VAC079: Safety and efficacy of the PvDBPII in Matrix M1 vaccine
Research type
Research Study
Full title
A Phase I/IIa clinical trial to assess the safety, immunogenicity and efficacy of the blood-stage Plasmodium vivax malaria vaccine candidate PvDBPII in Matrix M1 in healthy adults living in the UK
IRAS ID
265494
Contact name
Angela Minassian
Contact email
Sponsor organisation
University of Oxford / Research Governance, Ethics & Assurance
Eudract number
2019-002872-14
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary
Dear VAC079 volunteer, We are writing to update you with the results of the VAC079 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 The initial findings from the study are reported in a pre-print article (preliminary report that has not been peer reviewed) which is available here: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-3D00LL_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJ5EnIbudDkMhwy5UwPjZRWTdIE6Dv-2F0WwZCFVxjLdOCWv03r5TLG0ioQXhPOsEHLXRLb3Rfe3n9Zd7IBOLSCC2iual3UjNEUPBURUYzyIs6dXDQ-2B4YI6K4jGBiLr0ngxpYBmCqWAYPS5jBVu-2FQQKt3VgKwqqJIrGyyHSGRwaa7BQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C22782be24371425f1e4b08db02b7106f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638106757494706874%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=3euELvpW4O5QuNQznC7bC4dxEjv9cTNhfl3rbo3dZzs%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. The results were encouraging and a new trial testing this vaccine is being planned in Thailand.What the study involved:
You were one of 16 adults who took part in the VAC079 study to test a vaccine against Plasmodium vivax malaria. The vaccine is a protein vaccine called “PvDBPII” mixed with an adjuvant called “Matrix-M” that boosts the body’s immune response to the PvDBPII vaccine. PvDBP is a protein that the malaria parasite uses to enter red blood cells and cause malaria. Participants in one study group received 3 vaccinations 1 month apart and then the effectiveness of the vaccine 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). Another study group received 2 vaccinations 1 month apart before the trial was halted for a year due to the Covid-19 pandemic. These participants received a third vaccination about one year later and then underwent malaria infection. These volunteers were invited back to undergo a fourth booster vaccination about 5 months later and then they were infected with malaria for a second time. Participants who underwent malaria infections 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 assess the side effects of the PvDBPII in Matrix-M vaccine in humans
• To assess the body’s immune response to the vaccine
• To assess whether the vaccine slows or stops the growth of malaria parasites in the blood in a malaria challenge, compared with unvaccinated control volunteers
What the study found:
• The PvDBPII in Matrix-M vaccine 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 headaches
• Vaccinations induced antibody responses, which are proteins produced by the immune system. The study group who received a late third vaccination, given 1 year after their first 2 doses, produced higher levels of antibodies compared to the group that received 3 vaccinations 1 month apart. The fourth vaccination boosted antibody responses but not back up to as high a level as after the third delayed vaccination.
• In the study group that received a late third vaccination, during malaria challenge, the rate at which the malaria parasite grew in the blood was reduced by a half and this group took about 1 week longer to develop malaria symptoms compared to unvaccinated control volunteers. The fourth vaccination did not have a significant effect on parasite growth during the second malaria challenge. The participants that received 3 vaccinations 1 month apart also did not show slower growth of malaria during their malaria challenge
• The level of antibody response to the vaccine was related to the speed of parasite growth during malaria challenge – those with higher antibody reponses had slower parasite growth in the blood, which indicates that the antibodies produced to the vaccine are acting on the malaria parasites to stop their replication in the blood
• In those people who had a reduced parasite growth on malaria challenge, a sample of their blood containing antibodies to the vaccine was able to reduce the growth of malaria parasites in the laboratory
What this means:
• Vaccines against P. vivax malaria that target PvDBP have been in development for more than a decade. This is the first study in humans to show that the protein vaccine PvDBPII given with Matrix-M adjuvant can effectively slow the growth of malaria parasites in the blood during malaria challenge
• This effect was only seen in those participants who received a delayed third dose of the vaccine (at about 1 year) and this group also had the highest antibody response to the vaccine indicating that leaving a longer interval between vaccinations can improve the body’s immune response and also the effectiveness of a vaccine
• Measuring the level of the antibody response to a vaccine and how well a blood sample slows the growth of the malaria parasite in the laboratory could be used to estimate how well a vaccine is likely to work in people at preventing malaria. These lab tests could be used to select the best candidate vaccine at an earlier stage of testing to take forward for larger, more expensive clinical trials in people
The reduction in parasite growth seen with the delayed third vaccination was the largest effect seen with any vaccine against the blood stage of malaria infection. However the effect was not big enough to stop parasite growth and all participants still developed malaria. Therefore improvements to this vaccine are required. We will now use blood samples taken in this study to try to work out what aspects of the immune response to the vaccine are associated with effectiveness at preventing parasite growth so we can improve the design of this vaccine to make it better at preventing malaria.
We would like to thank all our participants again for their invaluable contribution towards this study and commitment over the years, 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/0330
Date of REC Opinion
25 Sep 2019
REC opinion
Further Information Favourable Opinion