Author: Huang, W.-C.; Deng, B.; Lin, C.; Carter, K.A.; Geng, J.; Razi, A.; He, X.; Chitgupi, U.; Federizon, J.; Sun, B.; Long, C.A.; Ortega, J.; Dutta, S.; King, C.R.; Miura, K.; Lee, S.-M.; Lovell, J.F.
Description: 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.
Subject Headings: Malaria; Vaccine; Antigen binding; Liposomes
Keywords: A malaria vaccine adjuvant based on recombinant antigen binding to liposomes
Publication year: 2018
Journal or book title: Nature Nanotechnology
Volume: 13
Issue: 12
Pages: 1174-1181
Find the full text :Â https://www.nature.com/articles/s41565-018-0271-3
Find more like this one (cited by): https://scholar.google.com/scholar?cites=7568761923690843944&as_sdt=1000005&sciodt=0,16&hl=en
Type: Journal Article
Serial number: 2513