Comparison of biological activity of human anti-apical membrane antigen-1 antibodies induced by natural infection and vaccination.
Comparison of biological activity of human anti-apical membrane antigen-1 antibodies induced by natural infection and vaccination.
复制标题
自然感染和疫苗接种诱导的人类抗膜抗原-1抗体的生物学活性的比较。
DOI：
10.4049/jimmunol.181.12.8776
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Long CA
中科院分区：
文献类型：
--
作者：
Miura K;Zhou H;Moretz SE;Diouf A;Thera MA;Dolo A;Doumbo O;Malkin E;Diemert D;Miller LH;Mullen GE;Long CA
疫苗是降低全球疟疾发病率和死亡率的重要潜在手段。在美国对恶性疟原虫顶膜抗原1(AMA1)进行的临床试验表明，该疫苗诱导了体外寄生虫生长抑制试验(GIA)判断的生物活性抗体。然而，同样的疫苗在马里成年人身上并没有增加生物活性，尽管它提高了ELISA效价。由于GIA已被用于评估血液期疟疾候选疫苗诱导的抗体的生物活性，我们在这项研究中探索了这一差异。我们从美国接种疫苗的人和生活在马里疟疾流行地区的未接种疫苗的人身上亲和纯化了AMA1特异性抗体，并进行了ELISA和GIA。当ELISA效价正常化时，接种疫苗(美国)和自然感染(马里)诱导的AMA1特异性抗体在GIA中具有类似的生物学活性。然而，一小部分不与AMA1蛋白结合的马里人免疫球蛋白(马里-非AMA1免疫球蛋白)降低了来自美国疫苗接种者的AMA1抗体的生物活性；相反，美国-非AMA1免疫球蛋白没有表现出生物活性降低。进一步调查表明，减少是由于马里非AMA1免疫球蛋白中的疟疾特效免疫球蛋白。美国和马里的AMA1特异性抗体都显示出类似的生物活性，这一事实支持了基于AMA1的疫苗的进一步开发。然而，其他疟疾特异性免疫球蛋白降低了AMA1特异性抗体的生物活性，这可能解释了在马里成人中接种AMA1疫苗对抗体生长抑制活性的有限影响，并可能使开发血液期疟疾疫苗的努力复杂化。
Vaccines represent a significant potential means of decreasing global morbidity and mortality due to malaria. Clinical trials in the U.S. with Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) showed that the vaccine induced biologically active antibodies judged by an in vitro parasite Growth Inhibition Assay (GIA). However, the same vaccine in Malian adults did not increase biological activity although it elevated ELISA titers. As GIA has been used to evaluate the biological activity of antibodies induced by blood-stage malarial vaccine candidates, we explored this discrepancy in this study. We affinity purified AMA1-specific antibodies from both US vaccinees and from non-vaccinated individuals living in a malaria-endemic area of Mali, and performed ELISA and GIA. Both AMA1-specifc antibodies induced by vaccination (US) and by natural infection (Mali) have comparable biological activity in GIA when the ELISA titer is normalized. However, a fraction of Malians’ IgG which did not bind to AMA1 protein (Mali-non-AMA1 IgG) reduced the biological activity of the AMA1 antibodies from US vaccinees; in contrast, US-non-AMA1 IgGs did not show a reduction of the biological activity. Further investigation revealed that the reduction was due to malaria-specific IgGs in the Mali-non-AMA1 IgGs. The fact that both US- and Mali-AMA1-specific antibodies showed comparable biological activity supports further development of AMA1-based vaccines. However, the reduction of biological activity of AMA1-specific antibody by other malaria-specific IgGs likely explains the limited effect on growth-inhibitory activity of antibodies induced by AMA1 vaccination in Malian adults and may complicate efforts to develop a blood-stage malaria vaccine.
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影响因子：
3.7
作者：
Mullen GE;Ellis RD;Miura K;Malkin E;Nolan C;Hay M;Fay MP;Saul A;Zhu D;Rausch K;Moretz S;Zhou H;Long CA;Miller LH;Treanor J
通讯作者：
Treanor J
DOI：
10.1084/jem.186.10.1689
发表时间：
1997-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guevara Patiño JA;Holder AA;McBride JS;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
3.1
作者：
Nebie, Issa;Diarra, Amidou;Sirima, Sodiomon B.
通讯作者：
Sirima, Sodiomon B.
影响因子：
3.1
作者：
Giersing, B;Miura, K;Singh, S
通讯作者：
Singh, S
影响因子：
1.5
作者：
NARUM, DL;THOMAS, AW
通讯作者：
THOMAS, AW