Antibody response of a particle-inducing, liposome vaccine adjuvant admixed with a Pfs230 fragment
Antibody response of a particle-inducing, liposome vaccine adjuvant admixed with a Pfs230 fragment
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DOI：
10.1038/s41541-020-0173-x
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发表时间：
2020-03-18
期刊：
影响因子：
9.2
通讯作者：
Lovell, Jonathan F.
中科院分区：
文献类型：
--
作者：
Huang, Wei-Chiao;Deng, Bingbing;Lovell, Jonathan F.
Pfs 230是一种疟疾传播阻断抗原候选物，表达于恶性疟原虫配子体表面。重组的His标记的Pfs 230片段（Pfs 230 C1;氨基酸443-731）在与含有钴卟啉磷脂（CoPoP）的脂质体孵育后形成血清稳定的颗粒。在小鼠中，与佐剂明矾、Montanide ISA 720或CoPoP脂质体（也含有合成的单磷酰脂质A; PHAD）混合的Pfs 230 C1免疫导致IgG抗体的激发，但仅用CoPoP/PHAD或ISA 720诱导的那些强烈降低寄生虫传播。用缺乏钴（其不诱导颗粒形成）或明矾的相同脂质体辅助的微克Pfs 230 C1免疫比用具有CoPoP/PHAD的纳克Pfs 230 C1免疫有效性低。CoPoP/PHAD和ISA 720佐剂诱导的抗体具有相似的Pfs 230 C1亲合力，但比Alum更高的IgG 2与IgG 1比率，这可能有助于增强功能活性。与先前使用另一种传播阻断抗原（Pfs 25）的工作不同，发现Pfs 230 C1被抗原呈递细胞有效摄取而不形成颗粒。在用CoPoP/PHAD免疫后，抗Pfs 230 C1 IgG应答在小鼠中持续250天，抗体亲合力和升高的IgG 2与IgG 1比率也是如此。用与CoPoP/PHAD混合的20 μ g Pfs 230 C1免疫兔子，引起抑制寄生虫传播的抗体。总之，这些结果表明，含有CoPoP和PHAD的脂质体是重组疟疾传播阻断抗原的有效疫苗佐剂平台。
Pfs230 is a malaria transmission-blocking antigen candidate, expressed on the surface of Plasmodium falciparum gametocytes. A recombinant, his-tagged Pfs230 fragment (Pfs230C1; amino acids 443-731) formed serum-stable particles upon incubation with liposomes containing cobalt-porphyrin-phospholipid (CoPoP). In mice, immunization with Pfs230C1, admixed with the adjuvants Alum, Montanide ISA720 or CoPoP liposomes (also containing synthetic monophosphoryl lipid A; PHAD), resulted in elicitation of IgG antibodies, but only those induced with CoPoP/PHAD or ISA720 strongly reduced parasite transmission. Immunization with micrograms of Pfs230C1 adjuvanted with identical liposomes lacking cobalt (that did not induce particle formation) or Alum was less effective than immunization with nanograms of Pfs230C1 with CoPoP/PHAD. CoPoP/PHAD and ISA720 adjuvants induced antibodies with similar Pfs230C1 avidity but higher IgG2-to-IgG1 ratios than Alum, which likely contributed to enhanced functional activity. Unlike prior work with another transmission-blocking antigen (Pfs25), Pfs230C1 was found to be effectively taken up by antigen-presenting cells without particle formation. The anti-Pfs230C1 IgG response was durable in mice for 250 days following immunization with CoPoP/PHAD, as were antibody avidity and elevated IgG2-to-IgG1 ratios. Immunization of rabbits with 20 mu g Pfs230C1 admixed with CoPoP/PHAD elicited antibodies that inhibited parasite transmission. Taken together, these results show that liposomes containing CoPoP and PHAD are an effective vaccine adjuvant platform for recombinant malaria transmission blocking antigens.