RESUMO
The 'Nanopatch' (NP) comprises arrays of densely packed projections with a defined geometry and distribution designed to physically target vaccines directly to thousands of epidermal and dermal antigen presenting cells (APCs). These miniaturized arrays are two orders of magnitude smaller than standard needles-which deliver most vaccines-and are also much smaller than current microneedle arrays. The NP is dry-coated with antigen, adjuvant, and/or DNA payloads. After the NP was pressed onto mouse skin, a protein payload co-localized with 91.4 + or - 4.1 APC mm(-2) (or 2925 in total) representing 52% of the delivery sites within the NP contact area, agreeing well with a probability-based model used to guide the device design; it then substantially increases as the antigen diffuses in the skin to many more cells. APC co-localizing with protein payloads rapidly disappears from the application area, suggesting APC migration. The NP also delivers DNA payloads leading to cutaneous expression of encoded proteins within 24 h. The efficiency of NP immunization is demonstrated using an inactivated whole chikungunya virus vaccine and a DNA-delivered attenuated West Nile virus vaccine. The NP thus offers a needle-free, versatile, highly effective vaccine delivery system that is potentially inexpensive and simple to use.
Assuntos
Vírus Chikungunya/imunologia , Nanoestruturas/química , Vacinação/métodos , Vacinas Virais/administração & dosagem , Vacinas contra o Vírus do Nilo Ocidental/administração & dosagem , Administração Cutânea , Infecções por Alphavirus/prevenção & controle , Animais , Células Apresentadoras de Antígenos/imunologia , Febre de Chikungunya , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de DNA/administração & dosagem , Febre do Nilo Ocidental/prevenção & controle , Vacinas contra o Vírus do Nilo Ocidental/genética , Vacinas contra o Vírus do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/imunologiaRESUMO
Dry-coated microprojections (MPs) deliver vaccine to abundant immunogenic cells within the skin to induce immune responses. Success in this targeted vaccine delivery relies on overcoming the challenges of dry-coating the vaccine onto the very small (Assuntos
Anticorpos/sangue
, Sistemas de Liberação de Medicamentos
, Imunoterapia/métodos
, Nanotecnologia
, Ovalbumina/administração & dosagem
, Tecnologia Farmacêutica/métodos
, Vacinas/administração & dosagem
, Administração Cutânea
, Animais
, Química Farmacêutica
, Formas de Dosagem
, Composição de Medicamentos
, Feminino
, Injeções Intramusculares
, Camundongos
, Camundongos Endogâmicos C57BL
, Microinjeções
, Ovalbumina/química
, Ovalbumina/farmacocinética
, Absorção Cutânea
, Propriedades de Superfície
, Vacinas/química
, Vacinas/farmacocinética