Powles Liam, Wilson Kirsty L, Xiang Sue D, Coppel Ross L, Ma Charles, Selomulya Cordelia, Plebanski Magdalena
Department of Chemical Engineering, Monash University, Clayton, VIC 3800, Australia.
Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia.
Vaccines (Basel). 2020 Nov 3;8(4):651. doi: 10.3390/vaccines8040651.
Vaccines against blood-stage malaria often aim to induce antibodies to neutralize parasite entry into red blood cells, interferon gamma (IFNγ) produced by T helper 1 (Th1) CD4+ T cells or interleukin 4 (IL-4) produced by T helper 2 (Th2) cells to provide B cell help. One vaccine delivery method for suitable putative malaria protein antigens is the use of nanoparticles as vaccine carriers. It has been previously shown that antigen conjugated to inorganic nanoparticles in the viral-particle size range (~40-60 nm) can induce protective antibodies and T cells against malaria antigens in a rodent malaria challenge model. Herein, it is shown that biodegradable pullulan-coated iron oxide nanoparticles (pIONPs) can be synthesized in this same size range. The pIONPs are non-toxic and do not induce conventional pro-inflammatory cytokines in vitro and in vivo. We show that murine blood-stage antigen MSP4/5 from could be chemically conjugated to pIONPs and the use of these conjugates as immunogens led to the induction of both specific antibodies and IFNγ CD4+ T cells reactive to MSP4/5 in mice, comparable to responses to MSP4/5 mixed with classical adjuvants (e.g., CpG or Alum) that preferentially induce Th1 or Th2 cells individually. These results suggest that biodegradable pIONPs warrant further exploration as carriers for developing blood-stage malaria vaccines.
针对血液期疟疾的疫苗通常旨在诱导抗体以中和寄生虫进入红细胞，诱导辅助性T细胞1（Th1）CD4 + T细胞产生的干扰素γ（IFNγ）或辅助性T细胞2（Th2）细胞产生的白细胞介素4（IL-4），从而为B细胞提供帮助。一种适用于假定的疟疾蛋白抗原的疫苗递送方法是使用纳米颗粒作为疫苗载体。先前已表明，与病毒颗粒大小范围（约40 - 60纳米）的无机纳米颗粒偶联的抗原可在啮齿动物疟疾攻击模型中诱导针对疟疾抗原的保护性抗体和T细胞。在此表明，可在相同大小范围内合成可生物降解的支链淀粉包被的氧化铁纳米颗粒（pIONP）。pIONP无毒，在体外和体内均不诱导传统的促炎细胞因子。我们表明，来自[具体来源未给出]的鼠血液期抗原MSP4/5可化学偶联到pIONP上，并且使用这些偶联物作为免疫原可在小鼠中诱导对MSP4/5有反应的特异性抗体和IFNγ CD4 + T细胞，这与对分别优先诱导Th1或Th2细胞的经典佐剂（例如CpG或明矾）混合的MSP4/5的反应相当。这些结果表明，可生物降解的pIONP作为开发血液期疟疾疫苗的载体值得进一步探索。
