RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection.
OBJECTIVE
The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes.


METHODS
P. falciparum DNA from isolates collected during the trial was used for genotype studies.


METHODS
The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004.


METHODS
Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection.


RESULTS
Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined.


RESULTS
We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478).


CONCLUSIONS
RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.
Enosse
Sonia
S
Centro de Investigação em Saúde da Manhiça, Ministério de Saúde, Maputo, Mozambique.
Dobaño
Carlota
C
Quelhas
Diana
D
Aponte
John J
JJ
Lievens
Marc
M
Leach
Amanda
A
Sacarlal
Jahit
J
Greenwood
Brian
B
Milman
Jessica
J
Dubovsky
Filip
F
Cohen
Joe
J
Thompson
Ricardo
R
Ballou
W Ripley
WR
Alonso
Pedro L
PL
Conway
David J
DJ
Sutherland
Colin J
CJ