Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom.
Cell Rep Med. 2021 Jun 21;2(7):100326. doi: 10.1016/j.xcrm.2021.100326. eCollection 2021 Jul 20.
Reticulocyte-binding protein homolog 5 (RH5) is a leading 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 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.
红细胞结合蛋白同源物 5（RH5）是一种领先的血期疫苗候选物。另一种可能的候选物，顶端膜抗原 1（AMA1），在疟疾流行地区没有效果，这可能是由于预先存在的抗疟抗体干扰了疫苗诱导的 AMA1 抗体的活性，这可以通过生长抑制试验（GIA）来判断。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 RH5 疫苗接种的疟疾未感染者中纯化总免疫球蛋白 G（IgG）和 RH5 特异性 IgG。感染诱导的 RH5 抗体滴度低于疫苗接种诱导的 RH5 抗体滴度，并且 RH5 特异性 IgG 在这两个人群之间的结合位点存在差异。在 GIA 中，马里多克隆 IgG 与 RH5 人单克隆抗体表现出相加或协同相互作用，与疫苗诱导的多克隆 RH5 IgG 总体上表现出相加相互作用。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。
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