The phase 1/2b clinical trial on R21/Matrix-M malaria vaccine has recently reported the safety and efficacy of booster vaccination at 12 months. The entire report has been published in The Lancet Infectious Diseases.
Malaria is one of the leading causes of morbidity and mortality worldwide, with a 12% increase in the number of deaths between 2019 and 2020. The disease is highly prevalent in Africa, where 80% of malaria-related deaths occur in children aged below five years.
RTS,S/AS01 developed by GlaxoSmithKline, is the first malaria vaccine that received approval from the World Health Organization (WHO) to be used in children residing in high transmission regions. The three-dose primary immunization regimen of this vaccine has shown 68% protective efficacy over a period of 6 months. A fourth booster dose administered 18 months after the third dose has shown 44% efficacy against the malaria-causing parasite.
According to the recent guidelines of the Malaria Vaccine Technology Roadmap, new malaria vaccines with at least 75% efficacy against Plasmodium falciparum for more than two years should be licensed by 2030.
In the current double-blind phase 1/2b randomized controlled clinical trial, the safety, immunogenicity, and efficacy of a new malaria vaccine candidate R21/Matrix-M have been determined in children at 12 months post-booster vaccination.
The initial three-dose primary immunization regimen of the Matrix-M-adjuvanted R21 vaccine candidate has shown more than 75% efficacy in African children for a period of 12 months. The fourth booster dose was administered in the same group of children 12 months after the primary vaccination.
Clinical trial design
A previous trial investigating the efficacy of the initial three doses of the vaccine (primary immunization; each dose given 4 weeks apart) had used two different vaccine/adjuvant combinations separately. These combinations included 5 μg R21/25 μg Matrix-M and 5 μg R21/50 μg Matrix-M. The Rabivax-S rabies vaccine was used as control. All vaccinations were done in African children aged 5-17 months before the beginning of malaria season.
In the previous trial, the R21 vaccine with low and high adjuvant doses showed 71% and 77% efficacy at 12 months, respectively.
The fourth booster dose of the R21 vaccine was administered to the same children 12 months after the primary vaccination. A total of 409 children received the booster dose. Of them, 132 received the low adjuvant vaccine, 137 received the high adjuvant vaccine, and 140 received the control vaccine.
The trial findings revealed that compared to the control vaccine, the high adjuvant vaccine has 80% efficacy against clinical malaria at 12 months post-booster vaccination. However, the low adjuvant vaccine showed 71% efficacy.
The low and high adjuvant vaccines showed 61% and 78% protective efficacies against multiple episodes of clinical malaria, respectively.
The estimation of malaria-specific NANP IgG antibody levels 28 days after booster dose administration revealed that both low and high adjuvant booster vaccines helped regain similar antibody levels as observed after the primary vaccination.
Considering both low and high adjuvant groups together, a significant negative correlation was observed between the antibody titers and number of malaria episodes in the first year and second year following booster vaccination.
In both first year and second year, a significant impact of antibody titers was observed on the time to first episode of malaria.
Considering both vaccination groups separately, a similar correlation was observed for the participants who received the high adjuvant booster vaccination. Among these participants, significantly higher antibody titers were observed in those who did not have any malaria episodes during the 2-year follow-up period.
The R21/Matrix-M booster vaccination regimen showed a favorable safety profile and was well-tolerated. During the 12-month follow-up period, three serious adverse events were reported, which were not related to vaccination.
These serious adversities included severe malaria with pneumonia, severe malnutrition with anemia, and bacterial meningitis. Notably, all adversities are resolved eventually.
This clinical trial findings indicate that the R21/Matrix-M booster vaccination can induce robust (80%) and long-lasting (over the period of 2 years) protective efficacy against clinical malaria. The vaccine and its immunization regimen seem to have high potency in controlling highly seasonal malaria transmission in Africa.
The researchers told the BBC that this vaccine can be made for “a few dollars”, and they plan to manufacture over 100 million doses yearly.