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Katie Collins and Adrian Hill working at the Jenner institute in Oxford recognized that
this mismatch presents an opportunity to improve on RTS,S. They hypothesized that by
increasing the CSP density on the surface of the protein the immune response could be increased.
The International Journal of the Royal Society of Thailand
Volume XV-2023
By switching from S. cerevisiae to Pichia pastoris as expression platform they were able to grow

Katie Collins and Adrian Hill working at the Jenner institute in Oxford
CSP at high density in the presence of an inducible alcohol oxidase AOX1 that ultimately
recognized that this mismatch presents an opportunity to improve on RTS,S. They
hypothesized that by increasing the CSP density on the surface of the protein the
resulted in the expression of an CSP-HBsAg fusion protein without HBsAg excess in R21
immune response could be increased. By switching from S. cerevisiae to Pichia pastoris
as expression platform they were able to grow CSP at high density in the presence of
(Figures 1 & 2) (Collins et al, 2017).
an inducible alcohol oxidase AOX1 that ultimately resulted in the expression of an
CSP-HBsAg fusion protein without HBsAg excess in R21 (Figures 1 & 2) (Collins et al,

2017).

RTS,S R21
RTS,S R21

Figure 2 A schematic presentation of CSP linked to HBsAg in RTS,S and R21

What is the role of the adjuvant? Early studies of RTS,S demonstrated
Figure 2 A schematic presentation of CSP linked to HBsAg in RTS,S and R21
convincingly that the immune response depends on the adjuvant (Gordon et al, 1995).

RTS,S is most immunogenic when administered with AS01 an adjuvant owned by GSK

(Kester et al, 2009). This is a liposome-based adjuvant containing a saponin, QS-21, and
monophosphoryl lipid A, a TLR4 agonist derived from bacterial lipopolysaccharide.
The importance of the adjuvant led critics to speculate that the major commercial
What is the role of the adjuvant? Early studies of RTS,S demonstrated convincingly that
interest that motivated GSK to develop RTS,S was to collect data on AS01 which since
has been critical for the registration of other GSK vaccines including the recombinant
the immune response depends on the adjuvant (Gordon et al, 1995). RTS,S is most immunogenic
‘blockbuster’ varicella-zoster vaccine Shingrix that helped GSK to beat fourth-quarter
profit and sales forecasts in 2022 (Reuters, 2023). The GSK ownership of the intellectual
when administered with AS01 an adjuvant owned by GSK (Kester et al, 2009). This is a
property rights for AS01 makes it unlikely that competing malaria vaccine candidates
can license AS01. Such pragmatic as well as scientific reasons suggested that Matrix M
liposome-based adjuvant containing a saponin, QS-21, and monophosphoryl lipid A, a TLR4
(MM) licensed from Novavax, composed of saponins, cholesterol, and phospholipids
agonist derived from bacterial lipopolysaccharide. The importance of the adjuvant led critics to
is the most appropriate adjuvant for R21.

speculate that the major commercial interest that motivated GSK to develop RTS,S was to

58
The First Licensed Malaria Vaccines: From RTS,S to R21
collect data on AS01 which since has been critical for the registration of other GSK vaccines

including the recombinant ‘blockbuster’ varicella-zoster vaccine Shingrix that helped GSK to

beat fourth-quarter profit and sales forecasts in 2022 (Reuters, 2023). The GSK ownership of the

intellectual property rights for AS01 makes it unlikely that competing malaria vaccine candidates

can license AS01. Such pragmatic as well as scientific reasons suggested that Matrix M (MM)

licensed from Novavax, composed of saponins, cholesterol, and phospholipids is the most

appropriate adjuvant for R21.

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