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.

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.
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具有自然获得性疟疾免疫力的肯尼亚成年人对恶性疟原虫裂殖子表面蛋白 1 羧基末端区域的 γ 干扰素反应的等位基因特异性。

DOI:
10.1128/iai.00415-10
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发表时间:
2010
影响因子:
3.1
通讯作者:
Moormann,AnnM
Moormann,AnnM
中科院分区:
医学2区
文献类型:
--
作者:
Spring,MicheleD;Chelimo,Kiprotich;Tisch,DanielJ;Sumba,PeterOdada;Rochford,Rosemary;Long,CaroleA;Kazura,JamesW;Moormann,AnnM

文献摘要

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Cross-sectional seroepidemiological studies of populations naturally exposed toPlasmodium falciparumsuggest 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 (MSP142), which includes the 19-kDa (MSP119) and 33-kDa (MSP133) fragments containing the major B- and T-cell epitopes, respectively. To evaluate T-cell responses to the MSP133fragment, two libraries of overlapping 18-mer peptides from the 3D7 and FVO MSP133regions were used to screen a cohort of asymptomatic Kenyan adults. Gamma interferon (IFN-γ) 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-γ responses to single MSP133peptides 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-γ ELISPOT responses to recombinant MSP142were more prevalent, more frequently elicited by the 3D7 as opposed to the FVO allele, and more stable over time. The prevailing MSP133genotype infection was 3D7, with few mixed infections and no sole FVO infections. This study demonstrates that immunity against MSP133after cumulative natural infections consists of low-magnitude and difficult-to-detect IFN-γ 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.