Microneedle Delivery of H5N1 Influenza Virus-Like Particles to the Skin Induces Long-Lasting B- and T-Cell Responses in Mice

American Society for Microbiology - Tập 17 Số 9 - Trang 1381-1389 - 2010
Jae-Min Song1,2,3,4, Yeu‐Chun Kim1,2,3,4, Aleksandr S. Lipatov1,2,3,4, Marc Pearton1,2,3,4, C. Todd Davis1,2,3,4, Dae‐Goon Yoo1,2,3,4, Kyoung‐mi Park1,2,3,4, Li-Mei Chen1,2,3,4, Fu‐Shi Quan1,2,3,4, James C. Birchall1,2,3,4, Ruben O. Donis1,2,3,4, Mark R. Prausnitz1,2,3,4, Richard W. Compans1,2,3,4, Sang‐Moo Kang1,2,3,4
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia
2Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30322
3School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30232
4Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3NB, United Kingdom

Tóm tắt

ABSTRACTA simple method suitable for self-administration of vaccine would improve mass immunization, particularly during a pandemic outbreak. Influenza virus-like particles (VLPs) have been suggested as promising vaccine candidates against potentially pandemic influenza viruses, as they confer long-lasting immunity but are not infectious. We investigated the immunogenicity and protective efficacy of influenza H5 VLPs containing the hemagglutinin (HA) of A/Vietnam/1203/04 (H5N1) virus delivered into the skin of mice using metal microneedle patches and also studied the response of Langerhans cells in a human skin model. Prime-boost microneedle vaccinations with H5 VLPs elicited higher levels of virus-specific IgG1 and IgG2a antibodies, virus-specific antibody-secreting cells, and cytokine-producing cells up to 8 months after vaccination compared to the same antigen delivered intramuscularly. Both prime-boost microneedle and intramuscular vaccinations with H5 VLPs induced similar hemagglutination inhibition titers and conferred 100% protection against lethal challenge with the wild-type A/Vietnam/1203/04 virus 16 weeks after vaccination. Microneedle delivery of influenza VLPs to viable human skin using microneedles induced the movement of CD207+Langerhans cells toward the basement membrane. Microneedle vaccination in the skin with H5 VLPs represents a promising approach for a self-administered vaccine against viruses with pandemic potential.

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