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Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination.


ABSTRACT: Sustained exposure of lymphoid tissues to vaccine antigens promotes humoral immunity, but traditional bolus immunizations lead to rapid antigen clearance. We describe a technology to tailor vaccine kinetics in a needle-free platform translatable to human immunization. Solid pyramidal microneedle (MN) arrays were fabricated with silk fibroin protein tips encapsulating a stabilized HIV envelope trimer immunogen and adjuvant, supported on a dissolving polymer base. Upon brief skin application, vaccine-loaded silk tips are implanted in the epidermis/upper dermis where they release vaccine over a time period determined by the crystallinity of the silk matrix. Following MN immunization in mice, Env trimer was released over 2 wk in the skin, correlating with increased germinal center (GC) B cell responses, a ?1,300-fold increase in serum IgG titers and a 16-fold increase in bone marrow (BM) plasma cells compared with bolus immunization. Thus, implantable MNs provide a practical means to substantially enhance humoral immunity to subunit vaccines.

SUBMITTER: Boopathy AV 

PROVIDER: S-EPMC6697788 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination.

Boopathy Archana V AV   Mandal Anasuya A   Kulp Daniel W DW   Menis Sergey S   Bennett Nitasha R NR   Watkins Hannah C HC   Wang Wade W   Martin Jacob T JT   Thai Nikki T NT   He Yanpu Y   Schief William R WR   Hammond Paula T PT   Irvine Darrell J DJ  

Proceedings of the National Academy of Sciences of the United States of America 20190729 33


Sustained exposure of lymphoid tissues to vaccine antigens promotes humoral immunity, but traditional bolus immunizations lead to rapid antigen clearance. We describe a technology to tailor vaccine kinetics in a needle-free platform translatable to human immunization. Solid pyramidal microneedle (MN) arrays were fabricated with silk fibroin protein tips encapsulating a stabilized HIV envelope trimer immunogen and adjuvant, supported on a dissolving polymer base. Upon brief skin application, vacc  ...[more]

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