PRJNA235895
RTS,S Phase III Malaria Vaccine Trial Genotyping
The GlaxoSmithKline (GSK) Phase III RTS,S/AS01E malaria vaccine trial will evaluate the efficacy of the RTS,S candidate vaccine against malaria disease caused by Plasmodium falciparum infection, across diverse malaria transmission settings in Africa. A portion of this vaccine’s antigen consists of sequence from the P. falciparum circumsporozoite protein (CSP). Natural selection by the host immune system has given rise to high levels of antigenic variation at the CSP locus within many P. falciparum populations. It is hypothesized that administration of a candidate vaccine containing CSP antigens could also induce selection for existing or novel antigenic CSP variants. The goal of this genotyping study is therefore to determine if RTS,S/AS01E selects specific parasite variants or alters the number of parasite types within a vaccinated subject and to gain a better understanding of the mechanism of action of the RTS,S/AS01E candidate vaccine. We have generated deep PCR-based Illumina MiSeq data for the T epitope region of the CSP locus as well as two comparably polymorphic loci not included in the vaccine (TRAP and SERA2) from approximately 5200 patient samples. From the same sample set, we have also generated PCR-based PacBio sequence data from a longer amplicon spanning the repeat region of the CSP locus.