Exp Mol Med.
2009 Nov;41(11):812-823. 10.3858/emm.2009.41.11.087.
Modulation of protective immunity against herpes simplex virus via mucosal genetic co-transfer of DNA vaccine with beta2-adrenergic agonist
- Affiliations
-
- 1Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju 561-756, Korea. vetvirus@chonbuk.ac.kr
- 2Department of Chemistry, Seonam University, Namwon 590-711, Korea.
- 3Department of Chemistry and Research Institute of Physics and Chemistry (RINPAC), Chonbuk National University, Jeonju 561-756, Korea.
- 4Department of Pharmacology, School of Medicine, Pusan National University, Busan 602-739, Korea.
- KMID: 1122282
- DOI: http://doi.org/10.3858/emm.2009.41.11.087
Abstract
- Cholera toxin, which has been frequently used as mucosal adjuvant, leads to an irreversible activation of adenylyl cyclase, thereby accumulating cAMP in target cells. Here, it was assumed that beta2-adrenergic agonist salbutamol may have modulatory functions of immunity induced by DNA vaccine, since beta2-adrenergic agonists induce a temporary cAMP accumulation. To test this assumption, the present study evaluated the modulatory functions of salbutamol co-administered with DNA vaccine expressing gB of herpes simplex virus (HSV) via intranasal (i.n.) route. We found that the i.n. co-administration of salbutamol enhanced gB-specific IgG and IgA responses in both systemic and mucosal tissues, but optimal dosages of co-administered salbutamol were required to induce maximal immune responses. Moreover, the mucosal co-delivery of salbutamol with HSV DNA vaccine induced Th2-biased immunity against HSV antigen, as evidenced by IgG isotypes and Th1/Th2-type cytokine production. The enhanced immune responses caused by co-administration of salbutamol provided effective and rapid responses to HSV mucosal challenge, thereby conferring prolonged survival and reduced inflammation against viral infection. Therefore, these results suggest that salbutamol may be an attractive adjuvant for mucosal genetic transfer of DNA vaccine.
Keyword
MeSH Terms
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Adjuvants, Immunologic/*pharmacology
Adrenergic beta-Agonists/immunology/*pharmacology
Albuterol/immunology/*pharmacology
Animals
Antibodies, Viral/immunology
Cercopithecus aethiops
Cytokines/immunology
Dose-Response Relationship, Drug
Dose-Response Relationship, Immunologic
Herpes Simplex/immunology/*prevention & control
Herpes Simplex Virus Vaccines
Immunity, Mucosal/*drug effects/immunology
Immunoglobulin A/immunology
Immunoglobulin G/immunology
Mice
Simplexvirus/*immunology
Th1 Cells/immunology
Th2 Cells/immunology
Vaccines, DNA/*immunology/pharmacology
Vero Cells
Viral Envelope Proteins/immunology
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