Immunodrugs: therapeutic VLP-based vaccines for chronic diseases.

Worldwide, the prevalence of noncommunicable chronic diseases is increasing. The use of vaccines to induce autoantibodies that neutralize disease-related proteins offers a means to effectively and affordably treat such diseases. Twenty vaccines designed to induce therapeutic autoantibodies were clinically tested in the past 12 years. Immunodrugs are therapeutic vaccines comprising virus-like particles (VLPs) covalently conjugated with self-antigens that induce neutralizing autoantibody responses. Four such VLP-based vaccines have been clinically tested and one has achieved proof of principle: a reduction of blood pressure in hypertensive patients. To facilitate preliminary clinical testing, novel nonclinical study programs have been developed. Safety study designs have considered the underlying B and T cell immunology and have examined potential toxicities of vaccine components and primary and secondary pharmacodynamic action of the vaccines.

[1]  M. Bachmann,et al.  Vaccination against GIP for the Treatment of Obesity , 2008, PloS one.

[2]  J. Cornuz,et al.  A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial , 2008, PloS one.

[3]  Martin F. Bachmann,et al.  The coming of age of virus-like particle vaccines , 2008, Biological chemistry.

[4]  Jay K Kolls,et al.  The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation , 2022 .

[5]  H. Volk,et al.  Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study , 2008, The Lancet.

[6]  G. Jennings,et al.  Active immunization with IL‐1 displayed on virus‐like particles protects from autoimmune arthritis , 2008, European journal of immunology.

[7]  P. Bourne,et al.  Antibody-protein interactions: benchmark datasets and prediction tools evaluation , 2007 .

[8]  U. Nydegger.  Immune Complex Pathophysiology , 2007, Annals of the New York Academy of Sciences.

[9]  B. Chackerian,et al.  Virus-like particles: flexible platforms for vaccine development , 2007, Expert review of vaccines.

[10]  T. Kündig,et al.  A Virus-Like Particle-Based Vaccine Selectively Targeting Soluble TNF-α Protects from Arthritis without Inducing Reactivation of Latent Tuberculosis , 2007, The Journal of Immunology.

[11]  David N. Messina,et al.  Evolutionary and Biomedical Insights from the Rhesus Macaque Genome , 2007, Science.

[12]  Allan Vaag,et al.  Interleukin-1-receptor antagonist in type 2 diabetes mellitus. , 2007, The New England journal of medicine.

[13]  G. Jennings,et al.  Designing recombinant vaccines with viral properties: a rational approach to more effective vaccines. , 2007, Current molecular medicine.

[14]  A. Jegerlehner,et al.  TLR9 Signaling in B Cells Determines Class Switch Recombination to IgG2a , 2007, The Journal of Immunology.

[15]  H. Volk,et al.  A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicity , 2007, Journal of hypertension.

[16]  W. Renner,et al.  A second vaccine revolution for the new epidemics of the 21st century. , 2006, Drug discovery today.

[17]  O. Lund,et al.  Prediction of residues in discontinuous B‐cell epitopes using protein 3D structures , 2006, Protein science : a publication of the Protein Society.

[18]  G. Jennings,et al.  Vaccination against IL‐17 suppresses autoimmune arthritis and encephalomyelitis , 2006, European journal of immunology.

[19]  M. Kurrer,et al.  Neutralization of IL‐17 by active vaccination inhibits IL‐23‐dependent autoimmune myocarditis , 2006, European journal of immunology.

[20]  T. Kündig,et al.  Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults. , 2006, The Journal of allergy and clinical immunology.

[21]  K. Schwarz,et al.  Long‐lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation , 2006, European journal of immunology.

[22]  P. Miller,et al.  Denosumab in Postmenopausal Women with Low Bone Mineral Density , 2007 .

[23]  J. Zuckerman.  Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines , 2006, Journal of medical virology.

[24]  G. Burmester,et al.  Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis , 2005, Annals of the rheumatic diseases.

[25]  K. Schwarz,et al.  Protection against Osteoporosis by Active Immunization with TRANCE/RANKL Displayed on Virus-Like Particles , 2005, The Journal of Immunology.

[26]  G. Jennings,et al.  A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity , 2005, European journal of immunology.

[27]  Nick C Fox,et al.  Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial , 2005, Neurology.

[28]  T. Powles,et al.  Phase I study of TNFα AutoVaccIne in Patients with metastatic cancer , 2005, Cancer Immunology, Immunotherapy.

[29]  B. Sandmaier,et al.  Vaccination with Theratope® (STn-KLH) as treatment for breast cancer , 2004, Expert review of vaccines.

[30]  P. S. St George-Hyslop,et al.  Immunotherapy for Alzheimer's disease , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[31]  E. B. Lindblad.  Aluminium adjuvants--in retrospect and prospect. , 2004, Vaccine.

[32]  S. Watson,et al.  A phase II study of G17DT in gastric carcinoma. , 2004, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[33]  S. Akira,et al.  Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8 , 2004, Science.

[34]  K. Schwarz,et al.  Nonmethylated CG Motifs Packaged into Virus-Like Particles Induce Protective Cytotoxic T Cell Responses in the Absence of Systemic Side Effects , 2004, The Journal of Immunology.

[35]  J. Humphreys,et al.  A vaccination strategy for the long-term suppression of androgens in advanced prostate cancer. , 2004, European urology.

[36]  K. Maki,et al.  The safety and immunogenicity of a CETP vaccine in healthy adults. , 2003, Atherosclerosis.

[37]  Morris J. Brown,et al.  Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (PMD3117) in hypertensive subjects. , 2003, Clinical science.

[38]  G. Comi,et al.  Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice. , 2003, Brain : a journal of neurology.

