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.

Pfs25是一种可阻断疟疾传播的疫苗抗原候选物，但其在人体中明显有限的免疫原性阻碍了临床发展。在这里，我们显示重组的，带有多组氨酸标签的（带有组氨酸标签的）Pfs25在免疫时可以与含有钴卟啉-磷脂的预先形成的脂质体混合，从而导致自发的纳米脂质体抗原颗粒化（SNAP）。抗原通过在钴卟啉-磷脂双分子层中的组氨酸标签插入以稳定的方向稳定地呈现，而没有共价修饰或破坏抗原构象。SNAP免疫小鼠和兔子的耐受性极强，局部反应原性极低，与其他“混合注射”佐剂相比，功能性抗体的产生量级高。在转运至引流淋巴结的过程中，血清稳定的抗原结合会导致吞噬性抗原呈递细胞对抗原的吸收增加，并随后产生长寿命的抗原特异性浆细胞。无缝多路复用，另外四个带有his标签的恶性疟原虫多肽可诱导强大而平衡的抗体产生，从而说明通过SNAP免疫开发多阶段颗粒疫苗的简便性。