title: Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody responses to a Plasmodium falciparum blood-stage vaccine.
abstract: The efficacy of vaccine adjuvants can be influenced by the immunological environment of the host, depending on the mechanism(s) by which they exert their immunopotentiating activities. Interleukin-6 is a pleiotropic cytokine that has a broad range of biological activities on immune and non-immune cells. We investigated the role of IL-6 on the ability of nine adjuvant formulations to induce antibody responses to the Plasmodium falciparum MSP1-19 malaria vaccine, using IL-6-/- (KO) mice. Results showed that some adjuvants, i.e. MPL-SE, CFA/IFA, ISA720/QS21/MPL, depended on IL-6 for their efficacy, while others exhibited increased potency in its absence. The efficacy of adjuvants in the IL-6 KO environment cannot be solely attributed to their ability to stimulate antigen-specific cellular responses, suggesting that other biological activities of IL-6 are also important. The results further suggest that two adjuvants utilized dissimilar pathways to potentiate the same type of immune response.
authors: Department of Tropical Medicine and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, United States. ghui@hawaii.edu
authors: George
authors: G
authors: Hui
authors: Caryn
authors: C
authors: Hashimoto
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010963:Plasmodium falciparum / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007136:Immunoglobulins; D015850:Interleukin-6; D017780:Malaria Vaccines
references: Vaccine. 1997 Feb;15(2):176-8
references: 9066035
references: J Immunol Methods. 1997 May 12;204(1):57-66
references: 9202710
references: J Immunol. 1998 May 15;160(10):5007-17
references: 9590250
references: Infect Immun. 1998 Nov;66(11):5329-36
references: 9784540
references: J Virol. 2005 Feb;79(3):1343-50
references: 15650160
references: Crit Rev Immunol. 2004;24(5):297-320
references: 15663361
references: Nat Med. 2005 Apr;11(4 Suppl):S63-8
references: 15812492
references: Vet Res. 2005 Sep-Dec;36(5-6):827-38
references: 16120256
references: Curr Opin Immunol. 2005 Oct;17(5):476-9
references: 16054352
references: J Immunol. 2005 Sep 15;175(6):3463-8
references: 16148087
references: Chem Immunol Allergy. 2006;90:65-81
references: 16210903
references: Parasitology. 2005;130 Suppl:S11-25
references: 16281988
references: Infect Immun. 2006 Apr;74(4):2138-44
references: 16552043
references: Curr Dir Autoimmun. 2005;8:124-39
references: 15564719
references: Immunol Res. 1999;20(2):101-8
references: 10580635
references: Immunol Res. 1999;20(2):109-15
references: 10580636
references: Immunol Res. 1999;20(2):117-26
references: 10580637
references: Int Immunol. 2000 Jun;12(6):807-15
references: 10837408
references: Infect Immun. 2000 Oct;68(10):5509-16
references: 10992447
references: Infect Immun. 2001 Mar;69(3):1454-62
references: 11179312
references: Infect Immun. 2001 Mar;69(3):1708-13
references: 11179347
references: Nat Immunol. 2000 Dec;1(6):510-4
references: 11101873
references: Protein Expr Purif. 2001 Dec;23(3):468-75
references: 11722185
references: Int Arch Allergy Immunol. 2001 Oct;126(2):135-9
references: 11729351
references: J Immunol. 2002 Jan 15;168(2):926-32
references: 11777991
references: Front Biosci. 2002 May 1;7:d1056-183
references: 11991846
references: Infect Immun. 2002 Aug;70(8):4215-25
references: 12117930
references: Pharm Res. 2002 Jun;19(6):715-28
references: 12134940
references: Vaccine. 2002 Sep 10;20(27-28):3292-303
references: 12213399
references: Mol Immunol. 2002 Dec;39(9):531-6
references: 12431386
references: Science. 2003 Feb 14;299(5609):1033-6
references: 12532024
references: Nat Rev Drug Discov. 2003 Sep;2(9):727-35
references: 12951579
references: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14333-8
references: 14612562
references: J Nutr Health Aging. 2004;8(1):9-18
references: 14730363
references: Aging Cell. 2004 Aug;3(4):161-7
references: 15268749
references: J Virol. 2004 Sep;78(17):9285-94
references: 15308723
references: Immunol Cell Biol. 2004 Oct;82(5):488-96
references: 15479434
references: J Exp Med. 1988 Feb 1;167(2):332-44
references: 3258006
references: Proc Natl Acad Sci U S A. 1989 Aug;86(16):6343-7
references: 2668963
references: J Immunol. 1991 Dec 1;147(11):3935-41
references: 1940375
references: J Exp Med. 1992 Nov 1;176(5):1483-7
references: 1383389
references: J Immunol. 1993 Mar 1;150(5):1838-45
references: 8436819
references: Infect Immun. 1993 Oct;61(10):4126-30
references: 8406801
references: J Immunol. 1994 Apr 1;152(7):3483-90
references: 8144929
references: Mol Biochem Parasitol. 1994 Feb;63(2):283-9
references: 7516493
references: J Immunol Methods. 1995 Apr 12;181(1):45-54
references: 7537312
references: Pharm Biotechnol. 1995;6:277-96
references: 7551221
references: Pharm Biotechnol. 1995;6:495-524
references: 7551233
references: Pharm Biotechnol. 1995;6:525-41
references: 7551234