Abstract:
:Individuals living in areas where malaria is endemic are repeatedly exposed to many different malaria parasite antigens. Studies on naturally acquired antibody-mediated immunity to clinical malaria have largely focused on the presence of responses to individual antigens and their associations with decreased morbidity. We hypothesized that the breadth (number of important targets to which antibodies were made) and magnitude (antibody level measured in a random serum sample) of the antibody response were important predictors of protection from clinical malaria. We analyzed naturally acquired antibodies to five leading Plasmodium falciparum merozoite-stage vaccine candidate antigens, and schizont extract, in Kenyan children monitored for uncomplicated malaria for 6 months (n = 119). Serum antibody levels to apical membrane antigen 1 (AMA1) and merozoite surface protein antigens (MSP-1 block 2, MSP-2, and MSP-3) were inversely related to the probability of developing malaria, but levels to MSP-1(19) and erythrocyte binding antigen (EBA-175) were not. The risk of malaria was also inversely associated with increasing breadth of antibody specificities, with none of the children who simultaneously had high antibody levels to five or more antigens experiencing a clinical episode (17/119; 15%; P = 0.0006). Particular combinations of antibodies (AMA1, MSP-2, and MSP-3) were more strongly predictive of protection than others. The results were validated in a larger, separate case-control study whose end point was malaria severe enough to warrant hospital admission (n = 387). These findings suggest that under natural exposure, immunity to malaria may result from high titers antibodies to multiple antigenic targets and support the idea of testing combination blood-stage vaccines optimized to induce similar antibody profiles.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Osier FH,Fegan G,Polley SD,Murungi L,Verra F,Tetteh KK,Lowe B,Mwangi T,Bull PC,Thomas AW,Cavanagh DR,McBride JS,Lanar DE,Mackinnon MJ,Conway DJ,Marsh Kdoi
10.1128/IAI.01585-07subject
Has Abstractpub_date
2008-05-01 00:00:00pages
2240-8issue
5eissn
0019-9567issn
1098-5522pii
IAI.01585-07journal_volume
76pub_type
杂志文章abstract::Human serum at low concentrations inhibits the growth of Cryptococcus neoformans in vitro. Fractionation of serum yielded a purified inhibitory protein with a molecular mass of approximately 81.8 kDa, a pI of approximately 6.2, and an amino acid sequence that matched that of human transferrin. The inhibitory activity ...
journal_title:Infection and immunity
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doi:10.1128/iai.68.6.3787-3791.2000
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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doi:10.1128/IAI.63.10.3846-3850.1995
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doi:10.1128/IAI.66.2.703-709.1998
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.71.10.5690-5699.2003
更新日期:2003-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.5.1520-1527.1994
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.41.1.257-263.1983
更新日期:1983-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.45.3.768-774.1984
更新日期:1984-09-01 00:00:00
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