Safety, immunogenicity and field efficacy studies of a plasmodium falciparum malaria pre-erythrocytic stage vaccine.

Informacje na temat projektu

Identyfikator umowy o grant: BIO4972164

Projekt został zamknięty

Data rozpoczęcia 1 Września 1997

Data zakończenia 28 Lutego 2001

Finansowanie w ramach

• Specific research, technological development and demonstration programme in the field of biotechnology, 1994-1998

Koszt całkowity

Brak danych

Wkład UE

Brak danych

Koordynowany przez

SMITHKLINE BEECHAM BIOLOGICALS S.A
Belgium

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Rezultaty

Genotyping of parasites in breakthrough cases in RTS,S/AS02 and rabies groups in the main trial and in the booster study

In the main trial 169 individuals with asexual parasitaemia during the surveillance period were genotyped at csp-th2r and csp-th3r (82 in the RTS,S/AS02 group and 87 in the rabies group). Preliminary analysis on protective efficacy against homologous P. falciparum strain (NF54) concentrated on protection against the prevalence of the NF54 allelic type when this allele was present either alone or with others alleles. At csp-th2r, this type was present in 9/77 infections from subjects in RTS,S/AS02 group and 13/80 infections from subjects in the rabies group (P=0.5). At csp-th3r, it was present in 27/77 infections from subjects in RTS,S/AS02 group and 28/80 infections from subjects in the rabies group (P=0.9). This suggests that the protective efficacy of RTS,S/AS02 vaccine is not allele specific. In addition, there was no evidence to suggest that the vaccine protected non-specifically by reducing the frequencies of other allelic types. In the booster study 48 breakthrough cases were genotyped as above. At csp-th2r, the NF54 type was present in 4/19 infections from subjects in RTS,S/AS02 and in 3/29 infections from subjects in the rabies group (P=0.304). At csp-th3r, it was present in 9/19 infections from subjects in RTS,S/AS02 group and in 15/29 infections from subjects in the rabies group (P=0.768). These results confirmed that RTS,S/AS02 vaccine was not allele specific. We have tested if RTS,S/AS02 has an effect on clone carriage. We genotyped breakthroughs in the main trial, and in the booster study at msp1, msp2 and glurp loci. In the main trial the minimum number of clones (MNC) was slightly higher in the RTS,S/AS02 group (3.9) than in the rabies group (3.53) (P=0.064). In the booster study MNC was similar in both groups. MNC increased with parasite densities in both groups (P=0.005) and varied among villages (P=0.009). We found no association of MNC with age or the occurrence malaria symptoms. The molecular characterisation of parasites in breakthrough cases following vaccination with RTS,S/AS02 have added another dimension to the understanding of the molecular mechanisms involved in conferring protection against a specific parasite strain. In these studies we have clearly demonstrated that RTS,S/AS02 vaccine was not allele specific using a novel method that was designed specifically for this studies. The non-allelic protective efficacy of RTS,S/AS02 vaccine allows the testing of this vaccine in transmission settings where the NF54 strain is not the predominant type. Molecular typing should remain an integral part in the design and the evaluation of future malaria vaccine trials in natural setting because it will help us understand the intricate interactions between parasite and host.