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Gaithersburg, MD, United States

The emergence of a highly pathogenic avian influenza virus H5N1 has increased the potential for a new pandemic to occur. This event highlights the necessity for developing a new generation of influenza vaccines to counteract influenza disease. These vaccines must be manufactured for mass immunization of humans in a timely manner. Poultry should be included in this policy, since persistent infected flocks are the major source of avian influenza for human infections. Recombinant adenoviral vectored H5N1 vaccines are an attractive alternative to the currently licensed influenza vaccines. This class of vaccines induces a broadly protective immunity against antigenically distinct H5N1, can be manufactured rapidly, and may allow mass immunization of human and poultry. Recombinant adenoviral vectors derived from both human and non-human adenoviruses are currently being investigated and appear promising both in nonclinical and clinical studies. This review will highlight the current status of various adenoviral vectored H5N1 vaccines and will outline novel approaches for the future. © 2012 by the authors; licensee MDPI, Basel, Switzerland. Source

Vaxin Inc | Date: 2013-12-30

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Vaxin Inc | Date: 2014-09-05

Methods and compositions are provided herein for non-invasive administration of an adenoviral vector (Ad-vector) vaccine with an adjuvant, such as a TLR3 agonist. These methods provide, for example, an increase in the immune response to the vaccine, an increase in the immunogenicity of the Ad-vector vaccine, an antigen sparing effect and improved safety with an effective protective immune response to the vaccine.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 100.00K | Year: 2007

DESCRIPTION (provided by applicant): Alzheimer disease (AD) is the most common neurodegenerative disease in the elderly. To date, no satisfactory treatment is available for AD. One of the pathological hallmarks of AD is deposits of amyloid protein (Aa) in neuritic plaques and cerebral vessels. Increasing lines of evidence support the notion that Aa and its precursor (APP) play pathogenetic roles in the etiology of AD. Overexpression of the mutant forms of APP in transgenic mice led to AD-like pathologies including amyloid plaques in the brain. Parenteral immunization of these AD mouse models with synthetic Aa prevented or reduced Aa deposits and improved their memory and learning deficits. Human clinical trials of Aa immunization, however, were halted due to brain inflammation presumably induced by T cell-mediated autoimmune responses. Recent reports of the clinical trials indicate that Aa immunization is effective in clearing Aa deposits and improving cognitive deficits in AD patients. Thus, it is crucial to find safe and effective immune therapy. Peripheral administration of antibodies against Aa also induced clearance of preexisting amyloid plaques in AD mouse models. Therefore, the development of successful therapeutic vaccines against AD is thought to depend on identification of immunization strategies that can induce potent Aa-specific Th2 immune responses without eliciting adverse effects. We produced an adenovirus-vectored vaccine which encodes a B-cell epitope of Aa. The adenovirus vaccine induced predominantly Th2 immune responses and had prophylactic effects on AD-like changes in AD model mice. Vaxin Inc. developed the proprietary AdHigh system for rapid production of replication-competent adenovirus (RCA)-free adenovirus vectors. Based upon our experimental results, we will further assess the safety and efficacy of the RCA-free adenovirus vector in treating AD model mice in the Phase I project. The Specific Aims are (1) Construction of the RCA-free adenovirus vector, (2) Determination of immune responses induced by nasal administration of the RCA-free adenovirus vector in an AD mouse model, and (3) Evaluation of the efficacy and the safety of the nasal administration of the RCA-free adenovirus vector in an AD mouse model. Therefore, this application is a necessary step toward a clinical trial of our adenovirus vectored vaccine. Primer's disease (AD) is characterized by the progressive loss of memory and cognitive functions. To date, no satisfactory treatments are available for AD. We propose to test the efficacy and safety of a RCA-free adenovirus vectored vaccine using animal models of AD in order to treat and prevent AD.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 111.80K | Year: 2006

DESCRIPTION (provided by applicant): The aim of this proposal is to develop an effective and rapid method for disrupting the poultry-to- human transmission of avian influenza by in ovo injection of flu vaccines that can be mass- administered with a mechanized injector. The hypothesis is that mass-vaccination of poultry against an outbreak of avian influenza reduces the dissemination of the virus to new flocks and consequently the risk to humans. As avian influenza gets more and more deadly, it is increasingly urgent to produce vaccines rapidly in response to an unprecedented escalation in demand. Emerging evidence suggests that poultry can be immunized en masse by in ovo administration of DMA vaccines and non-replicating adenovirus (Ad)-vectored vaccines without masking infections. Both vaccines are produced by molecular biology techniques without the requirement to propagate lethal virus strains. These studies will compare these two vaccination modalities in their potency to mobilize the immune repertoire toward a beneficial immune protection against avian influenza virus infection in chickens. In this project, efficacy of a DMA vaccine will be compared to that induced by a non-replicating Ad vector encoding the same codon-optimized A/Turkey/Wisconsin/68 hemagglutinin gene. Both vaccines will be injected into the amnion of chicken embryos. The tetradecylmaltoside surfactant will be evaluated as a gene delivery enhancer for both classes of vaccines. Hemagglutination- inhibition (HI) antibody titers against the A/Turkey/Wisconsin/68 virus will be analyzed in chickens post-hatch. Ad vectors will be generated using a new AdHigh system developed for manufacturing replication-competent Ad (RCA)-free Ad vectors at high speed and high titer. The overall goal of these experiments is to determine whether high HI antibody titers against avian influenza virus can be elicited in chickens by in ovo injection of non-replicating vectored vaccines without using the avian influenza virus itself, and thus avoiding the related biohazard of growing a deadly virus strain as well as difficulty of distinguishing the effect of vaccination from that of infection.

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