Scientists at the University of Oxford develop a Malaria vaccine that gives up to 80% protection

Scientists at the University of Oxford develop a Malaria vaccine that can give up to 80% protectionThe team now expect it to be rolled out next year after the successful trials. In addition to the effectiveness of the vaccine, it is cheap and an agreement exists to manufacture more than 100 million doses a year. The charity Malaria No More said recent progress meant children dying from malaria could end “in our lifetimes”.

It has taken more than a century to develop effective vaccines as the malaria parasite, which is spread by mosquitoes, is spectacularly complex and elusive. It is a constantly moving target, shifting forms inside the body, which make it hard to immunize against.

Trial results from 409 children in Nanoro, Burkina Faso, have been published in the Lancet Infectious Diseases. It shows three initial doses followed by a booster a year later gives up to 80% protection.


Summary of the published study:

Background

Malaria is a leading cause of morbidity and mortality worldwide. We previously reported the efficacy of
the R21/Matrix-M malaria vaccine, which reached the WHO-specified goal of 75% or greater efficacy over 12 months
in the target population of African children. Here, we report the safety, immunogenicity, and efficacy results at
12 months following administration of a booster vaccination.

Methods

This double-blind phase 1/2b randomised controlled trial was done in children aged 5–17 months in Nanoro,
Burkina Faso. Eligible children were enrolled and randomly assigned (1:1:1) to receive three vaccinations of either
5 µg R21/25 µg Matrix-M, 5 µg R21/50 µg Matrix-M, or a control vaccine (the Rabivax-S rabies vaccine) before the
malaria season, with a booster dose 12 months later. Children were eligible for inclusion if written informed consent
could be provided by a parent or guardian. Exclusion criteria included any existing clinically significant comorbidity
or receipt of other investigational products. A random allocation list was generated by an independent statistician by
use of block randomisation with variable block sizes. A research assistant from the University of Oxford, independent
of the trial team, prepared sealed envelopes using this list, which was then provided to the study pharmacists to
assign participants. All vaccines were prepared by the study pharmacists by use of the same type of syringe, and the
contents were covered with an opaque label. Vaccine safety, efficacy, and a potential correlate of efficacy with
immunogenicity, measured as anti-NANP antibody titres, were evaluated over 1 year following the first booster
vaccination. The population in which the efficacy analyses were done comprised all participants who received the
primary series of vaccinations and a booster vaccination. Participants were excluded from the efficacy analysis if they
withdrew from the trial within the first 2 weeks of receiving the booster vaccine. This trial is registered with
ClinicalTrials.gov (NCT03896724), and is continuing for a further 2 years to assess both the potential value of
additional booster vaccine doses and longer-term safety.

Findings

Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each child received the
same vaccination for the booster as they received in the primary series of vaccinations; 132 participants received 5 µg
R21 adjuvanted with 25 µg Matrix-M, 137 received 5 µg R21 adjuvanted with 50 µg Matrix-M, and 140 received the
control vaccine. R21/Matrix-M had a favourable safety profile and was well tolerated. Vaccine efficacy remained high in
the high adjuvant dose (50 µg) group, similar to previous findings at 1 year after the primary series of vaccinations.
Following the booster vaccination, 67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant,
54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who
received the rabies vaccine developed clinical malaria by 12 months. Vaccine efficacy was 71% (95% CI 60 to 78) in the
low-dose adjuvant group and 80% (72 to 85) in the high-dose adjuvant group. In the high-dose adjuvant group, vaccine
efficacy against multiple episodes of malaria was 78% (95% CI 71 to 83), and 2285 (95% CI 1911 to 2568) cases of
malaria were averted per 1000 child-years at risk among vaccinated children in the second year of follow-up. Among
these participants, at 28 days following their last R21/Matrix-M vaccination, titres of malaria-specific anti-NANP
antibodies correlated positively with protection against malaria in both the first year of follow-up (Spearman’s ρ –0·32
[95% CI –0·45 to –0·19]; p=0·0001) and second year of follow-up (–0·20 [–0·34 to –0·06]; p=0·02).

Interpretation

A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen maintained high
efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine induced antibody
concentrations that correlated with vaccine efficacy. The trial is ongoing to assess long-term follow-up of these
participants and the value of further booster vaccinations.

Funding European and Developing Countries Clinical Trials Partnership 2 (EDCTP2), Wellcome Trust, and NIHR
Oxford Biomedical Research Centre

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