Page 67 - The lraternational Journal of the Royal Society of Thailand.indd

The International Journal of the Royal Society of Thailand
Volume XV-2023

Evidence that R21/MM is protective comes from a cohort of nearly 500 children
aged 5 to 17 months enrolled in a randomised controlled trial in Nanoro, Burkina Faso.
R21/MM had a favourable safety profile and was well tolerated. Most adverse events
were mild and none of the seven serious adverse events were attributed to the vaccine.
Following the administration of 3 doses of 5 μg R21 plus 50 μg MM, the protective

efficacy was 77% (67 to 84) at 6 months (Datoo et al, 2021). Following a booster dose of
5 μg R21 plus 50 μg MM at Month 12 the protective efficacy was 80% (72 to 85) (Datoo
et al, 2022). These efficacy estimates for R21/MM are better than the RTS,S/AS01

estimates from the large 7-country study (RTSS_Clinical_Trials_Partnership, 2014;
2015). There are several explanations. As mentioned earlier the malaria epidemiology
in the 7 countries is highly heterogeneous and the vaccinations in RTS,S/AS01 trials
were, in contrast to the R21/MM trials, not timed to immediately precede the malaria
season. It should be obvious that for vaccines with rapidly waning protection like

RTS,S/AS01 the estimate of protection changes rapidly over time. Another difference
in the trial design is the coadministration of antimalarial drugs, which may influence
estimates of protection. As many as 80% of the children participating in the R21/MM

trial received antimalarial drugs as part of seasonal malaria chemoprevention routinely
during the follow-up period. On the other hand, during the RTS,S/AS01 trial the
investigators prevented the co- administration of antimalarial drugs for prevention
or treatment of subclinical infections. Today it seems that the coadministration of
antimalarial drugs with vaccinations has additive if not synergistic benefits

(Chandramohan et al, 2021). As mentioned, vaccines targeting the sporozoite stage
in the life cycle of P. falciparum does not impact circulating schizonts. Appropriate
antimalarial drugs are needed to clear these blood stages of P. falciparum. Based onthe

comparison of the R21/MM data from Nanoro, Burkina Faso and the data from
combined SMC and seasonal vaccination trial in Burkina Faso and Mali by Chandramohan
et al (2021). It seems that R21/MM is at least as protective and safe as RTS,S/AS01.
The definitive answer on whether R21/MM is more protective than RTS,S/AS01 would
require a randomised, controlled, double-blind trial comparing the two vaccines

head-to-head, which is unlikely to be forthcoming.

While protective efficacy is critical when selecting a malaria vaccine, availability
is just as relevant. GSK has made it clear that no more than 10 million doses RTS,S/
AS01 will be produced annually, which covers only a fraction of the global demand.
There is talk about a technology transfer to more economic vaccine producers some

years in the future, but this means the vaccine implementation will be delayed and
millions of people continue be exposed to potentially preventable risk. The WHO
has developed a rationing plan prioritizing young African child, who are at highest

Borimas Hanboonkunupakarn et al. 59