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Allele specificity of gamma interferon responses to the carboxyl-terminal region of Plasmodium falciparum merozoite surface protein 1 by Kenyan adults with naturally acquired immunity to malaria.

ABSTRACT: Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from malaria and circulating antibodies to the carboxyl terminus of merozoite surface protein 1 (MSP1). Questions remain regarding the significance of cell-mediated immunity to MSP1 in conferring protection and inducing immunologic memory. Vaccine constructs have been based on the 42-kDa recombinant MSP1 protein (MSP1(42)), which includes the 19-kDa (MSP1(19)) and 33-kDa (MSP1(33)) fragments containing the major B- and T-cell epitopes, respectively. To evaluate T-cell responses to the MSP1(33) fragment, two libraries of overlapping 18-mer peptides from the 3D7 and FVO MSP1(33) regions were used to screen a cohort of asymptomatic Kenyan adults. Gamma interferon (IFN-?) measured by enzyme-linked immunospot assay (ELISPOT) at multiple time points assessed the magnitude and stability of these responses. The percentage of individuals with IFN-? responses to single MSP1(33) peptides ranged from nil to 24%, were clustered among a subset of peptides, and were not consistently recalled over time. In comparison to peptide responses, IFN-? ELISPOT responses to recombinant MSP1(42) were more prevalent, more frequently elicited by the 3D7 as opposed to the FVO allele, and more stable over time. The prevailing MSP1(33) genotype infection was 3D7, with few mixed infections and no sole FVO infections. This study demonstrates that immunity against MSP1(33) after cumulative natural infections consists of low-magnitude and difficult-to-detect IFN-? responses. Although immunity against MSP1 alone will not confer protection against malaria, demonstrating a relative and sustained increase in T-cell immunity to MSP1 after vaccination would be a reasonable measurement of vaccine responsiveness.

SUBMITTER: Spring MD

PROVIDER: S-EPMC2950343 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Allele specificity of gamma interferon responses to the carboxyl-terminal region of Plasmodium falciparum merozoite surface protein 1 by Kenyan adults with naturally acquired immunity to malaria.

Spring Michele D MD Chelimo Kiprotich K Tisch Daniel J DJ Sumba Peter Odada PO Rochford Rosemary R Long Carole A CA Kazura James W JW Moormann Ann M AM

Infection and immunity 20100809 10

Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from malaria and circulating antibodies to the carboxyl terminus of merozoite surface protein 1 (MSP1). Questions remain regarding the significance of cell-mediated immunity to MSP1 in conferring protection and inducing immunologic memory. Vaccine constructs have been based on the 42-kDa recombinant MSP1 protein (MSP1(42)), which includes the 19-kDa (MSP ...[more]

PMID: 20696832

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Project description:Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.

Dataset Information

Allele specificity of gamma interferon responses to the carboxyl-terminal region of Plasmodium falciparum merozoite surface protein 1 by Kenyan adults with naturally acquired immunity to malaria.

Publications

Allele specificity of gamma interferon responses to the carboxyl-terminal region of Plasmodium falciparum merozoite surface protein 1 by Kenyan adults with naturally acquired immunity to malaria.

Similar Datasets

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