Extended delivery of vaccines to the skin improves immune responses

JOURNAL OF CONTROLLED RELEASE

卷:304

Article

Joyce, Jessica C.¹  Sella, Hila E.²  Jost, Heather²  Mistilis, Matthew J.³  Esser, E. Stein⁴  Pradhan, Pallab¹  Toy, Randall¹  Collins, Marcus L.²  Rota, Paul A.²  Roy, Krishnendu¹  Skountzou, Ioanna⁴  Compans, Richard W.⁴  Oberste, M. Steven²  Weldon, William C.²  Norman, James J.³  Prausnitz, Mark R.^1,3 

[1] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, 313 Ferst Dr, Atlanta, GA 30332 USA

[2] Ctr Dis Control & Prevent, Div Viral Dis, 1600 Clifton Rd,M-S C22, Atlanta, GA 30333 USA

[3] Georgia Inst Technol, Sch Chem & Biomol Engn, 311 Ferst Dr, Atlanta, GA 30332 USA

[4] Emory Univ, Dept Microbiol & Immunol, 201 Dowman Dr, Atlanta, GA 30322 USA

关键词: Vaccine;    Intradermal delivery;    Route of administration;    Response to vaccination;    Microneedle patch;    Slow release;   

DOI  :  10.1016/j.jconrel.2019.05.006

来源: Elsevier

【 摘 要 】

Vaccines prevent 2-3 million childhood deaths annually; however, low vaccine efficacy and the resulting need for booster doses create gaps in immunization coverage. In this translational study, we explore the benefits of extended release of licensed vaccine antigens into skin to increase immune responses after a single dose in order to design improved vaccine delivery systems. By administering daily intradermal injections of inactivated polio vaccine according to six different delivery profiles, zeroth-order release over 28 days resulted in neutralizing antibody titers equivalent to two bolus vaccinations administered one month apart. Vaccinations following this profile also improved immune responses to tetanus toxoid and subunit influenza vaccine but not a live-attenuated viral vaccine, measles vaccine. Finally, using subunit influenza vaccine, we demonstrated that daily vaccination by microneedle patch induced a potent, balanced humoral immunity with an increased memory response compared to bolus vaccination. We conclude that extended presentation of antigen in skin via intradermal injection or microneedle patch can enhance immune responses and reduce the number of vaccine doses, thereby enabling increased vaccination efficacy.

【 授权许可】

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