Obesity vaccines

The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight-reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 (GLP-1) highlights the therapeutic potential of gut-derived signals acting via non-physiological mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage GI signals in order to treat obesity.

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“…Other approaches include GOAT inhibition, ghrelin receptor antagonists and immune mediated ghrelin inactivation 72,73 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Monteiro

Batterham

2017

Gastroenterology

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“…Recently, the vaccines for metabolic diseases have made considerable progress, particularly in the treatment of dyslipidemia, atherosclerosis, diabetes mellitus and hypertension, but comprehensive studies are required before any clinical applications [70]. Since T2DM is a multifactorial disorder, T2DM therapeutic-vaccine has been designed to predict obesity protein antigens [71]. Such vaccine targets include adipose tissue antigens, somatostatin, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin [71].…”

Section: Discussionmentioning

confidence: 99%

“…Since T2DM is a multifactorial disorder, T2DM therapeutic-vaccine has been designed to predict obesity protein antigens [71]. Such vaccine targets include adipose tissue antigens, somatostatin, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin [71]. In the studies of Zhang et al, 2018 and Zha et al, 2016 reported that cytokine L-1ß is a key proinflammatory substance in T2DM pathogenesis and has shown a reduction in weight gain, improved glucose tolerance and insulin sensitivity, and a lower β-cell loss in their vaccine with predicted peptide epitopes [55,72].…”

Section: Discussionmentioning

confidence: 99%

Polyvalent therapeutic vaccine for type 2 diabetes mellitus: Immunoinformatics approach to study co-stimulation of cytokines and GLUT1 receptors

Muhammad

Ashfaq

Zafar

et al. 2020

BMC Mol and Cell Biol

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Background: Type 2 diabetes mellitus (T2DM) is a worldwide disease that have an impact on individuals of all ages causing micro and macro vascular impairments due to hyperglycemic internal environment. For ultimate treatment to cure T2DM, association of diabetes with immune components provides a strong basis for immunotherapies and vaccines developments that could stimulate the immune cells to minimize the insulin resistance and initiate gluconeogenesis through an insulin independent route. Methodology: Immunoinformatics based approach was used to design a polyvalent vaccine for T2DM that involved data accession, antigenicity analysis, T-cell epitopes prediction, conservation and proteasomal evaluation, functional annotation, interactomic and in silico binding affinity analysis. Results: We found the binding affinity of antigenic peptides with major histocompatibility complex (MHC) Class-I molecules for immune activation to control T2DM. We found 13-epitopes of 9 amino acid residues for multiple alleles of MHC class-I bears significant binding affinity. The downstream signaling resulted by T-cell activation is directly regulated by the molecular weight, amino acid properties and affinity of these epitopes. Each epitope has important percentile rank with significant ANN IC 50 values. These high score potential epitopes were linked using AAY, EAAAK linkers and HBHA adjuvant to generate T-cell polyvalent vaccine with a molecular weight of 35.6 kDa containing 322 amino acids residues. In silico analysis of polyvalent construct showed the significant binding affinity (− 15.34 Kcal/mol) with MHC Class-I. This interaction would help to understand our hypothesis, potential activation of T-cells and stimulatory factor of cytokines and GLUT1 receptors. Conclusion: Our system-level immunoinformatics approach is suitable for designing potential polyvalent therapeutic vaccine candidates for T2DM by reducing hyperglycemia and enhancing metabolic activities through the immune system.

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“…Diet and physical exercise are the main ways to attain the obesity management; however, lifestyle manifestation fails to continue lifelong for some patients; therefore, many patients consider antiobesity vaccines as an alternative choice. There are mainly 4 targets for obesity vaccines now, including adipose tissue antigens, somatostatin, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin [ 63 ]. Among these vaccines, only adipose tissue antigens were tested on human.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Development of Vaccines for Diabetes, Hypertension, and Atherosclerosis

Meng

2018

Journal of Diabetes Research

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Vaccines are commonly used in the prevention of infectious diseases. The basic principle of vaccination is to use specific antigens, endogenous or exogenous to stimulate immunity against the specific antigens or cells producing them. Autoantigen or oligo vaccination has been used for disease animal models. More recently humanized monoclonal antibodies have been successfully used for the treatment of neoplastic disorders or familial hypercholesterolemia. Humanized monoclonal antibody therapy needs repeated injection, and the therapy is expensive. Therapeutic vaccination can lead to persistent immunized or immune tolerant against the therapeutic molecule(s) or site. However, immunization against those endogenous substances may also elicit persistent autoimmune reaction or destruction that do harm to health. Therefore, rigorous studies are needed before any clinical application. In this review, we briefly reviewed vaccines used in protection against common metabolic diseases including atherosclerosis, hypertension, and diabetes mellitus.

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Obesity vaccines

Cited by 17 publications

References 83 publications

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Polyvalent therapeutic vaccine for type 2 diabetes mellitus: Immunoinformatics approach to study co-stimulation of cytokines and GLUT1 receptors

Recent Advances in the Development of Vaccines for Diabetes, Hypertension, and Atherosclerosis

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