A single sublingual dose of an adenovirus-based vaccine protects against lethal ebola challenge in mice and guinea pigs

Jin Huk Choi, Stephen C. Schafer, Lihong Zhang, Gary P. Kobinger, Terry Juelich, Alexander Freiberg, Maria A. Croyle

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 × 10 8 infectious particles induced Ebola Zaire glycoprotein (ZGP)-specific IFN-γ + 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.

Original languageEnglish (US)
Pages (from-to)156-167
Number of pages12
JournalMolecular Pharmaceutics
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Adenovirus Vaccines
Immunization
Guinea Pigs
Democratic Republic of the Congo
Immunity
Lymph Nodes
Cytotoxic T-Lymphocytes
T-Lymphocytes
Nose
Ebola Vaccines
CD11c Antigens
Glycoproteins
Spleen
Jejunoileal Bypass
Secondary Immunization
Intramuscular Injections
Bronchoalveolar Lavage
Antigen-Presenting Cells
Transgenes
Adenoviridae

Keywords

  • adenovirus 5
  • CD4 T cell
  • Ebola Zaire
  • guinea pig
  • memory response
  • mouse
  • pre-existing immunity
  • sublingual
  • toxicity
  • vaccine

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

Cite this

A single sublingual dose of an adenovirus-based vaccine protects against lethal ebola challenge in mice and guinea pigs. / Choi, Jin Huk; Schafer, Stephen C.; Zhang, Lihong; Kobinger, Gary P.; Juelich, Terry; Freiberg, Alexander; Croyle, Maria A.

In: Molecular Pharmaceutics, Vol. 9, No. 1, 01.01.2012, p. 156-167.

Research output: Contribution to journalArticle

Choi, Jin Huk ; Schafer, Stephen C. ; Zhang, Lihong ; Kobinger, Gary P. ; Juelich, Terry ; Freiberg, Alexander ; Croyle, Maria A. / A single sublingual dose of an adenovirus-based vaccine protects against lethal ebola challenge in mice and guinea pigs. In: Molecular Pharmaceutics. 2012 ; Vol. 9, No. 1. pp. 156-167.
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