Page 65 - The lraternational Journal of the Royal Society of Thailand.indd

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

How does RTS,S work? The vaccine triggers an immune response against the
circumsporozoite (CSP) protein, perhaps the dominant antigen of the sporozoite, which
is the first stage in the life cycle of the Plasmodium parasite after the mosquito vector
bites a human host (Regules et al, 2011). The sporozoite stays in the circulation only
for minutes to hours before establishing an infection in the liver where the parasite

matures into merozoites that are released in the bloodstream and are responsible for
morbidity and mortality. The immune response triggered by RTS,S can therefore only
protect against the initial stage in the life cycle of P. falciparum and does not protect

against the blood stages of the parasite. RTS,S consists of virus like particles containing
the C-terminus and central repeat regions of CSP (Regules et al, 2011). The C-terminus
is fused to an HBsAg molecule of the Hepatitis B Virus (HBV) forming an RTS fusion
protein (Figure 1). RTS is co-expressed in Saccharomyces cerevisiae with unmodified
HBsAg which adds the second ‘S’ to RTS,S. When the yeast cells are lysed lipid protein

particles form spontaneously with an RTS to S ratio of 1:4 (Figure 2). The critical CSP
fusion protein makes up only 20% of the active vaccine component. An unintended
but welcomed consequence of this mismatch is the excellent protection against

HBV infection conferred by RTS,S/AS01 (Valea et al, 2020).

Figure 1 A schematic comparison of RTS,S and R21

Borimas Hanboonkunupakarn et al. 57