Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.
Research School of Chemistry, The Australian National University, Canberra, ACT 2601, Australia.
Cell Rep. 2021 Apr 13;35(2):108996. doi: 10.1016/j.celrep.2021.108996.
Antibodies targeting the NANP/NVDP repeat domain of the Plasmodium falciparum circumsporozoite protein (CSP) can protect against malaria. However, it has also been suggested that the CSP is a decoy that prevents the immune system from mounting responses against other domains of CSP. Here, we show that, following parasite immunization, B cell responses to the CSP are immunodominant over responses to other CSP domains despite the presence of similar numbers of naive B cells able to bind these regions. We find that this immunodominance is driven by avid binding of the CSP to cognate B cells that are able to expand at the expense of B cells with other specificities. We further show that mice immunized with repeat-truncated CSP molecules develop responses to subdominant epitopes and are protected against malaria. These data demonstrate that the CSP functions as a decoy, but truncated CSP molecules may be an approach for malaria vaccination.
针对恶性疟原虫环子孢子蛋白（CSP）的 NANP/NVDP 重复结构域的抗体可以预防疟疾。然而，也有人认为 CSP 是一种诱饵，阻止免疫系统对 CSP 的其他结构域产生反应。在这里，我们发现，尽管存在能够结合这些区域的相同数量的幼稚 B 细胞，但在寄生虫免疫后，B 细胞对 CSP 的反应比对其他 CSP 结构域的反应更具免疫优势。我们发现，这种免疫优势是由 CSP 与能够增殖的同源 B 细胞的强烈结合驱动的，而牺牲了具有其他特异性的 B 细胞。我们进一步表明，用重复截短的 CSP 分子免疫的小鼠会对亚显性表位产生反应，并能预防疟疾。这些数据表明 CSP 作为诱饵发挥作用，但截短的 CSP 分子可能是疟疾疫苗接种的一种方法。
