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Fine specificity of anti-MSP119 antibodies and multiplicity of Plasmodium falciparum merozoite surface protein 1 types in individuals in Nigeria with sub-microscopic infection.

Ngoundou-Landji J, Nwuba RI, Anumudu CI, Odaibo AB, Matondo Maya WD, Awobode HO, Okafor CM, Morenikeji OA, Asinobi A, Nwagwu M, Holder AA, Ntoumi F - Malar. J. (2010)

Bottom Line: The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples.Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10.Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04).

View Article: PubMed Central - HTML - PubMed

Affiliation: 1Université des Sciences et Techniques de Masuku, Franceville, Gabon.

ABSTRACT

Background: The absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP119) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP119 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study.

Methods: Plasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured.

Results: Plasma samples from 85% of individuals contained antibodies that bound to MSP119. The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04).

Conclusions: In the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection.

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Distribution and prevalence of MSP1 alleles within sequence block 2 that were identified in the cross sectional survey. The different alleles fall into 3 different sequence families (RO33, MAD20, and K1) within which there are size polymorphisms identified by the size of the PCR amplified fragment (shown in base pairs, bp)
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Figure 1: Distribution and prevalence of MSP1 alleles within sequence block 2 that were identified in the cross sectional survey. The different alleles fall into 3 different sequence families (RO33, MAD20, and K1) within which there are size polymorphisms identified by the size of the PCR amplified fragment (shown in base pairs, bp)

Mentions: It was of interest to determine whether or not multiplicity of infection (MOI), and the numbers of different MSP1 types affected either the total amount of MSP119-specific antibody or of antibody that competed with the mAbs, and therefore the number of msp1 sequence block 2 types in the samples was used as a marker for MOI and MSP1 polymorphism in each individual. Genotyping of the polymorphic sequence block 2 revealed that RO33 was the predominant allele with 57% of the total, with the K1 and MAD20 allelic families representing 26% and 17%, respectively. Based on size polymorphism, only one RO33 allele was detected whereas the MAD20 and K1 families contained 8 and 13 distinct alleles, respectively (Figure 1). There was no preferential distribution of allelic families between age-groups. The mean minimum MOI based on the number of msp1 genotypes detected for individuals in each age-group is shown in Table 2. The highest MOI was found in the 6 to 15 years age group. Seventy-three of 147 (51%) isolates were found to have more than one P. falciparum genotype. There was no significant influence of age on the proportion of individuals with multiple versus single infections (denoted by M and S, respectively in Table 2) or on MOI. Overall, no correlation between MOI and the mean log titre of anti-MSP119 antibodies was detected. Similarly the MOI was not correlated with inhibition of mAb 12.10 binding. However, comparing the two groups M (multiple infection) and S (single infection), there was a higher prevalence of antibodies that competed with mAb 12.10 in samples from group M (Table 3, p = 0.04).


Fine specificity of anti-MSP119 antibodies and multiplicity of Plasmodium falciparum merozoite surface protein 1 types in individuals in Nigeria with sub-microscopic infection.

Ngoundou-Landji J, Nwuba RI, Anumudu CI, Odaibo AB, Matondo Maya WD, Awobode HO, Okafor CM, Morenikeji OA, Asinobi A, Nwagwu M, Holder AA, Ntoumi F - Malar. J. (2010)

Distribution and prevalence of MSP1 alleles within sequence block 2 that were identified in the cross sectional survey. The different alleles fall into 3 different sequence families (RO33, MAD20, and K1) within which there are size polymorphisms identified by the size of the PCR amplified fragment (shown in base pairs, bp)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2965716&req=5

Figure 1: Distribution and prevalence of MSP1 alleles within sequence block 2 that were identified in the cross sectional survey. The different alleles fall into 3 different sequence families (RO33, MAD20, and K1) within which there are size polymorphisms identified by the size of the PCR amplified fragment (shown in base pairs, bp)
Mentions: It was of interest to determine whether or not multiplicity of infection (MOI), and the numbers of different MSP1 types affected either the total amount of MSP119-specific antibody or of antibody that competed with the mAbs, and therefore the number of msp1 sequence block 2 types in the samples was used as a marker for MOI and MSP1 polymorphism in each individual. Genotyping of the polymorphic sequence block 2 revealed that RO33 was the predominant allele with 57% of the total, with the K1 and MAD20 allelic families representing 26% and 17%, respectively. Based on size polymorphism, only one RO33 allele was detected whereas the MAD20 and K1 families contained 8 and 13 distinct alleles, respectively (Figure 1). There was no preferential distribution of allelic families between age-groups. The mean minimum MOI based on the number of msp1 genotypes detected for individuals in each age-group is shown in Table 2. The highest MOI was found in the 6 to 15 years age group. Seventy-three of 147 (51%) isolates were found to have more than one P. falciparum genotype. There was no significant influence of age on the proportion of individuals with multiple versus single infections (denoted by M and S, respectively in Table 2) or on MOI. Overall, no correlation between MOI and the mean log titre of anti-MSP119 antibodies was detected. Similarly the MOI was not correlated with inhibition of mAb 12.10 binding. However, comparing the two groups M (multiple infection) and S (single infection), there was a higher prevalence of antibodies that competed with mAb 12.10 in samples from group M (Table 3, p = 0.04).

Bottom Line: The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples.Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10.Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04).

View Article: PubMed Central - HTML - PubMed

Affiliation: 1Université des Sciences et Techniques de Masuku, Franceville, Gabon.

ABSTRACT

Background: The absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP119) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP119 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study.

Methods: Plasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured.

Results: Plasma samples from 85% of individuals contained antibodies that bound to MSP119. The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04).

Conclusions: In the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection.

Show MeSH
Related in: MedlinePlus