* VAC084:safety and immunogenicity of Pvs25-IMX313/Matrix-M1 vaccine
Research type
Research Study
Full title
A Phase Ia study to assess safety and immunogenicity of the Plasmodium vivax malaria vaccine candidate Pvs25-IMX313 in Matrix-M1 adjuvant in healthy adults living in the UK
IRAS ID
302239
Contact name
Angela Minassian
Contact email
Sponsor organisation
University of Oxford, RGEA
Eudract number
2021-003550-23
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 11 months, 8 days
Research summary
Research Summary
Pvs25-IMX313/Matrix-M1 is a new ‘transmission-blocking vaccine’ for malaria. The vaccine aims to cause the body to produce an immune response which blocks the malaria parasite developing in the mosquito, so that when the mosquito next bites, it cannot infect another person with malaria. This means that unlike other vaccines, Pvs25-IMX313/Matrix-M1 does not aim to protect the person being vaccinated from disease, but instead to reduce risk of infection to other people. In this way, if effective, a transmission-blocking vaccine could stop onward transmission of malaria and bring down the number of cases in the whole population.
In this study, the Pvs25-IMX313/Matrix-M1 vaccine will be given to people for the first time. The purpose of this study is to assess the safety of Pvs25-IMX313/Matrix-M1, as well as the body’s immune response to the vaccine. We will do this by giving volunteers three doses of the vaccine, at four week intervals, doing blood tests and collecting information about any symptoms that occur after vaccination. We plan to recruit a total of 24-30 volunteers to be vaccinated.
Summary of Results
Why was this study needed?
Malaria remains a major global public health problem with an estimated 249 million cases of malaria occurring worldwide in 2022. Malaria is caused by different species of the Plasmodium parasite which are spread by the Anopheles mosquito. Plasmodium vivax (P. vivax) is the second most common cause of malaria worldwide and is the leading cause of malaria in Asia and South America.
P. vivax has long been considered a ‘benign’ form of malaria. However, it has recently been shown to cause significant health problems, such as breathing, kidney and blood problems, and some deaths. P. vivax infection during pregnancy has also been shown to lead to the delivery of lower birth weight infants despite effective antimalarial treatment. The overall global cost of P. vivax malaria is estimated at US$ 1.4 to 4.0 billion per year, and those affected by this infection often have inadequate access to affordable healthcare and with little financial reserve, perpetuating the cycle of poverty. In light of this, recent calls for control and ‘eradication’ of malaria worldwide have focused attention on this neglected disease and the need for development of an effective vaccine to be used alongside current control methods.
One vaccination strategy is to prevent the malaria parasite from being transmitted from one person to the next by preventing the parasite from replicating within the mosquito. This is what transmission-blocking vaccines aim to do. When a mosquito bites an individual who has received this vaccine, the expectation is that it will ingest the vaccine-induced antibodies present within the individual’s blood, which then prevent the parasite from replicating in the mosquito, and therefore, prevent the parasite from being transmitted to the next person the mosquito bites. Importantly, transmission-blocking vaccines do not directly protect the person who has been vaccinated from disease, but aim to provide community-level protection against the disease by reducing the number of mosquitoes that are able to transmit the infection. It is hoped that this vaccine strategy, in addition to other control methods in development, will help to reduce the burden of this disease globally.
What did the trial involve?The antigen that was being assessed during this trial was called Pvs25-IMX313. It was administered alongside an adjuvant (a protein which helps to boost the immune response to the vaccine) called Matrix-M, which is already used in a number of licensed vaccines. This trial was the first time the Pvs25-IMX313 antigen was administered to humans.
The trial consisted of three groups of eight participants (24 participants in total). You were each assigned to one of three groups in which you received three doses of the Pvs25-IMX313/Matrix-M vaccine at varying doses at different time points, with a 28 day follow up period after each vaccination. Unfortunately, due to circumstances outside of our control, two participants in Group 2 and two participants in Group 3 only received two doses of the vaccine, however, all other participants received the full course of three vaccine doses.
The main aim of the study was to determine whether the vaccine was safe and well-tolerated within these three different dosing regimens. We also wanted to find out which regimen stimulated the greatest and longest lasting antibody response.
What were the aims of the trial?
The aims of the trial were:
• To collect information about local signs and symptoms around the vaccination site (arm) that were experienced by participants within seven days of receiving each vaccination.
• To collect information about systemic signs and symptoms experiences by participants within seven days of receiving each vaccination.
• To collect information about any other symptoms or untoward events experienced by participants within 28 days of receiving each vaccination.
• To determine whether the vaccine caused a change in any of the blood markers of general health monitored during the trial within 28 days of receiving each vaccination.
• To collect information about any serious illnesses or events experienced by participants throughout the whole duration of the trial.We achieved these aims by analysing your diary entries, as well as the results of the blood samples you provided us with during your study visits.
The trial also aimed to provide an indication of whether the antibodies produced by this vaccine would be effective at interrupting the replication of P. vivax in the mosquito. We assessed this using the blood samples you gave us after being vaccinated as they contain these all-important antibodies. These were then used to “feed” live mosquitoes and the subsequent development of P. vivax parasites in the mosquito midgut was assessed.
What did the trial find?
The main findings of the trials were:
• Receiving up to three doses of the Pvs25-IMX313/Matrix-M vaccine is well-tolerated.
• The most common symptom noted at the site of the vaccination within the first seven days of receiving the vaccine was pain, however, this was mostly mild and resolved within 5 days of receiving the vaccine for all participants.
• The most common systemic symptom notes within the first seven days of receiving the vaccine was fatigue, which was also mostly mild.
• Receiving the Pvs25-IMX313/Matrix-M vaccine did not cause any significant abnormality of any blood markers of general health within 28 days.
• Importantly, no serious illnesses/events were found to be associated with the Pvs25-IMX313/Matrix-M vaccine.
• Receiving three doses of the Pvs25-IMX313/Matrix-M vaccine resulted in large numbers of antibodies being produced, targeting Pvs25.
• Mosquito feeding experiments are still ongoing but in the initial results, antibodies from the majority of trial participants were able to significantly reduce the number of mosquitoes becoming infected upon feeding on P. vivax infected blood.What does this mean going forward?
The results of this trial showed that the Pvs25-IMX313/Matrix-M vaccine is well-tolerated with no serious events experienced by participants as a result of the vaccine, and mainly mild symptoms related to receiving the vaccine. This trial was an important first step in understanding how this transmission-blocking vaccine could be best used to interrupt the transmission of P. vivax malaria infection and provided preliminary evidence to support its safe use in humans.
In our next body of work, we will be looking at how we can use this vaccine in combination with other types of malaria vaccine which directly prevent malaria infection to determine whether a combination vaccine is more effective at preventing this disease than a single vaccine approach.
REC name
South Central - Oxford A Research Ethics Committee
REC reference
22/SC/0308
Date of REC Opinion
13 Jan 2022
REC opinion
Favourable Opinion