Modulation of protective immunity against herpes simplex virus via mucosal genetic co-transfer of DNA vaccine with β2-adrenergic agonist

다국어 초록 (Multilingual 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 β2-adrenergic agonist salbutamol may have modulatory functions of immunity induced by DNA vaccine, since β2-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.

참고문헌 (Reference)

1 Panina-Bordignon P, "β2-agonists prevent Th1 development by selective inhibition of interleukin-12" 100 : 1513-1519, 1997

2 Pope M, "Transmission, acute HIV-1 infection and the quest for strategies to prevent infection" 9 : 847-852, 2003

3 Strosberg AD, "Structure, function and regulation of the β-adrenergic receptors. In Recombinant cell surface receptors" Landes Company 57-76, 1997

4 Fermin Z, "Ricciardi-Castagnoli P, Hoebeke J. Salbutamol as an adjuvant for nasal vaccination" 17 : 1936-1941, 1999

5 Yoon, Hyun A, "Protective Immunity Induced by Systemic and Mucosal Delivery of DNAVaccine Expressing Glycoprotein B of Pseudorabies Virus" 한국미생물·생명공학회 18 (18): 591-599, 2008

6 Young Woo Han, "Polarization of protective immunity induced by replication-incompetent adenovirus expressing glycoproteins of pseudorabies virus" 생화학분자생물학회 40 (40): 583-595, 2008

7 Davis SS, "Nasal Vaccines" 51 : 21-42, 2001

8 Ogra PL, "Mucosal immunity and infections. In Mucosal Immunology" Academic Press 655-, 1999

9 Freytag LC, "Mucosal adjuvants" 23 : 1804-1813, 2005

10 Eo SK, "Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines" 75 : 569-578, 2001a

11 Partidos CD, "Intranasal vaccines: forthcoming challenges" 3 : 273-280, 2000

12 Klavinskis LS, "Intranasal immunization with plasmid DNA-lipid complexes elicits mucosal immunity in the female genital and rectal tracts" 162 : 254-262, 1999

13 Lamm ME, "Interaction of antigens and antibodies at mucosal surfaces" 51 : 311-340, 1997

14 Kuklin N, "Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization" 71 : 3138-3145, 1997

15 Eo SK, "Immunopotentiation of DNA vaccine against herpes simplex virus via co-delivery of plasmid DNA expressing CCR7 ligands" 19 : 4685-4693, 2001b

16 Agren LC, "Genetically engineered non-toxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit" 158 : 3936-3946, 1997

17 Elson CO, "Generalized systemic and mucosal immunity in mice after mucosal immunization with cholera toxin" 132 : 2736-2741, 1984

18 Gautam A, "Enhanced gene expression in mouse lung after PEI-DNA aerosol delivery" 2 : 63-70, 2000

19 Donnelly JJ, "DNA vaccines" 15 : 617-648, 1997

20 Lycke N, "Cholera toxin promotes B cell isotype switch by two different mechanisms cAMP induction augments germ-line Ig H chain RNA transcripts where membrane ganglioside GM1-receptor binding enhances later events in differentiation" 150 : 4810-4821, 1993

21 Leal-Berumen I, "Cholera toxin increases IL-6 synthesis and decreases TNF-alpha production by rat peritoneal mast cells" 156 : 316-321, 1996

22 MacLaughlin FC, "Chitosan and depolymerized chitosan oligomers as condensing carriers for in vivo plasmid delivery" 56 : 259-272, 1998

23 Hoffman BB, "Catecholamines and sympathommetic drugs. In Goodman and Gilman's the pharmacological basis of therapeutics" Pergamon Press 187-218, 1990

24 Botta F, "Adrenergic modulation of dendritic cell cancer vaccine in a mouse model: role of dendritic cell maturation" 31 : 263-270, 2008

25 Heckert RA, "A novel transcutaneous plasmid-dimethylsulfoxide delivery technique for avian nucleic acid immunization" 89 : 67-81, 2002

26 Parr MB, "A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type2" 70 : 369-380, 1994

27 Lycke N, "A molecular approach to the construction of an effective mucosal vaccine adjuvant: studies based on cholera toxin ADP-ribosylation and cell targeting. In Essentials of mucosal immunology" Academic Press 563-581, 1996

28 Fukuiwa T, "A combination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity" 26 : 4849-4859, 2008