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dc.contributor.authorDent, Arlene E.
dc.contributor.authorMoormann, Ann M.
dc.contributor.authorYohn, Christopher T.
dc.contributor.authorKimmel, Rhonda J.
dc.contributor.authorSumba, Peter Odada
dc.contributor.authorVulule, John
dc.contributor.authorLong, Carole A.
dc.contributor.authorNarum, David L.
dc.contributor.authorCrabb, Brendan S.
dc.contributor.authorKazura, James W.
dc.contributor.authorTisch, Daniel J.
dc.date2022-08-11T08:10:33.000
dc.date.accessioned2022-08-23T17:12:48Z
dc.date.available2022-08-23T17:12:48Z
dc.date.issued2012-08-21
dc.date.submitted2012-10-23
dc.identifier.citationMalar J. 2012 Aug 21;11(1):287. <a href="http://dx.doi.org/10.1186/1475-2875-11-287" target="_blank">Link to article on publisher's site</a>
dc.identifier.issn1475-2875 (Linking)
dc.identifier.doi10.1186/1475-2875-11-287
dc.identifier.pmid22909378
dc.identifier.urihttp://hdl.handle.net/20.500.14038/46582
dc.description.abstractBACKGROUND: The 19 kDa C-terminal region of Plasmodium falciparum Merozoite Surface Protein-1 is a known target of naturally acquired humoral immunity and a malaria vaccine candidate. MSP- 119 has four predominant haplotypes resulting in amino acid changes labelled EKNG, QKNG, QTSR and ETSR. IgG antibodies directed against all four variants have been detected, but it is not known if these variant specific antibodies are associated with haplotype-specific protection from infection. METHODS: Blood samples from 201 healthy Kenyan adults and children who participated in a 12-week treatment time-to-infection study were evaluated. Venous blood drawn at baseline (week 0) was examined for functional and serologic antibodies to MSP-119 and MSP-142 variants. MSP-119 haplotypes were detected by a multiplex PCR assay at baseline and weekly throughout the study. Generalized linear models controlling for age, baseline MSP-119 haplotype and parasite density were used to determine the relationship between infecting P. falciparum MSP-119 haplotype and variant-specific antibodies. RESULTS: A total of 964 infections resulting in 1,533 MSP-119 haplotypes detected were examined. The most common haplotypes were EKNG and QKNG, followed by ETSR and QTSR. Children had higher parasite densities, greater complexity of infection (>1 haplotype), and more frequent changes in haplotypes over time compared to adults. Infecting MSP-119 haplotype at baseline (week 0) had no influence on haplotypes detected over the subsequent 11 weeks among children or adults. Children but not adults with MSP-119 and some MSP-142 variant antibodies detected by serology at baseline had delayed time-to-infection. There was no significant association of variant-specific serology or functional antibodies at baseline with infecting haplotype at baseline or during 11 weeks of follow up among children or adults. CONCLUSIONS: Variant transcending IgG antibodies to MSP-119 are associated with protection from infection in children, but not adults. These data suggest that inclusion of more than one MSP-119 variant may not be required in a malaria blood stage vaccine.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22909378&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
dc.subjectMalaria, Falciparum
dc.subjectMerozoite Surface Protein 1
dc.subjectAntigens, Protozoan
dc.subjectEpidemiology
dc.subjectHealth Services Research
dc.subjectImmunology and Infectious Disease
dc.subjectParasitic Diseases
dc.titleBroadly reactive antibodies specific for Plasmodium falciparum MSP-119 are associated with the protection of naturally exposed children against infection
dc.typeJournal Article
dc.source.journaltitleMalaria journal
dc.source.volume11
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2048&amp;context=qhs_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/qhs_pp/1048
dc.identifier.contextkey3418844
refterms.dateFOA2022-08-23T17:12:48Z
html.description.abstract<p>BACKGROUND: The 19 kDa C-terminal region of Plasmodium falciparum Merozoite Surface Protein-1 is a known target of naturally acquired humoral immunity and a malaria vaccine candidate. MSP- 119 has four predominant haplotypes resulting in amino acid changes labelled EKNG, QKNG, QTSR and ETSR. IgG antibodies directed against all four variants have been detected, but it is not known if these variant specific antibodies are associated with haplotype-specific protection from infection.</p> <p>METHODS: Blood samples from 201 healthy Kenyan adults and children who participated in a 12-week treatment time-to-infection study were evaluated. Venous blood drawn at baseline (week 0) was examined for functional and serologic antibodies to MSP-119 and MSP-142 variants. MSP-119 haplotypes were detected by a multiplex PCR assay at baseline and weekly throughout the study. Generalized linear models controlling for age, baseline MSP-119 haplotype and parasite density were used to determine the relationship between infecting P. falciparum MSP-119 haplotype and variant-specific antibodies.</p> <p>RESULTS: A total of 964 infections resulting in 1,533 MSP-119 haplotypes detected were examined. The most common haplotypes were EKNG and QKNG, followed by ETSR and QTSR. Children had higher parasite densities, greater complexity of infection (>1 haplotype), and more frequent changes in haplotypes over time compared to adults. Infecting MSP-119 haplotype at baseline (week 0) had no influence on haplotypes detected over the subsequent 11 weeks among children or adults. Children but not adults with MSP-119 and some MSP-142 variant antibodies detected by serology at baseline had delayed time-to-infection. There was no significant association of variant-specific serology or functional antibodies at baseline with infecting haplotype at baseline or during 11 weeks of follow up among children or adults.</p> <p>CONCLUSIONS: Variant transcending IgG antibodies to MSP-119 are associated with protection from infection in children, but not adults. These data suggest that inclusion of more than one MSP-119 variant may not be required in a malaria blood stage vaccine.</p>
dc.identifier.submissionpathqhs_pp/1048
dc.contributor.departmentDepartment of Pediatrics
dc.contributor.departmentDepartment of Quantitative Health Sciences
dc.source.pages287


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