RESUMO
BACKGROUND: Plasmodium falciparum merozoite surface protein-1 (MSP1) has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17) and the hypervariable N-terminal repeat region (block 2). However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene. METHODS: The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7) in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition. RESULTS: IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%), with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations. CONCLUSIONS: Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important in isolate-specific immunity to P. falciparum.
Assuntos
Epitopos/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Malária Falciparum/imunologia , Proteína 1 de Superfície de Merozoito/genética , Plasmodium falciparum/imunologia , Adolescente , Adulto , Idoso , Alelos , Anticorpos Antiprotozoários/genética , Anticorpos Antiprotozoários/imunologia , Camarões , Criança , Pré-Escolar , Colômbia , Reações Cruzadas/genética , Reações Cruzadas/imunologia , Epitopos/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Imunoglobulina G/genética , Imunoglobulina M/genética , Lactente , Malária Falciparum/transmissão , Masculino , Proteína 1 de Superfície de Merozoito/imunologia , Proteína 1 de Superfície de Merozoito/metabolismo , Pessoa de Meia-Idade , Papua Nova Guiné , Plasmodium falciparum/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Adulto JovemRESUMO
The merozoite surface protein 1 (MSP-1) gene of Plasmodium falciparum encodes a major immune target under development as a malaria vaccine. In this study, we typed MSP-1 variable regions of parasites obtained from Buenaventura, Colombia. Four MSP-1 gene types were detected corresponding to prototype and recombinant K1 and MAD20 block 4 sequences. In contrast to variability within block 4, blocks 2, 6, and 16-17 corresponded exclusively to the MAD20 allelic type. Most (80%) blood samples contained multiple MSP-1 gene types. The presence of four MSP-1 variants within block 4 against a MAD20 background indicates that current P. falciparum populations in Buenaventura are derived from parasites expressing K1 and MAD20 alleles, some of which underwent two recombination events within or flanking block 4. Restricted MSP-1 diversity appears to be relatively stable in Buenaventura and suggests that selection has resulted in the dominance of the MAD20 type in most of the polymorphic blocks with the exception of block 4.