A single sublingual dose of an adenovirus-based vaccine protects against lethal Ebola challenge in mice and guinea pigs.
Mol Pharm
; 9(1): 156-67, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22149096
ABSTRACT
Sublingual (SL) delivery, a noninvasive immunization method that bypasses the intestinal tract for direct entry into the circulation, was evaluated with an adenovirus (Ad5)-based vaccine for Ebola. Mice and guinea pigs were immunized via the intramuscular (IM), nasal (IN), oral (PO) and SL routes. SL immunization elicited strong transgene expression in and attracted CD11c(+) antigen presenting cells to the mucosa. A SL dose of 1 × 108 infectious particles induced Ebola Zaire glycoprotein (ZGP)-specific IFN-γ⺠T cells in spleen, bronchoalveolar lavage, mesenteric lymph nodes and submandibular lymph nodes (SMLN) of naive mice in a manner similar to the same dose given IN. Ex vivo CFSE and in vivo cytotoxic T lymphocyte (CTL) assays confirmed that SL immunization elicits a notable population of effector memory CD8+ T cells and strong CTL responses in spleen and SMLN. SL immunization induced significant ZGP-specific Th1 and Th2 type responses unaffected by pre-existing immunity (PEI) that protected mice and guinea pigs from lethal challenge. SL delivery protected more mice with PEI to Ad5 than IM injection. SL immunization also reduced systemic anti-Ad5 T and B cell responses in naive mice and those with PEI, suggesting that secondary immunizations could be highly effective for both populations.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença pelo Vírus Ebola
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Vacinas contra Ebola
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Ebolavirus
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Antígenos Virais
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article