Abstract:
Objective: RTS,S, a candidate vaccine for malaria, is a recombinant protein expressed in yeast containing part of the
circumsporozoite protein (CSP) sequence of 3D7 strain of Plasmodium falciparum linked to the hepatitis B surface antigen in
a hybrid protein. The RTS,S antigen is formulated with GSK Biologicals’ proprietary Adjuvant Systems AS02A or AS01B. A
recent trial of the RTS,S/AS02A and RTS,S/AS01B vaccines evaluated safety, immunogenicity and impact on the development
of parasitemia of the two formulations. Parasite isolates from this study were used to determine the molecular impact of
RTS,S/AS02A and RTS,S/AS01B on the multiplicity of infection (MOI) and the csp allelic characteristics of subsequent
parasitemias.
Design: The distribution of csp sequences and the MOI of the infecting strains were examined at baseline and in breakthrough
infections from vaccinated individuals and from those receiving a non-malarial vaccine.
Setting: The study was conducted in Kombewa District, western Kenya.
Participants: Semi-immune adults from the three study arms provided isolates at baseline and during break-through
infections.
Outcome: Parasite isolates used for determining MOI and divergence of csp T cell–epitopes were 191 at baseline and 87
from break-through infections.
Results: Grouping recipients of RTS,S/AS01A and RTS,S/AS02B together, vaccine recipients identified as parasite-positive by
microscopy contained significantly fewer parasite genotypes than recipients of the rabies vaccine comparator (median in
pooled RTS,S groups: 3 versus 4 in controls, P = 0.0313). When analyzed separately, parasitaemic individuals in the RTS,S/
AS01B group, but not the RTS,S/AS02A group, were found to have significantly fewer genotypes than the comparator group.
Two individual amino acids found in the vaccine construct (Q339 in Th2R and D371 in Th3R) were observed to differ in
incidence between vaccine and comparator groups but in different directions; parasites harboring Q339 were less common
among pooled RTS,S/AS vaccine recipients than among recipients of rabies vaccine, whereas parasites with D371 were more
common among the RTS,S/AS groups.
Conclusions: It is concluded that both RTS,S/AS vaccines reduce multiplicity of infection. Our results do not support the
hypothesis that RTS,S/AS vaccines elicit preferential effects against pfcsp alleles with sequence similarity to the 3D7 pfcsp
sequence employed in the vaccine construct.