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Co-delivery of antigen and dual agonists by programmed mannose-targeted cationic lipid-hybrid polymersomes for enhanced vaccination

Zhu, Dunwan, Hu, Chunyan, Fan, Fan, Qin, Yu, Huang, Chenlu, Zhang, Zhiming, Lu, Lu, Wang, Hai, Sun, Hongfan, Leng, Xigang, Wang, Chun, Kong, Deling, Zhang, Linhua
Biomaterials 2019 v.206 pp. 25-40
CD8-positive T-lymphocytes, Toll-like receptor 4, agonists, antigens, cytokines, dendritic cells, humoral immunity, hydrophobicity, immune response, injection site, lipid A, lymph nodes, lymphocyte proliferation, mannose, mice, moieties, neoplasms, ovalbumin, secretion, subunit vaccines, vaccination
Exploiting Toll-like receptor (TLR) agonists or their certain combinations can enhance the immune potency of subunit vaccine. Nevertheless, the design of co-delivery systems which can act in a synergistic and spatio-temporal way to achieve effective and durable specific immune response is still challenging. Here we fabricated mannose-functionalized lipid-hybrid polymersomes (MAN-IMO-PS) for co-delivery of ovalbumin antigen both inside the inner core and outside the lipid layer, TLR7/8 agonist imiquimod within the hydrophobic membrane, TLR4 agonist monophosphoryl lipid A in the lipid layer as programmed nanovaccine to synergistically activate immune responses for improving vaccine efficacy. After efficiently internalized by dendritic cells via mannose targeting and TLR4 ligating, MAN-IMO-PS significantly enhanced cross-presentation and cytokine production. In addition, MAN-IMO-PS showed depot effect at the injection site and enhanced migration to draining lymph nodes. Mice immunized with MAN-IMO-PS elicited greater lymphocyte activation, CD4+ and CD8+ T cell response, effector cytokines secretion, and induced Th-1 biased humoral responses. More importantly, prophylactic vaccination by MAN-IMO-PS significantly delayed tumor occurrence, suppressed tumor growth with prolonged survival, and achieved long-term immune effect. The present study demonstrates a rationally designed nanovaccine for combining antigen, different TLR agonists, and targeting moiety in a programmed manner to induce synergistic antitumor immune response.