Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.
Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.
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DOI：
10.1371/journal.pone.0015391
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发表时间：
2010-11-03
期刊：
影响因子：
3.7
通讯作者：
Remarque EJ
中科院分区：
文献类型：
--
作者：
Kusi KA;Faber BW;Riasat V;Thomas AW;Kocken CH;Remarque EJ
人们对多等位基因疫苗越来越感兴趣，以克服针对顶膜抗原 1 (AMA1) 等多态性疫苗靶点的毒株特异性。这些已被证明可以在体外诱导广泛的抑制性抗体，并为设计具有相似免疫作用的三种多样性覆盖（DiCo）蛋白奠定了基础。产生的抗体针对疫苗等位基因之间共享的表位，理论上，增加 AMA1 等位基因的数量预计会扩大抗体反应。然而，平台效应可能会限制实现最广泛特异性所需的等位基因数量。此外，生产成本和疫苗配制过程将限制成分等位基因的数量。在本文中，我们比较了包含七种（三种 DiCos 和四种天然 AMA1 等位基因）和三种（DiCo 混合）抗原的多等位基因疫苗引起的兔抗体反应，以获得更广泛的特异性。我们还研究了三种佐剂平台对抗原特异性和抗体功能的影响。我们的数据证实，使用所有三种佐剂中的 DiCo 混合物进行免疫后，反应范围扩大。使用 CoVaccine HT™ 或 Montanide ISA 51 可以引发更高的抗体滴度，从而对六种培养适应的恶性疟原虫菌株中的五种产生类似的体外抑制作用 (65-82%)。引发的抗体的抗原结合特异性也相似并且独立于所使用的佐剂或疫苗成分等位基因的数量。因此，四种额外抗原和佐剂在特异性拓宽方面都没有任何可观察到的益处，尽管佐剂的选择影响绝对抗体水平，从而影响寄生虫抑制的程度。我们的数据证实了多等位基因 PfAMA1 制剂的可行性和潜力，并强调了基于 AMA1 的疫苗需要具有改进的抗体增强特性的佐剂。
There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1). These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo) proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles) and three (DiCo mix) antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65–82%) of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.
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影响因子：
6.7
作者：
Collins, Christine R.;Withers-Martinez, Chrislaine;Hackett, Fiona;Blackman, Michael J.
通讯作者：
Blackman, Michael J.
DOI：
10.1073/pnas.0701464104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Dutta, Sheetij;Lee, Seung Yeon;Lanar, David E.
通讯作者：
Lanar, David E.
影响因子：
5.2
作者：
Aide, Pedro;Bassat, Quique;Alonso, Pedro L.
通讯作者：
Alonso, Pedro L.
影响因子：
3.1
作者：
Crewther, PE;Matthew, MLSM;Anders, RF
通讯作者：
Anders, RF
DOI：
10.4269/ajtmh.1994.51.711
发表时间：
1994-12-01
影响因子：
3.3
作者：
COLLINS, WE;PYE, D;ANDERS, RF
通讯作者：
ANDERS, RF