Limited variation in vaccine candidate Plasmodium falciparum Merozoite Surface Protein-6 over multiple transmission seasons.
Limited variation in vaccine candidate Plasmodium falciparum Merozoite Surface Protein-6 over multiple transmission seasons.
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DOI：
10.1186/1475-2875-9-138
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发表时间：
2010-05-24
期刊：
影响因子：
3
通讯作者：
Rayner JC
中科院分区：
文献类型：
--
作者：
Neal AT;Jordan SJ;Oliveira AL;Hernandez JN;Branch OH;Rayner JC
Plasmodium falciparum Merozoite Surface Protein-6 (PfMSP6) is a component of the complex proteinacious coat that surrounds P. falciparum merozoites. This location, and the presence of anti-PfMSP6 antibodies in P. falciparum-exposed individuals, makes PfMSP6 a potential blood stage vaccine target. However, genetic diversity has proven to be a major hurdle for vaccines targeting other blood stage P. falciparum antigens, and few endemic field studies assessing PfMSP6 gene diversity have been conducted. This study follows PfMSP6 diversity in the Peruvian Amazon from 2003 to 2006 and is the first longitudinal assessment of PfMSP6 sequence dynamics. Parasite DNA was extracted from 506 distinct P. falciparum infections spanning the transmission seasons from 2003 to 2006 as part of the Malaria Immunology and Genetics in the Amazon (MIGIA) cohort study near Iquitos, Peru. PfMSP6 was amplified from each sample using a nested PCR protocol, genotyped for allele class by agarose gel electrophoresis, and sequenced to detect diversity. Allele frequencies were analysed using JMP v.8.0.1.0 and correlated with clinical and epidemiological data collected as part of the MIGIA project. Both PfMSP6 allele classes, K1-like and 3D7-like, were detected at the study site, confirming that both are globally distributed. Allele frequencies varied significantly between transmission seasons, with 3D7-class alleles dominating and K1-class alleles nearly disappearing in 2005 and 2006. There was a significant association between allele class and village location (p-value = 0.0008), but no statistically significant association between allele class and age, sex, or symptom status. No intra-allele class sequence diversity was detected. Both PfMSP6 allele classes are globally distributed, and this study shows that allele frequencies can fluctuate significantly between communities separated by only a few kilometres, and over time in the same community. By contrast, PfMSP6 was highly stable at the sequence level, with no SNPs detected in the 506 samples analysed. This limited diversity supports further investigation of PfMSP6 as a blood stage vaccine candidate, with the clear caveat that any such vaccine must either contain both alleles or generate cross-protective responses that react against both allele classes. Detailed immunoepidemiology studies are needed to establish the viability of these approaches before PfMSP6 advances further down the vaccine development pipeline.
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影响因子：
3.7
作者：
Ogutu BR;Apollo OJ;McKinney D;Okoth W;Siangla J;Dubovsky F;Tucker K;Waitumbi JN;Diggs C;Wittes J;Malkin E;Leach A;Soisson LA;Milman JB;Otieno L;Holland CA;Polhemus M;Remich SA;Ockenhouse CF;Cohen J;Ballou WR;Martin SK;Angov E;Stewart VA;Lyon JA;Heppner DG;Withers MR;MSP-1 Malaria Vaccine Working Group
通讯作者：
MSP-1 Malaria Vaccine Working Group
影响因子：
15.8
作者：
Druilhe P;Spertini F;Soesoe D;Corradin G;Mejia P;Singh S;Audran R;Bouzidi A;Oeuvray C;Roussilhon C
通讯作者：
Roussilhon C
DOI：
10.4269/ajtmh.2006.75.238
发表时间：
2006-08-01
影响因子：
3.3
作者：
Pinedo-Cancino, Viviana;Sheen, Patricia;Gilman, Robert H.
通讯作者：
Gilman, Robert H.
影响因子：
3.1
作者：
Pearce, JA;Triglia, T;Anders, RF
通讯作者：
Anders, RF
DOI：
10.1038/emboj.2009.22
发表时间：
2009-03-18
期刊：
The EMBO journal
影响因子：
--
作者：
Koussis K;Withers-Martinez C;Yeoh S;Child M;Hackett F;Knuepfer E;Juliano L;Woehlbier U;Bujard H;Blackman MJ
通讯作者：
Blackman MJ