VAC066 - An efficacy study of IV boosting with ChAd63/MVA ME-TRAP
Research type
Research Study
Full title
A Phase I/IIa Sporozoite Challenge Study to assess the safety, immunogenicity and protective efficacy of intravenous boosting with malaria vaccine candidates ChAd63 and MVA encoding ME-TRAP
IRAS ID
245537
Contact name
Adrian V.S. Hill
Contact email
Sponsor organisation
University of Oxford, CTRG
Eudract number
2017-001075-23
Duration of Study in the UK
1 years, 2 months, 29 days
Research summary
Research Summary
Plasmodium falciparum Malaria remains a major global health problem with approximately 200 million cases and 500,000 deaths worldwide annually, mostly in African infants. Current malarial control strategies are threatened by emergence of parasite resistance to drug treatment and resistance of the mosquito vector to certain insecticides. A deployable malaria vaccine is therefore a key strategy for reducing malaria mortality and progressing towards global eradication, but those in clinical trials are currently someway short of WHO targets.
ChAd63 ME-TRAP and MVA ME-TRAP are leading candidate vaccines being developed by Adrian Hill’s group at the University of Oxford, and collaborators. Since 2007, testing of these vaccines intramuscularly in over 900 volunteers has shown them to be safe, well tolerated and capable of delivering partial efficacy against malaria infection. This study will be the first time studying the efficacy of giving a boosting dose of the vaccines intravenously in what we call a “prime-target” strategy. It follows very encouraging pre-clinical work showing this route can target desirable immune responses to the liver to fight a crucial stage of malaria infection. An ongoing recent phase I study is dose escalating both these vaccines intravenously as a single dose prior to commencing this trial where intramuscular and intravenous doses will be combined for the first time. We will initially recruit 46 healthy UK adult volunteers who will be enrolled into 4 vaccination arms (10 volunteers each) and an unvaccinated control group (6 volunteers) who will undergo a controlled human malaria infection (CHMI). These are standardised, carefully supervised infection experiments used internationally to assess vaccine efficacy. As this is the first time giving intramuscular and intravenous doses of these vaccines in a combined schedule, we will closely profile the safety and immune response during the vaccination follow-up. All trial activity will take place in Oxford.Summary of Results
THANK YOU!
The University of Oxford and the study team thank all the participants for taking part in this clinical study. You helped us, the researchers, learn more about the two malaria vaccine candidates, ChAd63 ME-TRAP and MVA ME-TRAP.
We would like to share the results of this study with you. We hope this summary of the study results helps you to understand, and feel proud of, your key role in medical research. If you have questions about the results, please contact the study team.Study Full Title: A Phase I/IIa Sporozoite Challenge Study to assess the safety, immunogenicity and protective efficacy of intravenous boosting with malaria vaccine candidates ChAd63 and MVA encoding ME-TRAP
Short Title: A study to assess the effectiveness of novel malaria vaccine candidates by infecting vaccinated volunteers with malaria parasites
Who carried out the research?
The study was carried out by researchers at the University of Oxford.What public involvement there was in the study?
42 healthy volunteers were recruited for the study. 36 volunteers received at least one experimental malaria vaccine and 6 volunteers did not receive any vaccines. 34 volunteers received an intravenous vaccine (vaccine injected directly into the veins). 36 volunteers were included in the malaria challenge part of the study.Where and when the study took place?
The study took place in the UK at three sites: Oxford, London and Southampton. All participants were followed up in Oxford for the duration of the malaria challenge follow up period.Why was the research needed?
Malaria kills large numbers of people every year. A highly effective vaccine could save many lives.What were the main questions studied?
The study was performed to check whether a course of the experimental vaccines was safe and could protect people against deliberate infection with malaria and was able to make an immune response against malaria.Who participated in the study?
12 females and 30 males participated in the study. The ages of volunteers ranged from 18 to 45. All volunteers had a medical assessment to check they met the study requirements before taking part. Most volunteers were recruited in Oxford. Two volunteers were recruited at the trial site in London and one volunteer in Southampton.What treatments or interventions did the participants take/receive?
Four different combinations of experimental malaria vaccines were tested in the study. Each course involved a combination of vaccines given as conventional vaccines into the muscle and a final vaccine given directly into a vein (intravenous). The vaccines are made from genetically modified viruses that cannot reproduce themselves and are called ChAd63 ME-TRAP and MVA ME-TRAP.What medical problems (adverse reactions) did the participants have?
Post vaccination symptoms were common in the 72-hour period following vaccinations. Multiple participants graded post-vaccination side effects such as “feverishness” as severe following intravenous vaccination. All of these reactions were short lived and mostly resolved by 72 hours. Side effects around the injection site (i.e. pain) were very low following intravenous vaccination. Elevated liver blood enzymes were found to be temporarily raised to high levels in a small proportion of volunteers although these returned to normal levels soon afterwards. Other markers of liver health remained normal. No serious reactions occurred.What happened during the study?
Participants were recruited to receive a series of experimental malaria vaccines over 1 or 2 months and to attend follow up visits to collect blood samples. They also completed online symptom diaries to collect safety data. Most were subsequently exposed to the malaria parasite by allowing malaria infected mosquitos to bite their arms in controlled conditions. A control group was also recruited, who did not receive any vaccines. Participants were intensively followed up after malaria exposure to see if they developed malaria. A subset of volunteers agreed to allow cells to be sampled directly from their liver using an ultrasound guided needle to allow testing of immune cells in the liver.What were the results of the study?
The vaccines were able to generate high levels of malaria-targeting specialised immune cells. We were also able to show these cells were detectable in the liver. A secondary analysis showed evidence that one of the combinations of vaccines may prevent malaria infection. On the main analysis no significant differences were seen in the number of individuals developing malaria in the control group compared to the vaccine groups. Substantial rises in liver enzymes were seen in a small number of volunteers although these rapidly returned to normal levels. Post-vaccination side effects were common and included some symptoms graded by participants as severe although these resolved rapidly. Intravenous vaccines did not lead to any serious adverse reactions.How has this study helped patients and researchers?
This study has shown that intravenous vaccination is able to generate high levels of a targeted immune response. This may represent a way to enhance the power of existing or future vaccines.Details of any further research planned
Further combinations of vaccines and intravenous doses should be trialled in the future.Where can I learn more about this study?
The full study results will be published in a scientific journal shortly.REC name
South Central - Oxford A Research Ethics Committee
REC reference
18/SC/0384
Date of REC Opinion
17 Aug 2018
REC opinion
Favourable Opinion