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Nano Lett. 2018 May 9;18(5):3007-3016. doi: 10.1021/acs.nanolett.8b00478. Epub 2018 Apr 30.

Potency of a Scalable Nanoparticulate Subunit Vaccine.

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Center for Functional Biomaterials, School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education , Sun Yat-sen University , Guangzhou 510275 , China.
Sinovac Biotech Co. Ltd , No. 39 Shangdi Xi Road , Beijing 100085 , China.
Department of Materials Science and Engineering, and Institute for NanoBioTechnology , Johns Hopkins University , Baltimore , Maryland 21218 , United States.
Department of Biomedical Engineering , Columbia University , New York , New York 10027 , United States.


Nanoparticulate vaccines can potentiate immune responses by site-specific drainage to lymph nodes (LNs). This approach may benefit from a nanoparticle engineering method with fine control over size and codelivery of antigen and adjuvant. Here, we applied the flash nanocomplexation (FNC) method to prepare nanovaccines via polyelectrolyte complexation of chitosan and heparin to coencapsulate the VP1 protein antigen from enterovirus 71, which causes hand-foot-mouth disease (HFMD), with tumor necrosis factor α (TNF) or CpG as adjuvants. FNC allows for reduction of the nanovaccine size to range from 90 to 130 nm with relatively narrower size distribution and a high payload capacity. These nanovaccines reached both proximal and distal LNs via subcutaneous injection and subsequently exhibited prolonged retention in the LNs. The codelivery induced strong immune activation toward a Th1 response in addition to a potent Th2 response, and conferred effective protection against lethal virus challenge comparable to that of an approved inactivated viral vaccine in mouse models of both passive and active immunization setting. In addition, these nanovaccines also elicited strong IgA titers, which may offer unique advantages for mucosal protection. This study addresses the issues of size control, antigen bioactivity retention, and biomanufacturing to demonstrate the translational potential of a subunit nanovaccine design.


Adjuvant; codelivery; cross-presentation; lymph node targeting; subunit nanovaccine

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