抗原
免疫原性
佐剂
反应性
脂质体
抗体
疟疾疫苗
恶性疟原虫
化学
免疫
病毒学
疟疾
生物
分子生物学
免疫学
生物化学
作者
Wei‐Chiao Huang,Bingbing Deng,Cuiyan Lin,Kevin A. Carter,Jumin Geng,Aida Razi,Xuedan He,Upendra Chitgupi,Jasmin Federizon,Boyang Sun,Carole A. Long,Joaquı́n Ortega,Sandeep Dutta,C. Richter King,Kazutoyo Miura,Shwu‐Maan Lee,Jonathan F. Lovell
标识
DOI:10.1038/s41565-018-0271-3
摘要
Pfs25 is a malaria transmission-blocking vaccine antigen candidate, but its apparently limited immunogenicity in humans has hindered clinical development. Here, we show that recombinant, polyhistidine-tagged (his-tagged) Pfs25 can be mixed at the time of immunization with pre-formed liposomes containing cobalt porphyrin–phospholipid, resulting in spontaneous nanoliposome antigen particleization (SNAP). Antigens are stably presented in uniformly orientated display via his-tag insertion in the cobalt porphyrin–phospholipid bilayer, without covalent modification or disruption of antigen conformation. SNAP immunization of mice and rabbits is well tolerated with minimal local reactogenicity, and results in orders-of-magnitude higher functional antibody generation compared with other ‘mix-and-inject’ adjuvants. Serum-stable antigen binding during transit to draining lymph nodes leads to enhanced antigen uptake by phagocytic antigen-presenting cells, with subsequent generation of long-lived, antigen-specific plasma cells. Seamless multiplexing with four additional his-tagged Plasmodium falciparum polypeptides induces strong and balanced antibody production, illustrating the simplicity of developing multistage particulate vaccines with SNAP immunization. Mixing antigens with liposomes containing cobalt porphyrin leads to the spontaneous formation of a malaria nanovaccine with increased uptake by phagocytic antigen-presenting cells, boosting the production of long-lasting functional antibodies in mice and rabbits.
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