Poly ICLC

The researchers’ vaccine is a combination of an antibody against the receptor-binding domain of the spike protein on the SARS-CoV-2 virus and an adjuvant called poly(I:C). What if the COVID-19 vaccine could be a simple drop under the tongue instead of a shot in the arm? That's the result researchers from Japan’s Intelligence & Technology Lab Inc. and the Biomedical Institute of NPO Primate Agora are hoping for. Results of a study published Sept. 13 in Biology Methods and Protocols described how they developed a protein-based COVID vaccine for delivery under the tongue, or sublingually. When they tested it in primates, the animals produced antibodies against COVID without side effects. The researchers’ vaccine is a combination of an antibody against the receptor-binding domain of the spike protein on the SARS-CoV-2 virus and an adjuvant called poly(I:C), a synthetic double-stranded RNA that binds to genes associated with viral infection. It activates a subset of immune cells called antigen-presenting cells that initiate the adaptive immune response by displaying captured antigens to B and T cells, which then target the invader. Despite being a “potent” adjuvant, the researchers wrote, poly(I:C) hasn’t been approved yet for use in vaccines but is used in oncology as a complement to immunotherapy. Some studies in mice have shown that the compound increases levels of proinflammatory cytokines when administered via the nose, which raises the risk of side effects like pain, fever and swelling. Perhaps a different route of administration would temper the potential for adverse effects, the scientists reasoned. The primates received three vaccinations to start, administered four weeks apart. A booster dose was given 15 weeks after the final round in the primary series. The scientists also included a control group of three primates. After the booster dose, the team analyzed the amount and type of antibodies found in fluids from the monkeys’ mouths. They observed a desirable dose-dependent increase in IgA antibodies, “guardians of the oral and nasopharyngeal galaxy” that prevent the virus from attaching to cells in the mucosa. What’s more, they didn’t detect any obvious side effects nor did they see an increase in IgE antibodies, which are associated with an allergic response. It’s not yet clear how efficacious the vaccine is against COVID-19 nor how long protection might endure. The researchers are currently conducting additional studies to address these questions, looking at changes in markers of gene expression to better quantify how well it works. Results from other research groups might offer a preview. ImmunityBio and NantKwest launched a phase 1b trial of sublingual, subcutaneous and oral versions of their COVID-19 vaccine in March 2021. The primary completion date was set for January 2023, though there haven’t been any updates since. Meanwhile, in March, researchers at the University of California, Los Angeles reported that their universal oral COVID-19 vaccine prevented severe illness in hamsters, one of the most vulnerable models to the disease. More progress is being made on intranasal vaccines. The furthest along is a live attenuated vaccine from Codagenix, which is currently being tested in Africa in a phase 3 trial backed by the World Health Organization. Startup Blue Lake Biotechnology reported phase 1 results in February showing that its intranasal vaccine reduced the risk of contracting COVID by 83% in people who received it as a booster dose. It’s now undergoing a phase 2 trial.

Data continues to demonstrate the broader potential of ‘1104 to avoid and reduce inflammation in multiple models of disease, including allergy and beyond NEW ORLEANS and CAMBRIDGE, UK,, May 22, 2023 (GLOBE NEWSWIRE) -- Revolo Biotherapeutics (“Revolo” or the “Company”), a company developing therapies that reset the immune system to achieve superior long-term remission for patients with autoimmune and allergic diseases, today announced new preclinical data discussed in a poster presentation at the American Thoracic Society (ATS) 2023 International Conference. The poster showcases the ability of its immune-resetting drug candidate ‘1104 to inhibit and reduce lung inflammation without immunosuppression in a new model of acute respiratory distress syndrome (ARDS) associated with influenza infection. “We are pleased with these new results which showcase the potential of ‘1104 to modulate the inflammatory response in the lung in models beyond our lead allergic disease indications,” said Jonathan Rigby, Chief Executive Officer of Revolo. “The data continues to highlight the unique mechanism of action (MOA) of ‘1104, acting ahead of the inflammatory cascade to reset the immune system. As we build on the positive Phase 2a trial data of ‘1104 in eosinophilic esophagitis (EoE) and prepare to release data from our second Phase 2a study of ‘1104 in allergic disease, we continue to evaluate additional potential indications that could benefit from ‘1104’s unique MOA.” In this model, Mice treated with ‘1104 had significantly reduced inflammatory infiltration in the lung by neutrophils, macrophages, and lymphocytes compared to those treated with dexamethasone.Prophylactic and therapeutic dosing of ‘1104 resulted in a dose-dependent suppression of relevant pro-inflammatory cytokines and chemokines (TNF-a, interleukin 1β (IL-1β), IL-6, IL-17, MCP-1, and MIP-1a), usually elevated in ARDS-associated viral infection.Neither ‘1104 nor the positive control had a significant effect on viral load in lung tissue, indicating that ‘1104 can modulate the immune inflammatory response without causing immunosuppression. As part of the study, mice were infected with influenza A virus (IAV). Three days after infection, animals received either PBS (negative control) or 30µg of polyinosinic-polycytidylic acid (poly I:C) to exacerbate influenza-induced lung inflammation. Mice were treated with ‘1104 (80 or 800 µg/Kg) or PBS 15 minutes before and 24 hours after poly I:C or with dexamethasone at 10mg/kg (treatment control), 1 hour before and 24 hours after the poly I:C challenge. At 48 hours after the poly I:C challenge, bronchoalveolar lavage fluid was collected to conduct differential cell counts and to measure cytokines. Lung tissue was also collected to determine the viral load. About ‘1104‘1104 is a first-in-class peptide derived from a natural immune-regulatory protein, mTB Chaperonin 60.1 that is involved in resetting the immune system. Revolo Bio has recently advanced ‘1104 through two Phase 2a trials: one in patients with eosinophilic esophagitis (EoE) and one in patients with allergen sensitivity, while exploring its potential for other allergic diseases. Revolo BiotherapeuticsRevolo Biotherapeutics is developing therapies that reset the immune system to achieve superior long-term remission for patients with autoimmune and allergic disease, without the immune system suppression seen with current therapies. Its two drug candidates, ‘1805 and ‘1104, a protein and a peptide respectively, reset the immune system to prevent the chronic pro-inflammatory immune response that results in autoimmune or allergic disease. ‘1805 is a modified analogue of a key protein in immune function nearing initiation of a second Phase 2b clinical trial for moderate-to-severe rheumatoid arthritis and a Phase 2a clinical trial for an additional autoimmune indication. The disease-agnostic mechanism of action of Revolo Biotherapeutic’s assets provides a potential platform for the development of treatments for multiple autoimmune and allergic diseases. For further information, please visit www.revolobio.com. Company ContactMarylyn Rigby, VP Investor Relations & Marketing mrigby@revolobio.com Media Contact Monica Rouco Molina, Ph.D.LifeSci Communications+1-929-469-3850mroucomolina@lifescicomms.com