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.
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This study was supported by PATH’s Malaria Vaccine Initiative, and grants from the National Institutes of Health (R21AI122964 and DP5OD017898) and the intramural programme of the National Institute of Allergy and Infectious Diseases/NIH. The authors acknowledge assistance from G. Mlambo and A. Tripathi with immunofluorescence assays, and input from C. Alving and A. Birkett.
W.-C.H., C.R.K., S.-M.L., J.G. and J.F.L are named inventors on a patent application describing this technology. All other authors declare no competing financial interests.
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Huang, WC., Deng, B., Lin, C. et al. A malaria vaccine adjuvant based on recombinant antigen binding to liposomes. Nature Nanotech 13, 1174–1181 (2018). https://doi.org/10.1038/s41565-018-0271-3
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