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dc.contributor.authorSpring, Michele D.
dc.contributor.authorChelimo, Kiprotich
dc.contributor.authorTisch, Daniel J.
dc.contributor.authorSumba, Peter O.
dc.contributor.authorRochford, Rosemary
dc.contributor.authorLong, Carole A.
dc.contributor.authorKazura, James W.
dc.contributor.authorMoormann, Ann M.
dc.date2022-08-11T08:10:44.000
dc.date.accessioned2022-08-23T17:18:25Z
dc.date.available2022-08-23T17:18:25Z
dc.date.issued2010-08-11
dc.date.submitted2011-02-01
dc.identifier.citationInfect Immun. 2010 Oct;78(10):4431-41. Epub 2010 Aug 9. <a href="http://dx.doi.org/10.1128/IAI.00415-10">Link to article on publisher's site</a>
dc.identifier.issn0019-9567 (Linking)
dc.identifier.doi10.1128/IAI.00415-10
dc.identifier.pmid20696832
dc.identifier.urihttp://hdl.handle.net/20.500.14038/47850
dc.description.abstractCross-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-gamma) 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-gamma 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-gamma 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-gamma 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20696832&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1128/IAI.00415-10
dc.subjectAlleles
dc.subjectAnimals
dc.subjectCross-Sectional Studies
dc.subjectGene Expression Regulation
dc.subjectGenotype
dc.subjectHumans
dc.subjectImmunologic Memory
dc.subjectInterferon-gamma
dc.subjectKenya
dc.subjectMalaria, Falciparum
dc.subjectMerozoite Surface Protein 1
dc.subjectPeptide Library
dc.subjectPlasmodium falciparum
dc.subjectSeroepidemiologic Studies
dc.subjectBiostatistics
dc.subjectEpidemiology
dc.subjectHealth Services Research
dc.subjectImmunology and Infectious Disease
dc.titleAllele 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
dc.typeJournal Article
dc.source.journaltitleInfection and immunity
dc.source.volume78
dc.source.issue10
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/qhs_pp/962
dc.identifier.contextkey1755885
html.description.abstract<p>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-gamma) 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-gamma 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-gamma 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-gamma 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.</p>
dc.identifier.submissionpathqhs_pp/962
dc.contributor.departmentDepartment of Pediatrics
dc.contributor.departmentDepartment of Quantitative Health Sciences
dc.source.pages4431-41


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