Strain-Specific Humoral Response to a Polymorphic Malaria Vaccine
2004; American Society for Microbiology; Volume: 72; Issue: 11 Linguagem: Inglês
10.1128/iai.72.11.6300-6305.2004
ISSN1098-5522
AutoresChristian Flück, Thomas Smith, Hans‐Peter Beck, Andrea Irion, Inoni Betuela, Michael P. Alpers, Robin F. Anders, Allan Saul, Blaise Genton, Ingrid Felger,
Tópico(s)Computational Drug Discovery Methods
ResumoThe 3D7 form of the merozoite surface protein 2 (MSP2) of Plasmodium falciparum was one of three subunits of the malaria vaccine Combination B that were tested in a phase I/IIb double-blind randomized placebo-controlled trial, which was undertaken with 120 Papua New Guinean children of 5 to 9 years of age. Because only one variant of the highly polymorphic MSP2 was used for vaccination, we examined whether the elicited response was directed against conserved or strain-specific epitopes. Postvaccination (week 12) titers of antibody against recombinantly expressed individual domains of MSP2 were measured by enzyme-linked immunosorbent assay and compared to baseline values. We found that vaccination with the 3D7 form of MSP2 induced a significant strain-specific humoral response directed against the repetitive and semiconserved family-specific part. The conserved N- and C-terminal domains were not immunogenic. Titers of antibody against the alternate FC27 family-specific domain showed a tendency to increase in vaccinated children, but there was no increase in antibodies against FC27-type 32-mer repeats. These results indicate that vaccination with one MSP2 variant mainly induced a strain-specific response, which can explain the selective effect of vaccination with combination B on the genotypes of breakthrough parasites. These findings support the inclusion of both family-specific domains (3D7 and FC27) in an improved vaccine formulation.
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