Clinical Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Switzerland.
J Infect Dis. 2018 Apr 23;217(10):1569-1578. doi: 10.1093/infdis/jiy080.
The assessment of antibody responses after immunization with radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (Sanaria PfSPZ Vaccine) has focused on IgG isotype antibodies. Here, we aimed to investigate if P. falciparum sporozoite binding and invasion-inhibitory IgM antibodies are induced following immunization of malaria-preexposed volunteers with PfSPZ Vaccine.
Using serum from volunteers immunized with PfSPZ, we measured vaccine-induced IgG and IgM antibodies to P. falciparum circumsporozoite protein (PfCSP) via ELISA. Function of this serum as well as IgM antibody fractions was measured via in vitro in an inhibition of sporozoite invasion assay. These IgM antibody fractions were also measured for binding to sporozoites by immunofluorescence assay and complement fixation on whole sporozoites.
We found that in addition to anti-PfCSP IgG, malaria-preexposed volunteers developed anti-PfCSP IgM antibodies after immunization with PfSPZ Vaccine and that these IgM antibodies inhibited P. falciparum sporozoite invasion of hepatocytes in vitro. These IgM plasma fractions also fixed complement to whole P. falciparum sporozoites.
This is the first finding that PfCSP and P. falciparum sporozoite-binding IgM antibodies are induced following immunization of PfSPZ Vaccine in malaria-preexposed individuals and that IgM antibodies can inhibit P. falciparum sporozoite invasion into hepatocytes in vitro and fix complement on sporozoites. These findings indicate that the immunological assessment of PfSPZ Vaccine-induced antibody responses could be more sensitive if they include parasite-specific IgM in addition to IgG antibodies.
NCT02132299.
评估经辐射减毒、无菌、纯化、冷冻保存的恶性疟原虫孢子（Sanaria PfSPZ 疫苗）免疫后的抗体反应主要集中在 IgG 同种型抗体上。在这里，我们旨在研究疟疾前期暴露的志愿者用 PfSPZ 疫苗免疫后是否会产生疟原虫孢子结合和入侵抑制性 IgM 抗体。
使用来自 PfSPZ 免疫志愿者的血清，我们通过 ELISA 测量疫苗诱导的针对恶性疟原虫环子孢子蛋白（PfCSP）的 IgG 和 IgM 抗体。通过体外抑制孢子入侵试验测量这种血清以及 IgM 抗体片段的功能。还通过免疫荧光法和整个孢子上的补体固定来测量这些 IgM 抗体片段与孢子的结合。
我们发现，除了抗 PfCSP IgG 之外，PfSPZ 疫苗免疫后，疟疾前期暴露的志愿者还产生了抗 PfCSP IgM 抗体，并且这些 IgM 抗体在体外抑制了恶性疟原虫孢子对肝细胞的入侵。这些 IgM 血浆片段还固定了整个恶性疟原虫孢子上的补体。
这是首次发现 PfSPZ 疫苗免疫疟疾前期个体后会诱导 PfCSP 和恶性疟原虫孢子结合的 IgM 抗体，并且 IgM 抗体可以抑制恶性疟原虫孢子在体外入侵肝细胞并固定在孢子上的补体。这些发现表明，如果免疫评估除了 IgG 抗体之外还包括寄生虫特异性 IgM，那么对 PfSPZ 疫苗诱导的抗体反应的免疫评估可能会更敏感。
NCT02132299。
