Modified Vaccination Technique for Prophylactic and Therapeutic Applications to Combat Endogenous Antigen–Induced Disorders

Cole, Chad; Barabas, A. Z.; Graeff, Richard; Lafrenière, René; Weir, D. M.

doi:10.1111/j.1365-3083.2009.02360.x

Cited by 6 publications

(4 citation statements)

References 78 publications

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“…The aim is to prevent and/or treat the disease by introducing the target ag (ag specific downregulation of the immune response) in such a way that it evokes a specific IgM aab response against the target ag [56,67,95,117,118] (Figures 6 and 7). Such cross-reactive aabs can assist in the removal of both modified and native nephritogenic aags from the system that are responsible for producing pathogenic rarKF3 ag IgG aabs which in turn cause the autoimmune disease and ICGN.…”

Section: Resultsmentioning

confidence: 99%

Immunopathological events initiated and maintained by pathogenic IgG autoantibodies in an experimental autoimmune kidney disease

et al. 2012

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The experimental models of Heymann nephritis (HN) and slowly progressive Heymann nephritis (SPHN) give us rare opportunities to investigate the etiologies and pathogenesis of two immunopathological processes in rats leading to: (1) autoimmune disease, where the autoimmune disease HN and SPHN is initiated and maintained by cross-reactive pathogenic IgG autoantibodies (aabs) directed against the renal proximal convoluted tubules' brush border (BB) cells - where the nephritogenic antigen (ag) is produced and localized - damaging and releasing BB associated nephritogenic ag into the circulation which in turn contributes to continuation of the autoimmune disease; and (2) immune complex glomerulonephritis, where the glomerular injury is initiated, proceeding into a chronic progressive disease by depositing immune complexes (ICs) - made up of a glomerular epithelial cell produced endogenous nephritogenic ag and the developing pathogenic IgG aab directed against the nephritogenic ag, and complement components - on the epithelial side of the glomerular basement membrane. We also observed how the normally functioning immune system is able to avert autoimmune disease developments by circulating specific non-pathogenic IgM aabs clearing the system of intracytoplasmic ags released from cells at the end of their life spans or following damage by toxic agents. We also described how an autoimmune disease SPHN can be prevented and when present terminated by the implementation of a new vaccination technique we have developed and call modified vaccination technique. By increasing the specific IgM aab production against the native nephritogenic ag - by injecting ICs made up of: [nephritogenic ag X homologous anti-nephritogenic ag IgM ab] in slight ag excess into SPHN rats - pathogenic IgG aab producing native and modified nephritogenic ags were removed from the circulation and termination of the autoimmune disease causing immune events was achieved. Even though HN and SPHN are not well-known disease models, their studies are important because the etiologies and pathogenesis of two conditions - that can also occur in humans, namely autoimmune diseases and membranous glomerulonephritis - can be simultaneously investigated.

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Section: Resultsmentioning

confidence: 99%

Immunopathological events initiated and maintained by pathogenic IgG autoantibodies in an experimental autoimmune kidney disease

et al. 2012

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“…acceleration/downregulation of immune responses against a self ag -as it occurs in an autoimmune disease -has not been achieved by others to date, using specifically formulated ICs, except by us [1,43,44,[57][58][59].…”

Section: Discussionmentioning

confidence: 99%

“…We firmly believe that the MVT that we have developed [1,[42][43][44]the third method of immunizing -will achieve prevention/ termination of autoimmune disorders (i.e., autoimmune disease and cancer).…”

Section: Discussionmentioning

confidence: 99%

“…The vaccination technique we have developed and call MVT is able to prevent and when present terminate an experimental autoimmune kidney disease called SPHN [1,15,[38][39][40][41][42][43]. The MVT is the third vaccination method after active and passive immunizations; and the only one which is able to initiate preventative and therapeutic responses.…”

Section: Mvt For the Prevention And When Present Termination Of An Exmentioning

confidence: 99%

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Modified self-antigen Caused Autoimmune Disease and its Reversal by a new Vaccination Technique

Barabas

Cole²,

Lafrenière³

et al. 2014

Immunome Res

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Autoimmunity represents four possible aspects of immune responses against self-components. Two of the immune responses are beneficial and two are not. We are most familiar with those aspects of autoimmunity, which are harmful to the individual and cause disease, such as they are manifested in autoimmune diseases. While the study of autoimmune diseases are important, it is equally important to know the entire spectrum of autoimmunity in order to fully understand the etiological, physiological, pathological etc. aspects of immune responses that are harmful and/or beneficial. Only by fully understanding the entire spectrum can we design appropriate interventions for treating mishaps, which can occur. Since, most of the immune events, which cause autoimmune disorders, are not yet fully unravelled, autoimmune diseases are treated non-specifically e.g. with immunosuppressive agents.One the beneficial aspects of autoimmunity is manifested in the clearance of native and modified cellular breakdown products by specific non-pathogenic IgM autoantibodies; and the other beneficial aspect manifests in the recognition and elimination of emerging cancer cells. Without these beneficial aspects of autoimmunity, life as we know could not exist.There are two harmful aspects of autoimmunity as well that manifest in autoimmune disorders: autoimmune diseases and cancer.In recent years, Barabas and colleagues have developed a new way of vaccinating that allows prevention and when present termination of an experimental autoimmune kidney disease. It is believed that the new vaccination technique with appropriate modifications will be applicable for many of the presently drug only treatable endogenous disorders, such as autoimmune diseases and cancer.

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Regaining Tolerance to a Self-antigen by the Modified Vaccination Technique

Barabas

Cole

Lafrenière

et al. 2013

Clinic Rev Allerg Immunol

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Autoimmune diseases are initiated and maintained by complex immunopathological processes in environmental and genetic factor predisposed patients. In certain autoimmune diseases, the etiologies and pathogenesis of the conditions are quite well understood; yet in others, controversy surrounds as to why and how auto-injurious processes start. Clinical and laboratory examinations reasonably well define the state of progression/remission of an autoimmune disease and allow treatment according to observed findings. However, none of the presently employed treatment options are specific. In fact, they are all nonspecific in their actions and have undesirable side effects. Over the years, experiments carried out in animals have shed light on the complex immunopathological processes which contribute to disease development and progression. At least one experimental autoimmune kidney disease-which we shall describe-helps to understand how pathogenic autoimmune responses can be terminated specifically, without side effects. Since the new vaccination method-that we call modified vaccination technique-was successfully implemented in an experimental autoimmune disease model called slowly progressive Heymann nephritis for the termination of pathogenic immune responses by a target antigen-specific treatment modality, we shall highlight its use in providing insight to physicians and autoimmunologists for its future implementation in human autoimmune diseases.

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Modified Vaccination Technique for Prophylactic and Therapeutic Applications to Combat Endogenous Antigen–Induced Disorders

Cited by 6 publications

References 78 publications

Immunopathological events initiated and maintained by pathogenic IgG autoantibodies in an experimental autoimmune kidney disease

Immunopathological events initiated and maintained by pathogenic IgG autoantibodies in an experimental autoimmune kidney disease

Modified self-antigen Caused Autoimmune Disease and its Reversal by a new Vaccination Technique

Regaining Tolerance to a Self-antigen by the Modified Vaccination Technique

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