according to the objectives and tasks as specified and all activities were successfully completed.
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 mosquito vector. These measures can, however, be challenging and have variable efficacy. Although symptoms are generally mild, the possible complications to pregnancy, newborns and neurologic complications in adults, highlight the need of effective measures to prevent this disease. Experts gathered at WHO in 2016 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 provides a strategic framework for both outbreak and endemic use.
The ZIKAVAX project was the joint effort of leading European experts from academia and industry with unique and specific technological expertise in viral vectors and vaccine development. ZIKAVAX was coordinated by the European Vaccine Initiative (EVI) and includes Institut Pasteur Paris, Themis Bioscience GmbH (now part of MSD) and the Commissariat à l'énergie atomique et aux énergies alternatives (CEA).
The ZIKAVAX project aimed at developing a safe, effective, and affordable preventive vaccine against Zika virus infection. To achieve this goal, ZIKAVAX used 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 was 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:
1. Construct and characterise recombinant MV expressing Zika virus proteins
2. Demonstrate preclinical immunogenicity and protective efficacy of the recombinant MV-ZIKV vaccine candidate(s) in mouse model and non-human primate (NHP) models of Zika virus infection
3. Manufacture a good manufacturing practice (GMP) clinical lot of the MV-ZIKV vaccine candidate using scalable platform technology
4. Assess the safety and immunogenicity of the MV-ZIKV vaccine candidate in a phase I dose-escalation clinical trial
In conclusion, the ZIKAVAX project was progressing according to the objectives and tasks as specified and all activities were successfully completed.
The ZIKAVAX consortium successfully screened many Zika antigens and down-selected three MV-ZIKV vaccine candidates for further immunogenicity and efficacy testing in the mouse model. Based on the results, one of the vaccine candidates (MV-ZIKA RSP) was selected for evaluation in NHP challenge studies for immunogenicity and efficacy, in comparison to a control vaccine and a first generation MV-ZIKV vaccine. A joint manuscript on the results of the pre-clinical studies is currently under development and will be submitted for publication in a peer-review journal. The established ZIKV mouse and NHP challenge models will be used to further evaluate additional ZIKV vaccine candidates, treatment options, or to better decipher the immune responses induced by vaccines or natural viral infections.
Following the promising results in the pre-clinical animal models, the MV-ZIKA-RSP vaccine candidate was transitioned to clinical development. The vaccine was GMP manufactured and assessed in toxicity studies. Stability of the vaccine was demonstrated over 24 months. A first-in-man phase I clinical trial was conducted in Austria to investigate the safety and immunogenicity of MV-ZIKA-RSP, a novel liquid vaccine formulation after one or two vaccinations. MV-ZIKA-RSP is a live attenuated recombinant viral vectored vaccine for prophylaxis of Zika virus infection in healthy adults. The clinical trial data indicates that the MV-ZIKA-RSP vaccine candidate was well tolerated and induced immune responses that are currently further evaluated. The clinical study was registered in the public platforms clinicaltrials.gov (NCT04033068) and EudraCT (EudraCT 2019-000840-93). Detailed data was posted in the EudraCT registry.
The consortium partners will continue to communicate and disseminate the project results at international conferences, workshops, and through institutional websites and social media channels to guarantee visibility of the project outcomes. Themis, as part of MSD, will also continue to evaluate the data gathered during ZIKAVAX and depending on the final data analysis, plans to develop a sustainable development plan to advance the vaccine candidate to late-stage clinical trials in endemic countries. With the focus on tropical and neglected infectious diseases Themis will continue to invest in research and development of high-quality vaccine candidates.
Following the promising results in the pre-clinical animal models, the MV-ZIKA-RSP vaccine candidate was transitioned to clinical development. The vaccine was GMP manufactured and assessed in toxicity studies. Stability of the vaccine was demonstrated over 24 months. A first-in-man phase I clinical trial was conducted in Austria to investigate the safety and immunogenicity of MV-ZIKA-RSP, a novel liquid vaccine formulation after one or two vaccinations. MV-ZIKA-RSP is a live attenuated recombinant viral vectored vaccine for prophylaxis of Zika virus infection in healthy adults. The clinical trial data indicates that the MV-ZIKA-RSP vaccine candidate was well tolerated and induced immune responses that are currently further evaluated. The clinical study was registered in the public platforms clinicaltrials.gov (NCT04033068) and EudraCT (EudraCT 2019-000840-93). Detailed data was posted in the EudraCT registry.
The consortium partners will continue to communicate and disseminate the project results at international conferences, workshops, and through institutional websites and social media channels to guarantee visibility of the project outcomes. Themis, as part of MSD, will also continue to evaluate the data gathered during ZIKAVAX and depending on the final data analysis, plans to develop a sustainable development plan to advance the vaccine candidate to late-stage clinical trials in endemic countries. With the focus on tropical and neglected infectious diseases Themis will continue to invest in research and development of high-quality vaccine candidates.
Although WHO has declared in late 2016 that Zika virus represents no longer a Public Health Emergency of International Concern, Zika virus associated complications remain a significant enduring public health challenge. Therefore, the development of an effective vaccine candidate that can prevent the virus spread and protect humans from neurological disorders would be a very important step forward. At present there is no specific treatment or vaccine available against Zika virus disease and it was agreed that the development of a vaccine is a major priority for responding to Zika epidemics in the future and that research and development of new products, including vaccines, is required.
ZIKAVAX fast tracked 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 Themis’ improved manufacturing process that would also be highly suitable for technology transfer to low- and middle-income countries.
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. 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, 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.
The safety and immunogenicity data of the MV-ZIKA RSP vaccine candidate in the phase I clinical trial was carefully evaluated by Themis. Assuming a positive outcome of the assessment, a vaccine development plan will be prepared to advance the vaccine candidate to further clinical development beyond the ZIKAVAX project.
ZIKAVAX fast tracked 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 Themis’ improved manufacturing process that would also be highly suitable for technology transfer to low- and middle-income countries.
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. 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, 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.
The safety and immunogenicity data of the MV-ZIKA RSP vaccine candidate in the phase I clinical trial was carefully evaluated by Themis. Assuming a positive outcome of the assessment, a vaccine development plan will be prepared to advance the vaccine candidate to further clinical development beyond the ZIKAVAX project.