*VAC085: safety and immunogenicity of Pfs48/45 in Matrix-M vaccine
Research type
Research Study
Full title
A Phase Ia study to assess safety and immunogenicity of the Plasmodium falciparum malaria vaccine candidate Pfs48/45 in Matrix-M adjuvant in healthy adults living in the UK
IRAS ID
1004817
Contact name
Anglea Minassian
Contact email
Sponsor organisation
University of Oxford
Eudract number
2021-006763-26
Clinicaltrials.gov Identifier
Research summary
Research Summary
Pfs48/45 in Matrix-M 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, Pfs48/45 in Matrix-M 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 Pfs48/45 in Matrix-M vaccine will be given to people for the first time. The purpose of this study is to assess the safety of the vaccine, as well as the body’s immune response to it. We will do this by giving volunteers three doses of the vaccine, at four-weekintervals, 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
Malaria, caused by dierent species of the Plasmodium parasite which are spread by the Anopheles mosquito, remains a major global public health problem. An estimated 249 million cases of malaria and over 600,000 deaths occurred worldwide in 2022. Plasmodium falciparum (P. falciparum) is associated with 99% of malaria-related deaths in the African region.
The malaria parasite spreads by replicating inside the gut of the mosquito that has taken it up and is then passed onto another person when that mosquito bites again. Transmission-blocking vaccines help the immune system create antibodies against a protein needed for parasite replication. When a mosquito bites a vaccinated individual, it takes up these antibodies which prevent the replication process, thereby prevent malaria transmission.
Transmission-blocking vaccines do not directly protect the person who has been vaccinated but aim to provide community-level protection against the disease by reducing the number of mosquitoes that are able to spread the infection. Pfs48/45, the target protein in this trial, is involved in the replication of the malaria parasite. This trial was the rst time that Pfs48/45 has been administered to humans. Pfs48/45 was administered alongside an adjuvant (a substance which helps to boost the immune response to the vaccine) called Matrix-M™, which is already used in several licensed vaccines.
The trial planned to enrol 24 healthy, malaria naïve adults into 3 groups of 8. All participants were vaccinated on days 0, 28, and 56, with a 28-day follow-up period after each vaccination. Participants in group 1 received three doses 10μg of Pfs48/45, those in group 2 received three doses 50μg of Pfs48/45, and those in group 3 received two doses of 50μg Pfs48/45 and a nal dose of 10μg Pfs48/45. All vaccinations were given with 50μg Matrix-M™.
Unfortunately, due to administrative delays with vaccine supplies, only 17 volunteers were enrolled in total across the three groups, and some volunteers in groups 2 and 3 did not receive all three doses of the vaccine.
The main aim of the study was to determine whether the vaccine was safe and well-tolerated within these three different dosing schedules. We also wanted to find out which dosing schedule stimulated the greatest and longest lasting antibody response. The aims of the trial were to collect information about:
Expected local signs and symptoms around the vaccination site that were experienced by volunteers within 7 days of receiving each vaccination (‘local solicited adverse events’). Expected systemic (general) signs and symptoms experiences by participants within 7 days of receiving each vaccination (‘systemic solicited adverse events’).
Any other symptoms or untoward adverse events experienced by volunteers within 28 days of receiving each vaccination (‘unsolicited adverse events’).
Whether the vaccine caused a change in any of the blood tests or general health of volunteers during the trial within 28 days of receiving each vaccination (‘laboratory adverse events’).
Any serious adverse events experienced by participants throughout the whole duration of the trial. (Serious adverse events are those resulting in death, hospitalisation or prolongation of existing hospitalisation, persistent or significant disability/incapacity or a congenital anomaly or birth defect).
We achieved these aims by analysing diary entries, information provided at follow-ups, and blood samples provided during study visits. The trial also aimed to investigate whether the antibodies produced by this vaccine would be effective at interrupting the replication of P. falciparum malaria in the mosquito. We assessed this using the blood samples that were given after vaccination, which contained these antibodies. These were then used to “feed” live mosquitoes in a lab setting, to assess the development of malaria parasites in the mosquito’s gut.
The main findings of the trials were:
Receiving up to three doses of the Pfs48/45 in Matrix-M™ vaccine is well-tolerated.
No serious adverse events were reported during the trial. Most solicited adverse events reported were mild or moderate in severity and resolved without intervention.
Receiving three doses of the Pfs48/45 in Matrix-M™ vaccine resulted in significant induction of antibodies targeting the Pfs48/45 protein.
Laboratory analysis is still ongoing, but the initial results show that the antibodies from most trial volunteers were able to significantly reduce the number of mosquitoes infected with the parasite after these mosquitos were exposed to blood infected with P. falciparum malaria.
The profile of adverse events reported in this trial is similar to other soluble protein vaccines. This trial was an important first step in understanding how this transmission-blocking vaccine could be best used to interrupt the transmission of P. falciparum malaria infection and provided initial evidence to support its safe use in humans.REC name
South Central - Oxford A Research Ethics Committee
REC reference
22/SC/0291
Date of REC Opinion
13 May 2022
REC opinion
Further Information Favourable Opinion