TNFalpha Kinoid Vaccination-induced Neutralizing Antibodies to TNFalpha Protect Mice from Autologous TNFalpha-driven Chronic and Acute Inflammation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Dec 13

PMID 17158801

Citations 31

Authors

Helene Le Buanec

Laure Delavallee

Natacha Bessis

Sebastien Paturance

Bernard Bizzini

Robert Gallo

Daniel Zagury

Marie-Christophe Boissier

Affiliations

Soon will be listed here.

Abstract

The proinflammatory cytokine TNFalpha is a potent mediator of septic shock and a therapeutic target for chronic inflammatory pathologies including rheumatoid arthritis and Crohn's disease. As an alternative to anti-human TNFalpha (hTNFalpha) mAbs and other hTNFalpha blocker approved drugs, we developed an active anti-hTNFalpha immunotherapy, based on a vaccine comprised of a keyhole limpet hemocyanin-hTNFalpha heterocomplex immunogen (hTNFalpha kinoid) adjuvanted in incomplete Freund's adjuvant. In mice transgenic for hTNFalpha (TTg mice), hTNFalpha kinoid vaccination elicited high titers of Abs that neutralized hTNFalpha bioactivities but did not result in a cellular response to hTNFalpha. The vaccine was safe and effective in two experimental models. Kinoid-immunized but not control TTg mice resisted hTNFalpha-driven shock in one model and were prevented from spontaneous arthritis, inflammatory synovitis, and articular destruction in a second model. These data demonstrate an anti-cytokine induction of autoimmune protection against both acute and chronic hTNFalpha exposure. They show that active vaccination against a human cytokine can be achieved, and that the immune response can be effective and safe.

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References

Chaudhari U, Romano P, Mulcahy L, Dooley L, Baker D, Gottlieb A . Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet. 2001; 357(9271):1842-7. DOI: 10.1016/s0140-6736(00)04954-0. View

Keffer J, Probert L, Cazlaris H, Georgopoulos S, KASLARIS E, Kioussis D . Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J. 1991; 10(13):4025-31. PMC: 453150. DOI: 10.1002/j.1460-2075.1991.tb04978.x. View

Bessis N, Guery L, Mantovani A, Vecchi A, Sims J, Fradelizi D . The type II decoy receptor of IL-1 inhibits murine collagen-induced arthritis. Eur J Immunol. 2000; 30(3):867-75. DOI: 10.1002/1521-4141(200003)30:3<867::AID-IMMU867>3.0.CO;2-M. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Miellot A, Zhu R, Diem S, Boissier M, Herbelin A, Bessis N . Activation of invariant NK T cells protects against experimental rheumatoid arthritis by an IL-10-dependent pathway. Eur J Immunol. 2005; 35(12):3704-13. DOI: 10.1002/eji.200535235. View

Charles P, Smeenk R, de Jong J, Feldmann M, Maini R . Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials. Arthritis Rheum. 2000; 43(11):2383-90. DOI: 10.1002/1529-0131(200011)43:11<2383::AID-ANR2>3.0.CO;2-D. View

Le Loet X, Lequerre T, Vittecoq O . Rheumatoid arthritis in 2005: which patients should receive TNFalpha antagonists and when? A point of view. Joint Bone Spine. 2005; 72(6):447-50. DOI: 10.1016/j.jbspin.2005.05.003. View

Salfeld J . Use of new biotechnology to design rational drugs against newly defined targets. Best Pract Res Clin Rheumatol. 2004; 18(1):81-95. DOI: 10.1016/j.berh.2003.10.001. View

Hommes D, van Deventer S . Targeting tumor necrosis factor-alpha in inflammatory bowel disease: why, how, and when?. Curr Opin Gastroenterol. 2005; 19(4):350-7. DOI: 10.1097/00001574-200307000-00005. View

10.

Williams R, Feldmann M, Maini R . Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 1992; 89(20):9784-8. PMC: 50217. DOI: 10.1073/pnas.89.20.9784. View

11.

Lehmann V, Freudenberg M, Galanos C . Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med. 1987; 165(3):657-63. PMC: 2188282. DOI: 10.1084/jem.165.3.657. View

12.

Zagury D, Burny A, Gallo R . Toward a new generation of vaccines: the anti-cytokine therapeutic vaccines. Proc Natl Acad Sci U S A. 2001; 98(14):8024-9. PMC: 35461. DOI: 10.1073/pnas.141224798. View

13.

Day R . Adverse reactions to TNF-alpha inhibitors in rheumatoid arthritis. Lancet. 2002; 359(9306):540-1. DOI: 10.1016/S0140-6736(02)07718-8. View

14.

Dalum I, Butler D, Jensen M, Hindersson P, Steinaa L, Waterston A . Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol. 1999; 17(7):666-9. DOI: 10.1038/10878. View

15.

Saidenberg-Kermanach N, Corrado A, Lemeiter D, DeVernejoul M, Boissier M, Cohen-Solal M . TNF-alpha antibodies and osteoprotegerin decrease systemic bone loss associated with inflammation through distinct mechanisms in collagen-induced arthritis. Bone. 2004; 35(5):1200-7. DOI: 10.1016/j.bone.2004.07.004. View

16.

Gray D, Skarvall H . B-cell memory is short-lived in the absence of antigen. Nature. 1988; 336(6194):70-3. DOI: 10.1038/336070a0. View

17.

Zagury D, Le Buanec H, Bizzini B, Burny A, Lewis G, Gallo R . Active versus passive anti-cytokine antibody therapy against cytokine-associated chronic diseases. Cytokine Growth Factor Rev. 2003; 14(2):123-37. DOI: 10.1016/s1359-6101(03)00004-2. View

18.

Chackerian B, Lowy D, Schiller J . Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies. J Clin Invest. 2001; 108(3):415-23. PMC: 209354. DOI: 10.1172/JCI11849. View

19.

Feldmann M, Maini R . Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med. 2003; 9(10):1245-50. DOI: 10.1038/nm939. View

20.

Wildbaum G, Youssef S, Karin N . A targeted DNA vaccine augments the natural immune response to self TNF-alpha and suppresses ongoing adjuvant arthritis. J Immunol. 2000; 165(10):5860-6. DOI: 10.4049/jimmunol.165.10.5860. View