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SEATTLE, WA, United States

Clegg C.H.,Tria Bioscience Corporation | Rininger J.A.,CaroGen Corporation | Baldwin S.L.,Infectious Disease Research Institute
Expert Review of Vaccines | Year: 2013

H5N1 is a highly pathogenic avian influenza virus that can cause severe disease and death in humans. H5N1 is spreading rapidly in bird populations and there is great concern that this virus will begin to transmit between people and cause a global crisis. Vaccines are the cornerstone strategy for combating avian influenza but there are complex challenges for pandemic preparedness including the unpredictability of the vaccine target and the manufacturing requirement for rapid deployment. The less-than-optimal response against the 2009 H1N1 pandemic unmasked the limitations associated with influenza vaccine production and in 2010, the President's Council of Advisors on Science and Technology re-emphasized the need for new recombinant-based vaccines and adjuvants that can shorten production cycles, maximize immunogenicity and satisfy global demand. In this article, the authors review the efforts spent in developing an effective vaccine for H5N1 influenza and summarize clinical studies that highlight the progress made to date. © 2013 Informa UK Ltd. Source

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 352.84K | Year: 2012

DESCRIPTION (provided by applicant): Tobacco smoke is the primary cause of lung cancer, cardiovascular disease and premature death, with nearly 5 million people dying each year. Treatments that prevent smoking will have a major impact on global health andare attractive products for commercial development. Nicotine vaccines and antibodies represent an important strategy for preventing nicotine from reaching the brain, although current clinical-stage vaccines are ineffective and for most people the antibodyresponse is weak and short-lived. The challenge of inducing long- lasting antibodies titers requires a better method for presenting nicotine to the immune system. We hypothesize that targeted nicotine delivery to dendritic cells using agonistic mAbs to CD40 combined with a TLR4-based adjuvant will stimulate a superior antibody response. We will modify the rat anti-mouse CD40 mAb 1C10 for studies in mice and optimize its conjugation with derivatized nicotine. Mice will be vaccinated with ?CD40nic formulatedwith the TLR4-activating adjuvant GLA-SE. Anti-nicotine antibody titers will be benchmarked against mice vaccinated with a traditional vaccine, nicotine-KLH + alum. Vaccine potency will be determined using quantitative measures of antibody function including nicotine sequestration in blood and prevention of a nicotine abstinence response. Phase I SBIR funding will establish proof-of-concept in a relevant model and provide the justification for subsequent IND-enabling studies that will bring an innovative vaccine for smoking cessation into the clinic. PUBLIC HEALTH RELEVANCE: Tobacco smoke is the primary cause of lung cancer, cardiovascular disease and premature death. There is a strong unmet need for an effective aid to smoking cessation. To halt the addictive effects of nicotine and increase the success rate for smoking cessation, we have designed a novel vaccine that will prevent nicotine from crossing the blood-brain barrier.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 579.38K | Year: 2013

DESCRIPTION (provided by applicant): Allergy is a major cause of illness and disability with an estimated 40-50 million people afflicted in the US alone. AIT provides long-term benefits for the patient and its need for optimization creates a compelling business opportunity. There is a very strong rationale to develop GLA for allergy based on its superior drug profile to MPL, a related TLR4 agonist that accelerates desensitization in people. Our preclinical development plan is easy to execute given the vaccines simple design, and it is very low risk given GLA's safety record in toxicology studies and current clinical programs. This Phase I SBIR will clarify the pharmacology and product profile for the IND. The goal is to confirm that GLA will augment the immunogenicity of multiple allergens and verify that it can accelerate desensitization in a compelling manner. The intention is to generate three potential vaccine candidates for evaluation by an external advisory board. In addition to new innovative allergy products, this work will help us understand the mechanisms of IgE-mediated disease and how to effectively cure allergy through tolerance induction. TRIA has the resources and experience to complete the task. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Allergy is a major cause of illness and disability with an estimated 40-50 million people afflicted in the US alone. Allergy immunotherapy cures some patients although it is underutilized and suffers from poor compliance. Adjuvants can be mixed with allergy vaccines to accelerate tolerance with fewer injections and no adverse reactions.

Clegg C.H.,Tria Bioscience Corporation | Roque R.,Tria Bioscience Corporation | Perrone L.A.,Tria Bioscience Corporation | Perrone L.A.,University of Washington | And 3 more authors.
PLoS ONE | Year: 2014

The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development. © 2014 Clegg et al. Source

Miller K.D.,Tria Bioscience Corporation | Miller K.D.,Affinogen Bioscience LLC | Roque R.,Tria Bioscience Corporation | Clegg C.H.,Tria Bioscience Corporation
PLoS ONE | Year: 2014

Tobacco addiction represents one of the largest public health problems in the world and is the leading cause of cancer and heart disease, resulting in millions of deaths a year. Vaccines for smoking cessation have shown considerable promise in preclinical models, although functional antibody responses induced in humans are only modestly effective in preventing nicotine entry into the brain. The challenge in generating serum antibodies with a large nicotine binding capacity is made difficult by the fact that this drug is non-immunogenic and must be conjugated as a hapten to a protein carrier. To circumvent the limitations of traditional carriers like keyhole limpet hemocyanin (KLH), we have synthesized a short trimeric coiled-coil peptide (TCC) that creates a series of B and T cell epitopes with uniform stoichiometry and high density. Here we compared the relative activities of a TCC-nic vaccine and two control KLH-nic vaccines using Alum as an adjuvant or GLA-SE, which contains a synthetic TLR4 agonist formulated in a stable oil-in-water emulsion. The results showed that the TCC's high hapten density correlated with a better immune response in mice as measured by anti-nicotine Ab titer, affinity, and specificity, and was responsible for a reduction in anti-carrier immunogenicity. The Ab responses achieved with this synthetic vaccine resulted in a nicotine binding capacity in serum that could prevent >90% of a nicotine dose equivalent to three smoked cigarettes (0.05 mg/kg) from reaching the brain. © 2014 Miller et al. Source

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