title: RLJ-NE-299A: a new plant based vaccine adjuvant.
abstract: Alum has been in use since long as an adjuvant for vaccines. However, its use as a vaccine adjuvant offers limitation in supporting cell mediated response. Therefore, a new plant based product RLJ-NE-299A from Picrorhiza kurroa reported for its immunostimulatory activity, has been explored for its potential as an alternative adjuvant. In order to compare the adjuvant activity with alum, antigen-specific immune responses were evaluated following immunization with a formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with RLJ-NE-299A and alum in mice. The adjuvant RLJ-NE-299A up-regulated remarkably the expression of Th1 cytokines IL-2, IL-12, IFN-gamma, TNF alpha and Th2 cytokine IL-4 in lymph node cell cultures after 2 weeks of primary immunization with HBsAg. Further, the levels of both immunoglobulins IgG2a (Th1) and IgG1 (Th2) subtypes increased profoundly in blood sera of mice immunized with HBsAg/RLJ-NE-299A. The results indicated that RLJ-NE-299A has strong potential to increase both cell mediated and humoral immune responses and is capable of sustaining the total antigen-specific antibody response. Besides, the RLJ-NE-299A provides a signal to gear up both CD4 helper cells (Th1 and Th2) and CD8 cells populations, which may have important implications for vaccination against hepatitis B virus. Variable doses of RLJ-NE-299A (0.312-40 microg) containing vaccine antigen (HBsAg) were well tolerated with optimum T cell response at 2.5 microg/ml. Not only this, the adjuvant was also able to induce cellular immune responses to HBsAg as evidenced by Th1 and Th2 cytokines upregulation, which enabled mice to overcome the unresponsiveness to antigen HBsAg encountered with alum-adjuvanted vaccine in otherwise non-responding mice population. The study presents evidence that the HPLC standardized fraction RLJ-NE-299A, is an adjuvant of choice over alum in improving and maintaining the improved immune status against HBsAg, and may also prove useful adjuvant candidate with other vaccine antigens, too.
authors.affiliation: Division of Pharmacology, Regional Research Laboratory (CSIR), Jammu 180001, India. anamikakhajuria@yahoo.com
authors.forename: Anamika
authors.initials: A
authors.lastname: Khajuria
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.forename: Surjeet
authors.initials: S
authors.lastname: Singh
authors.forename: Fayaz
authors.initials: F
authors.lastname: Malik
authors.forename: Jaswant
authors.initials: J
authors.lastname: Singh
authors.forename: K A
authors.initials: KA
authors.lastname: Suri
authors.forename: N K
authors.initials: NK
authors.lastname: Satti
authors.forename: G N
authors.initials: GN
authors.lastname: Qazi
authors.forename: V K
authors.initials: VK
authors.lastname: Srinivas
authors.lastname: Gopinathan
authors.forename: Krishna
authors.initials: K
authors.lastname: Ella
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005434:Flow Cytometry; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D032261:Picrorhiza / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D016207:Cytokines; D004338:Drug Combinations; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D057888:Iridoid Glucosides; D039823:Iridoids; D014612:Vaccines; C520472:picroside I, picroside II drug combination; C041524:aluminum sulfate