Antibodies from malaria-exposed Malians generally interact additively or synergistically with human vaccine-induced RH5 antibodies.

Antibodies from malaria-exposed Malians generally interact additively or synergistically with human vaccine-induced RH5 antibodies.
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DOI:
10.1016/j.xcrm.2021.100326
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发表时间:
2021-07-20
期刊:
Cell reports. Medicine
影响因子:
--
通讯作者:
Miura K
Miura K
中科院分区:
其他
文献类型:
--
作者:
Willcox AC;Huber AS;Diouf A;Barrett JR;Silk SE;Pulido D;King LDW;Alanine DGW;Minassian AM;Diakite M;Draper SJ;Long CA;Miura K

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网织红细胞结合蛋白同源物5(RH5)是一种主要的恶性疟原虫血液阶段疫苗候选者。另一种可能的候选物,顶端膜抗原1(AMA1),在疟疾流行人群中无效,可能是由于预先存在的抗疟疾抗体干扰了疫苗诱导的AMA1抗体的活性,通过体外生长抑制试验(GIA)判断。为了确定预先存在的抗体如何与疫苗诱导的RH5抗体相互作用,我们从疟疾暴露的马里人和未感染疟疾的RH5疫苗接种者中纯化总的和RH5特异性免疫球蛋白G(IgG)。免疫诱导的RH5抗体滴度远低于疫苗接种诱导的抗体滴度,并且RH5特异性IgG显示两个群体之间结合位点的差异。在GIA中,马里多克隆IgG显示与RH5人单克隆抗体的相加或协同相互作用,以及与疫苗诱导的多克隆RH5 IgG的总体相加相互作用。这些结果表明,与AMA1抗体相反,预先存在的抗体将与疫苗诱导的RH5抗体有利地相互作用。这项研究支持在疟疾流行地区进行RH5疫苗试验。由感染诱导的RH5 IgG滴度低于由RH5疫苗接种诱导的那些。感染诱导的和疫苗诱导的RH5 IgG具有不同的特异性和亲合力感染诱导的和疫苗诱导的RH5 IgG与RH5 mAb的相互作用不同。联合收割机抗体来自疟疾暴露的马里人和接受网织红细胞结合蛋白同源物5(RH5)疫苗的志愿者。在恶性疟原虫生长抑制测定中,感染诱导的IgG通常不降低疫苗诱导的IgG的中和活性。这些结果表明,RH5疫苗将在疟疾流行人群中诱导有效的抗体。
Reticulocyte-binding protein homolog 5 (RH5) is a leading Plasmodium falciparum blood-stage vaccine candidate. Another possible candidate, apical membrane antigen 1 (AMA1), was not efficacious in malaria-endemic populations, likely due to pre-existing antimalarial antibodies that interfered with the activity of vaccine-induced AMA1 antibodies, as judged by in vitro growth inhibition assay (GIA). To determine how pre-existing antibodies interact with vaccine-induced RH5 antibodies, we purify total and RH5-specific immunoglobulin Gs (IgGs) from malaria-exposed Malians and malaria-naive RH5 vaccinees. Infection-induced RH5 antibody titers are much lower than those induced by vaccination, and RH5-specific IgGs show differences in the binding site between the two populations. In GIA, Malian polyclonal IgGs show additive or synergistic interactions with RH5 human monoclonal antibodies and overall additive interactions with vaccine-induced polyclonal RH5 IgGs. These results suggest that pre-existing antibodies will interact favorably with vaccine-induced RH5 antibodies, in contrast to AMA1 antibodies. This study supports RH5 vaccine trials in malaria-endemic regions. RH5 IgG titers induced by infection are lower than those induced by RH5 vaccination Infection- and vaccine-induced RH5 IgGs have different specificity and avidity Infection- and vaccine-induced RH5 IgGs interact differently with RH5 mAbs Infection-induced IgGs generally do not reduce the activity of vaccine-induced IgGs Willcox et al. combine antibodies from malaria-exposed Malians and volunteers who received a reticulocyte-binding protein homolog 5 (RH5) vaccine. In P. falciparum growth inhibition assays, infection-induced IgGs generally do not reduce the neutralizing activity of vaccine-induced IgGs. These results suggest that RH5 vaccines will induce effective antibodies in malaria-endemic populations.
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期刊: Journal of immunology (Baltimore, Md. : 1950)
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