VAC071: A study to assess efficacy of the ChAd63/MVA PvDBP vaccines
Research type
Research Study
Full title
A Phase IIa challenge study to assess efficacy of the Plasmodium vivax malaria vaccine candidates ChAd63 PvDBP and MVA PvDBP in healthy adults living in the UK
IRAS ID
261730
Contact name
Angela Minassian
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Eudract number
2019-000643-27
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 10 months, 31 days
Research summary
Research Summary
Vivax malaria is a major global health problem. There is a great need for a safe and effecive vaccine to prevent vivax malaria infection, but currently, no approved vaccine is available. In this study, we aim to assess whether the new vivax malaria vaccines ChAd63 PvDBP and MVA PvDBP can protect against malaria infection in a malaria challenge study. We will do this by giving participants two vaccinations, one dose of each vaccine, administered 8 weeks apart. Approximately 4 weeks after the second vacccination, we will challenge (deliberately infect) volunteers with malaria. We will do this by injecting a small amount of vivax malaria-infected blood. Following malaria challenge, we will monitor volunteers closely to see if they develop symptoms of malaria and take regular blood samples to monitor the growth of the parasite. By comparing with volunteers who have not received the vaccine (recruited as part of another study), we will be able to assess if the vaccine has worked to protect against malaria. In addition, we will do regular blood tests to assess the immune response and collect information about any symptoms that occur after vaccination. In order to take part in the this study volunteers must be: a healthy adult aged between 18 and 45 years; be able an willing (in the Investigator's opinion) to comply with all study requirements; allow the Investigators to discuss their medical history with their GP; practice continuous effective contraception for the duration of the study (women only); refrain from blood donation. Study participants will be involved in this trial for approximately 1 year.
Summary of Results
Dear VAC071 volunteer, We are writing to update you with the results of the VAC071 malaria vaccine study that you took part in, to summarise the results and to thank you for your invaluable contribution in making this study possible. The initial findings from the study are reported in a pre-print article (preliminary report that has not been peer reviewed) which is available here:
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVDknLRlk3r9Y0tfvaGiBUDbwiDpf99N0bvwWSj9y-2FJifxzDkLJqZcksb1Hp7QvT9ybugtud-2B5Hg-2FAUBOqqsEus-3DdsLT_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKeJ8aL7AxN3PUrlPpLaCCGmfnN1vaGLwLIqW5yZnz8gitHJdZ79WF7dlKRcH53Fc4TC7fyo2gE-2BjmKZu3A1nEL4TBhdgFjNmddIoO-2FBRcGQqLGoanmgKQxnKLaWJp9jfxLB1NYbOgUHwouGsCuKU6KJ3GwQba9joZCidbhwsrxyQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C972ad07fc0bd424063ce08db02b69540%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638106755428956448%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=PRBUkwma5odJQLC5xFy4OFa3A2tzmdwRGN60tNyqY3A%3D&reserved=0
We have included the abstract (summary) of the report at the end of this letter.
The results have also been presented at international medical and scientific conferences. The results from this trial will help us to develop better vaccines against Plasmodium vivax malaria in the future.What the study involved:
You were one of 16 adults who took part in the VAC071 study to test vaccines against Plasmodium vivax malaria. The vaccines are called ChAd63 PvDBP and MVA PvDBP and are what we call viral-vectored vaccines. These vaccines are made from viruses that have been genetically modified to contain genetic material from the P. vivax malaria parasite for a protein called PvDBP that the parasite uses to infect red blood cells and cause malaria. The two vaccines were given 8 weeks apart and then the effectiveness of the vaccines at preventing malaria was tested by infecting participants with malaria by injection of a small amount of malaria infected blood into the arm (malaria challenge). One group of participants received one vaccination just prior to the the trial going on temporary hold for over a year due to the Covid-19 pandemic. The participants who returned to continue in the study received a second dose of the ChAd63 PvDBP vaccine over a year later, before receiving their MVA PvDBP vaccine and then undergoing malaria infection. Participants who underwent malaria infection were compared to a control group who were not vaccinated and underwent malaria infection under the same conditions.The aims of the study were:
• To see if the ChAd63 PvDBP and MVA PvDBP vaccines could slow or stop the growth of malaria parasites in the blood in a malaria challenge, compared with unvaccinated control volunteers
• To continue to assess the short term side effects and the body’s immune response to the vaccines
• To investigate if and how the body’s immune response relates to any protection from malaria infectionWhat the study found:
• Both the ChAd63 PvDBP and MVA PvDBP vaccines caused mainly expected and short lived side effects and there were no serious unexpected side effects
• The most common side effects were pain at the site of vaccination and feeling tired
• The combination of ChAd63 PvDBP and MVA PvDBP vaccines generated antibody (proteins produced by the immune system) and immune cell responses
• On average across the 8 participants that underwent malaria infection, the vaccines did not slow the growth of malaria parasites in the blood or delay the time to developing malaria symptoms compared to unvaccinated control volunteersWhat this means:
• Although the vaccines induced immune responses, these responses on average were not enough to stop or slow the malaria parasite.
• We are now studying the immune response to the vaccines in more detail to see how we can make better vaccines against vivax malaria in the future .The ChAd63 PvDBP and MVA PvDBP vaccines in their current form will not progress to further trials
Although these are not the results we would have hoped for, it is still an important result as we now know that the ChAd63 PvDBP and MVA PvDBP vaccines tested in this study are not effective against P. vivax malaria challenge in humans. It is important to stop further testing of vaccines that are shown to be ineffective in human trials to avoid vaccinating larger number of people who will receive no benefit from it and save money and resources to focus on more effective candidate vaccines. We will now use blood samples taken in this study to try to work out what aspects of the immune response to the vaccines are associated with effectiveness at preventing parasite growth so we can improve the design of similar vaccines that are in development.
We would like to thank all our participants again for their invaluable contribution towards this study, as without you the study would not be possible. If you have any questions regarding these results, please get in touch by email or phone.REC name
South Central - Oxford A Research Ethics Committee
REC reference
19/SC/0193
Date of REC Opinion
22 May 2019
REC opinion
Further Information Favourable Opinion