Changing dosing schedule may improve malaria vaccine efficacy

Changing dosing schedule of a malaria vaccine candidate can improve its efficacy to about 87 per cent, compared with 63 per cent using the current standard regimen, a new study has found.
The study was conducted at the Walter Reed Army Institute of Research (WRAIR) in the US in 30 malaria-naive adults, using the controlled human malaria infection model (CHMI), also referred to as the malaria challenge model.
Malaria continues to have a devastating global impact, infecting more than 200 million people annually and killing an estimated 438,000 - most of them young children - in 2015.
The RTS,S/AS01 malaria vaccine candidate - developed in the early 1980s - is the first vaccine to successfully complete a pivotal large-scale phase 3 trial in Africa.

The paediatric RTS,S/AS01 vaccine candidate has been positively reviewed by the European Medicines Agency (EMA) and recommended for pilot implementation in sub-Saharan Africa by the World Health Organisation (WHO) to determine its potential real-world application.
This regimen has been shown to reduce cases of malaria by about half over 18 months of follow-up in children 5 to 17 months at first vaccination, and the administration of a fourth dose at 18 months results in an about 40 per cent reduction in cases over four years of follow-up. Its ability to protect against malaria waned over time.

In light of the partial efficacy profile of RTS,S/AS01, scientists have continued investigating a variety of strategies to improve the absolute level of the vaccine's efficacy.

In the new study, researchers sought to determine if a novel immunisation schedule, specifically delaying RTS,S/AS01 administration and reducing dosage of the third vaccination, as well as any following booster dose, would significantly increase the candidate vaccine's ability to protect against infection.
As part of the study, conducted by WRAIR and involving malaria-naive adult US volunteers, researchers immunised study participants according to two regimens: a 0, 1, 7 month schedule with a fractional third dose (Fx017M) and the current standard 0, 1, 2 month schedule (012M).
Following the third vaccination, study participants were exposed to malaria-causing parasites, using CHMI, and the extent to which each regimen protected against infection was determined.

The efficacy of an additional fractional dose, or booster, in protecting against a second CHMI was then assessed.
Twenty-six of 30 study participants (86.7 per cent) who received the Fx017M regimen and 10 of 16 (62.5 per cent) who received the 012M regimen were protected from infection following the first CHMI.
The Fx017M regimen delayed infection longer when compared to the 012M regimen, as well.
About 90 per cent of the Fx017M group, who received a 4th fractional 'booster' dose and underwent the second CHMI, were protected from infection.
The research was published in the Journal of Infectious Diseases.