Biomedical subjects

Henry E Neuman de Vegvar

Publications and source records attributed to Henry E Neuman de Vegvar.

5 recordsLinked to original sources

PubMed2006

Tolerizing DNA vaccines for autoimmune arthritis.

Current therapies for rheumatoid arthritis (RA) and other autoimmune diseases non-specifically suppress immune function, and there is great need for fundamental approaches such as antigen-specific tolerizing therapy. In this paper we describe development of antigen-specific tolerizing DNA vaccines to treat collagen-induced arthritis (CIA) in mice, and use of protein microarrays to monitor response to therapy and to identify potential additional autoimmune targets for next generation vaccines. We demonstrate that tolerizing DNA vaccines encoding type II collagen (CII) reduced the incidence and severity of CIA. Atorvastatin, a statin drug found to reduce the severity of autoimmunity, potentiated the effect of DNA vaccines encoding CII. Analysis of cytokines produced by collagen-reactive T cells derived from mice receiving tolerizing DNA encoding CII, as compared to control vaccines, revealed reduced production of the pro-inflammatory cytokines IFN-gamma and TNF-alpha. Arthritis microarray analysis demonstrated reduced spreading of autoantibody responses in mice treated with DNA encoding CII. The development of tolerizing DNA vaccines, and the use of antibody profiling to guide design of and to monitor therapeutic responses to such vaccines, represents a promising approach for the treatment of RA and other autoimmune diseases.

Animals↗

PubMed2004

Microarray profiling of antiviral antibodies for the development of diagnostics, vaccines, and therapeutics.

Multiplex analysis of antiviral antibody (Ab) responses provides a potentially powerful strategy for viral diagnosis, prognostication, and development of vaccines and prophylactic Abs. In the coming years, advancements in proteomic technologies will provide even more robust methods to characterize antiviral Ab responses. Biomedical researchers will be faced with the exciting challenge of identifying antiviral Ab specificities that correlate with improved outcomes and efficacious interventions, and translating the findings into more effective diagnostics, prophylactics, and therapeutics.

Animals↗

PubMed2003

Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis.

The diversity of autoimmune responses poses a formidable challenge to the development of antigen-specific tolerizing therapy. We developed 'myelin proteome' microarrays to profile the evolution of autoantibody responses in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Increased diversity of autoantibody responses in acute EAE predicted a more severe clinical course. Chronic EAE was associated with previously undescribed extensive intra- and intermolecular epitope spreading of autoreactive B-cell responses. Array analysis of autoantigens targeted in acute EAE was used to guide the choice of autoantigen cDNAs to be incorporated into expression plasmids so as to generate tolerizing vaccines. Tolerizing DNA vaccines encoding a greater number of array-determined myelin targets proved superior in treating established EAE and reduced epitope spreading of autoreactive B-cell responses. Proteomic monitoring of autoantibody responses provides a useful approach to monitor autoimmune disease and to develop and tailor disease- and patient-specific tolerizing DNA vaccines.

Animals↗

PubMed2003

Microarray profiling of antibody responses against simian-human immunodeficiency virus: postchallenge convergence of reactivities independent of host histocompatibility type and vaccine regimen.

We developed antigen microarrays to profile the breadth, strength, and kinetics of epitope-specific antiviral antibody responses in vaccine trials with a simian-human immunodeficiency virus (SHIV) model for human immunodeficiency virus (HIV) infection. These arrays contained 430 distinct proteins and overlapping peptides spanning the SHIV proteome. In macaques vaccinated with three different DNA and/or recombinant modified vaccinia virus Ankara (rMVA) vaccines encoding Gag-Pol or Gag-Pol-Env, these arrays distinguished vaccinated from challenged macaques, identified three novel viral epitopes, and predicted survival. Following viral challenge, anti-SHIV antibody responses ultimately converged to target eight immunodominant B-cell regions in Env regardless of vaccine regimen, host histocompatibility type, and divergent T-cell specificities. After challenge, responses to nonimmunodominant epitopes were transient, while responses to dominant epitopes were gained. These data suggest that the functional diversity of anti-SHIV B-cell responses is highly limited in the presence of persisting antigen.

Amino Acid Sequence↗

PubMed2002

Autoantigen microarrays for multiplex characterization of autoantibody responses.

We constructed miniaturized autoantigen arrays to perform large-scale multiplex characterization of autoantibody responses directed against structurally diverse autoantigens, using submicroliter quantities of clinical samples. Autoantigen microarrays were produced by attaching hundreds of proteins, peptides and other biomolecules to the surface of derivatized glass slides using a robotic arrayer. Arrays were incubated with patient serum, and spectrally resolvable fluorescent labels were used to detect autoantibody binding to specific autoantigens on the array. We describe and characterize arrays containing the major autoantigens in eight distinct human autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. This represents the first report of application of such technology to multiple human disease sera, and will enable validated detection of antibodies recognizing autoantigens including proteins, peptides, enzyme complexes, ribonucleoprotein complexes, DNA and post-translationally modified antigens. Autoantigen microarrays represent a powerful tool to study the specificity and pathogenesis of autoantibody responses, and to identify and define relevant autoantigens in human autoimmune diseases.

Animals↗