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Impact of RTS,S/AS02A and RTS,S/AS01B on genotypes of P. falciparum in adults participating in a malaria vaccine clinical trial

Waitumbi, John N., Anyona, Samuel B., Hunja, Carol W., Kifude, Carolyne M., Polhemus, Mark E., Walsh, Douglas S., Ockenhouse, Chris F., Heppner, D. Gray, Jr., Leach, Amanda J., Lievens, Marc, Ballou, W. Ripley, Cohen, Joe D. and Sutherland, Colin J. (2009). Impact of RTS,S/AS02A and RTS,S/AS01B on genotypes of P. falciparum in adults participating in a malaria vaccine clinical trial. PLoS One,4(11):e7849-1-e7849-8.

Document type: Journal Article
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IRMA ID 75039815xPUB511
Title Impact of RTS,S/AS02A and RTS,S/AS01B on genotypes of P. falciparum in adults participating in a malaria vaccine clinical trial
Author Waitumbi, John N.
Anyona, Samuel B.
Hunja, Carol W.
Kifude, Carolyne M.
Polhemus, Mark E.
Walsh, Douglas S.
Ockenhouse, Chris F.
Heppner, D. Gray, Jr.
Leach, Amanda J.
Lievens, Marc
Ballou, W. Ripley
Cohen, Joe D.
Sutherland, Colin J.
Journal Name PLoS One
Publication Date 2009
Volume Number 4
Issue Number 11
ISSN 1932-6203   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-70849110143
Start Page e7849-1
End Page e7849-8
Total Pages 8
Place of Publication United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DIISR)
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 break-through 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.
DOI http://dx.doi.org/10.1371/journal.pone.0007849   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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