Fine specificity of anti-MSP119 antibodies and multiplicity of Plasmodium falciparum Merozoite Surface Protein 1 types in individuals in Nigeria with sub-microscopic infection

Abstract

BackgroundThe 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.MethodsPlasma 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.ResultsPlasma 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).ConclusionsIn 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.

The Impact of HIV and Plasmodium falciparum Genetic Diversity on Anaemia in HIV-patients Attending Care and Treatment Centre at Baptist Hospital Mutengene

“…The identification of more than one genotype of MSP-1 (block 2) and MSP-2 (block 3) genes among the samples portrayed the genetic diversity of parasite genotypes that exist among patients infected with P. falciparum. This is consistent with other studies where allelic variants of MSP-1 and MSP-2 have been reported in other countries [13,28,39,[40][41][42] though not specifically among HIV-patients. The genetic diversity of P. falciparum populations and the complexity of infection have been reported to vary according to the intensity of transmission in different geographical areas with the existence of size polymorphism as identified by the size of the PCR amplified fragment [10][11][12][13][14].…”

Global phylogeography of the avian malaria pathogen Plasmodium relictum based on MSP1 allelic diversity

“…Our discovery of multiple independent loci of avian Plasmodium parasites provides insight into species limits, levels of differentiation, and gene‐flow among parasite populations. Allelic variation at a gene locus such as MSP1, which is known to be linked to immunity (Ngoundou‐Landji et al ) as well as being a protein involved in the invasion of the red blood cells (Kadekoppala and Holder , Wright and Rayner ), allows us to study how this variation might be linked to differences in host–parasite interactions. Such studies are crucial to understanding the evolution of local patterns of virulence and host resistance.…”

“…The MSP1 gene encodes a 190 kDa protein that during erythrocytic schizogony (merogony) is anchored to the parasite's cell membrane (Gerold et al ). Antibodies to the peptide are frequent in human populations with high malaria prevalence and can be associated with resistance to the parasite (Hui and Hashimoto , Ngoundou‐Landji et al ). Because MSP1 is one of the major proteins that coats the parasite during its extracellular state and is associated with the initial attachment to host red blood cells, it is likely to interact with the immune system and parasite evasion mechanism of the host.…”

Diversity Covering AMA1-MSP1 19 Fusion Proteins as Malaria Vaccines

“…Including both variants of MSP1 19 in the vaccine does not lead to an improved immunogenicity profile with respect to coverage. However, if the DiCo principle applies, use of a combination of two or more engineered MSP1 19 modules may still be beneficial, as the combination could target the immune response to epitopes of choice, enabling the fine specificity that is deemed necessary to make an MSP1 19 -based vaccine work (47)(48)(49).…”