Other

Swey-shen Alexchen

Swey-Shen Chen

Zhong Yu Chen

Yong-Min Yang

Theresa J Barankiewicz

The embodiment of the invention is to conformationally constrain neutralizing B cell epitopes of CoV-2, CoV-n B cell epitopes of the open reading frame proteins, including the membrane S protein, constrained by protein scaffolds, including camelid VHH nanobody in order to elicit neutralizing and blocking antibodies against viral infection. B cell epitopes are molecularly evolved by ribosome display to preempt emerging viral B cell epitopes. Moreover, CTL epitopes are designed from the open reading frame protein for eliciting cell mediated viral protection. Furthermore, mRNA vaccines are prepared for eliciting protective immunity and prevent cytokine storms.

CoV-2 (CoV-n) antibody neutralizing and CTL vaccines using protein scaffolds and molecular evolution

The embodiment of the invention is to enable universal non-classical MHC I peptide vaccines restricted to HLA-E, HLA-F and HLA-G. An algorithm was develop to predict HLA-E binding immunogenic or suppressorgenic peptides of the autologous origins, e.g., autoantigens, inflammatory antigens, IgE and cancer antigens, and of the microbial origins. Thus, the embodiment of the invention is to load the antigenic peptides of medical and therapeutic importance onto the non-polymorphic HLA-E, HLA-F, and HLA-G culminating in universal vaccines, bypassing highly polymorphic classical MHC I, e.g., HLA-A, HLA-B and HLA-C pathways, in order to treat autoimmune diseases, allergy, inflammatory diseases, cancers, and infectious diseases for all human population. Derlin-1 and UL40 pathways are utilized to enable antigen presentation and vaccine efficacies in the non-classical MHC I pathways.

Universal non-classical MHC I vaccines: HLA-E-restricted antigenic peptides as universal vaccines to treat allergy, inflammation, autoimmune and infectious diseases, and cancers

Galectin-3 is a pro-inflammatory molecule functioning as a cytokine hub, and also regulates unfolded protein responses (UPR) and ER stress. Thus, galectin-3 serves as a target for ameliorating inflammatory diseases such as allergic inflammation and diabetic inflammation and insulin resistance. RNA interference of endogenous galectin-3 expression, upregulates IL-12, IL-10 while downregulating IL-23 production, which offers protection against allergic inflammation. In addition, endogenous galectin-3 knockdown causes upregulation of XBP1, alleviating ER stress. Together, upregulated XBP1 and IL-10 offer protection against obesity-induced inflammation. Therefore, the embodiment of the invention resides in RNA interference of endogenous galectin-3 in appropriate cell types in order to rectify allergic and/or diabetic inflammation.

RNA interference of galectin-3 expression and methods of use thereof

A method is disclosed wherein an antigenic B-cell epitope is discovered by in vitro transcription and translation of pre-determined sequence on thermostable protein scaffolds detected by antibodies to a native protein. Immune reactivities of IgE B-cell epitopes from pre-determined IgE sequences from the constant region, engaged in binding to high affinity IgE Fc receptors, placed in a loop of green fluorescent protein (GFP) were shown immuno-reactive with anti-IgE. Moreover, the antigenic B-cell epitope can be further optimized by molecular evolution, selected by conformer antibody and receptor on solid phase via ribosome display. Alternatively, a random aptameric antigenic sequence inserted into a loop of the protein scaffold, mimicking a pre-determined sequence of a native protein, can be selected by solid phase conformer antibody and receptor via ribosome display. High affinity binding of B-cell epitopes selected from the random aptameric library with antibodies to native pre-determined B-cell epitope of a native protein can be optimized by molecular evolution with error-prone RT-PCR by ribosome display.

Aptameric IgE peptides in a protein scaffold as an allergy vaccine

The present invention concerns the prophylaxis or therapy of immunoglobulin E-mediated disease conditions. The present invention discloses methods for identifying peptides that induce a cytotoxic T-lymphocyte response against immunoglobulin E. The present invention further discloses compositions that are able to elicit in a mammal a cytotoxic T-lymphocyte response to naturally processed and presented immunoglobulin E peptides, and methods for their use.

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San Diego, CA, United States of America

Swey-Shen Chen