title: Efficacy evaluation of two synthetic lysine lipidated tripeptides as vaccine adjuvants against HBsAg.
abstract: In the present investigation, adjuvant potential of two novel lipidated tripeptide lysine derivatives (KKSM and KKSMB) was evaluated using various in vitro and animal-derived models of humoral and cell-mediated immune events in response to hepatitis B surface antigen (HBsAg). The results were compared with alum adjuvanted with HBsAg. Both these molecules were found to stimulate anti-HBsAg IgG and neutralizing (IgG1 and IgG2a) antibody titres in mice sera. The two molecules stimulated the proliferation of T-lymphocyte sub-sets (CD4/CD8) as well as the production of soluble mediators of Th1 (IL-2 and IFN-γ) and Th2 response (IL-4) in spleen cell culture supernatant. Furthermore, the two lipidated tripeptides enhanced the CD4, CD8, CD3 and CD19 cell populations as well as CD4/CD8 derived IL-2, IL-4, IFN-γ and TNF-α in whole blood of treated mice. There was found to be the significant enhancement in the release of IL-12, IFN-γ and nitrite content in macrophage supernatant. Moreover, the two lipidated tripeptides enhanced the population of CD80 and CD86 in spleen-derived macrophages and did not show any hemolytic effect on rabbit RBCs. Taken together, these results suggest that both these molecules are the potent enhancers of anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner.
authors.affiliation: Division of Pharmacology, Indian Institute of Integrative Medicine (CSIR), Jammu-180001, India.
authors.forename: Tabasum
authors.initials: T
authors.lastname: Sidiq
authors.forename: Anamika
authors.initials: A
authors.lastname: Khajuria
authors.forename: Syed
authors.initials: S
authors.lastname: Shafi
authors.forename: Tabasum
authors.initials: T
authors.lastname: Ismail
authors.forename: Halmathur
authors.initials: H
authors.lastname: Sampath Kumar
authors.forename: Vellimedu
authors.initials: V
authors.lastname: Kannappa Srinivas
authors.forename: Ella
authors.initials: E
authors.lastname: Krishna
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kamal Johri
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G / Q000097:blood; D008055:Lipids / Q000737:chemistry; D008239:Lysine / Q000737:chemistry*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D008055:Lipids; D009573:Nitrites; D009842:Oligopeptides; D008239:Lysine