[39]  Joy A. Cavagnaro,et al.  Preclinical safety evaluation of biotechnology-derived pharmaceuticals , 2002, Nature Reviews Drug Discovery.

[40]  F. Verdier.  Non-clinical vaccine safety assessment. , 2002, Toxicology.

[41]  I. Krull,et al.  Characterization of noncovalent complexes of recombinant human monoclonal antibody and antigen using cation exchange, size exclusion chromatography, and BIAcore. , 2001, Analytical biochemistry.

[42]  G. Kinghorn,et al.  Imiquimod and resiquimod as novel immunomodulators. , 2001, The Journal of antimicrobial chemotherapy.

[43]  C. Benoist,et al.  Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? , 2001, Nature Immunology.

[44]  D. Lowy,et al.  Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies. , 2001, The Journal of clinical investigation.

[45]  M. Schiff,et al.  Role of interleukin 1 and interleukin 1 receptor antagonist in the mediation of rheumatoid arthritis , 2000, Annals of the rheumatic diseases.

[46]  T. Chang.  The pharmacological basis of anti-IgE therapy , 2000, Nature Biotechnology.

[47]  S. Nakae,et al.  Development of Chronic Inflammatory Arthropathy Resembling Rheumatoid Arthritis in Interleukin 1 Receptor Antagonist–Deficient Mice , 2000, The Journal of experimental medicine.

[48]  F. Breedveld,et al.  Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis. , 1999, Journal of immunology.

[49]  H. Aihara,et al.  Intrarenal angiotensin converting enzyme inhibition in spontaneously hypertensive rats. , 1999, European journal of pharmacology.

[50]  Z. Bentwich,et al.  Active anti-interferon-alpha immunization: a European-Israeli, randomized, double-blind, placebo-controlled clinical trial in 242 HIV-1--infected patients (the EURIS study). , 1999, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[51]  R. Zinkernagel,et al.  T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[52]  A. Lage,et al.  A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: report of a pilot clinical trial. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[53]  C. Patriarca,et al.  Autoantibodies in conventional toxicity testing. , 1997, Toxicology.

[54]  R. Djukanović,et al.  The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics. , 1997, The Journal of clinical investigation.

[55]  R. Medhamurthy,et al.  Responsiveness of human male volunteers to immunization with ovine follicle stimulating hormone vaccine: results of a pilot study. , 1997, Human Reproduction.

[56]  R. Pal,et al.  Ability of an anti-luteinizing hormone-releasing hormone vaccine to inhibit gonadotropins in postmenopausal women. , 1997, Fertility and sterility.

[57]  M. V. Regenmortel,et al.  Mapping Epitope Structure and Activity: From One-Dimensional Prediction to Four-Dimensional Description of Antigenic Specificity , 1996 .

[58]  Lars Liljas,et al.  The crystal structure of bacteriophage Qβ at 3.5 å resolution , 1996 .

[59]  J. W. Smith,et al.  Interleukin 1 Trials in Cancer Patients: A Review of the Toxicity, Antitumor and Hematopoietic Effects , 1996, The oncologist.

[60]  B. Klein,et al.  Pharmacokinetic study of anti-interleukin-6 (IL-6) therapy with monoclonal antibodies: enhancement of IL-6 clearance by cocktails of anti-IL-6 antibodies. , 1995, Blood.

[61]  R. Pal,et al.  A vaccine that prevents pregnancy in women. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[62]  P. Pumpens,et al.  Recombinant RNA phage Q beta capsid particles synthesized and self-assembled in Escherichia coli. , 1993, Gene.

[63]  R. Zinkernagel,et al.  The influence of antigen organization on B cell responsiveness. , 1993, Science.

[64]  F. Finkelman,et al.  Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes. , 1993, Journal of immunology.

[65]  B. Klein,et al.  High amounts of circulating interleukin (IL)‐6 in the form of monomeric immune complexes during anti‐IL‐6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo , 1992, European journal of immunology.

[66]  C. Chothia,et al.  The structure of protein-protein recognition sites. , 1990, The Journal of biological chemistry.

[67]  M. Ho,et al.  Human and murine antibodies cross-reactive with streptococcal M protein and myosin recognize the sequence GLN-LYS-SER-LYS-GLN in M protein. , 1989, Journal of immunology.

[68]  J. Symons,et al.  CORRELATION OF PLASMA INTERLEUKIN 1 LEVELS WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS , 1988, The Lancet.

[69]  J. Thornton,et al.  Continuous and discontinuous protein antigenic determinants , 1986, Nature.

[70]  A. Deutsch,et al.  Immune complex-like disease in 23 persons following a booster dose of rabies human diploid cell vaccine. , 1986, Vaccine.

[71]  E. Hersh,et al.  Modification of human leukocyte interferon pharmacology with a monoclonal antibody. , 1985, Cancer research.

[72]  N. Bianco,et al.  Physiological aspects of circulating immune complexes in the normal population. , 1982, Clinical and experimental immunology.

[73]  H. Goldblatt,et al.  Studies on antirenin. , 1954, The American journal of physiology.

[74]  R. Rappuoli,et al.  The diphtheria and pertussis components of diphtheria-tetanus toxoids-pertussis vaccine should be genetically inactivated mutant toxins. , 2005, The Journal of infectious diseases.

[75]  G. E. Who,et al.  Preventing chronic diseases: a vital investment , 2005 .

[76]  M. Bachmann,et al.  Therapeutic vaccination for chronic diseases: a new class of drugs in sight , 2004, Nature Reviews Drug Discovery.

[77]  O. Uhlenbeck,et al.  Specific interaction between RNA phage coat proteins and RNA. , 1991, Progress in nucleic acid research and molecular biology.