Modulation of protective immunity against herpes simplex virus via mucosal genetic co-transfer of DNA vaccine with beta2-adrenergic agonist.
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 beta(2)-adrenergic agonist salbutamol may have modulatory functions of immunity induced by DNA vaccine, since beta(2)-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.
Kim
Seong Bum
SB
Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju 561-756, Korea.
Han
Young Woo
YW
Rahman
M M
MM
Kim
Seon Ju
SJ
Yoo
Dong Jin
DJ
Kang
Seong Ho
SH
Kim
Koanhoi
K
Eo
Seong Kug
SK
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000276:immunology / Q000494:pharmacology*; D000420:Albuterol / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines; D018928:Immunity, Mucosal / Q000187:drug effects* / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D018139:Simplexvirus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000318:Adrenergic beta-Agonists; D000914:Antibodies, Viral; D016207:Cytokines; D022301:Herpes Simplex Virus Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D000420:Albuterol