An adenovirus-vectored nasal vaccine confers rapid and sustained protection against anthrax in a single-dose regimen.

Bacillus anthracis is the causative agent of anthrax, and its spores have been developed into lethal bioweapons. To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encoding B.

Adenovirus-vectored drug-vaccine duo as a rapid-response tool for conferring seamless protection against influenza.

Few other diseases exert such a huge toll of suffering as influenza. We report here that intranasal (i.n.

Adenovirus as a carrier for the development of influenza virus-free avian influenza vaccines.

A long-sought goal during the battle against avian influenza is to develop a new generation of vaccines capable of mass immunizing humans as well as poultry (the major source of avian influenza for human infections) in a timely manner. Although administration of the currently licensed influenza vaccine is effective in eliciting protective immunity against seasonal influenza, this approach is associated with a number of insurmountable problems for preventing an avian influenza pandemic. Many of the hurdles may be eliminated by developing new avian influenza vaccines that do not require the propagation of an influenza virus during vaccine production.

Automated mass immunization of poultry: the prospect for nonreplicating human adenovirus-vectored in ovo vaccines.

Automated in ovo vaccination is an efficient method for mass immunization of poultry. Although in ovo vaccination has been used to mass immunize chickens against several infectious diseases, there are common poultry diseases for which in ovo-compatible vaccines are not commercially available. It was recently demonstrated that in ovo administration of a nonreplicating human adenovirus vector encoding an avian influenza virus hemagglutinin induced protective immunity against highly pathogenic avian influenza.

Nasal inoculation of an adenovirus vector encoding 11 tandem repeats of Abeta1-6 upregulates IL-10 expression and reduces amyloid load in a Mo/Hu APPswe PS1dE9 mouse model of Alzheimer's disease.

Background: One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amyloid beta-peptide (Abeta) in neuritic plaques and cerebral vessels. Immunization of AD mouse models with Abeta reduces Abeta deposits and improves memory and learning deficits. Because recent clinical trials of immunization with Abeta were halted due to brain inflammation that was presumably induced by a T-cell-mediated autoimmune response, vaccination modalities that elicit predominantly humoral immune responses are currently being developed.

Viral vectors for malaria vaccine development.

A workshop on viral vectors for malaria vaccine development, organized by the PATH Malaria Vaccine Initiative, was held in Bethesda, MD on October 20, 2005. Recent advancements in viral-vectored malaria vaccine development and emerging vector technologies were presented and discussed. Classic viral vectors such as poxvirus, adenovirus and alphavirus vectors have been successfully used to deliver malaria antigens.

Topical application of Escherichia coli-vectored vaccine as a simple method for eliciting protective immunity.

We report here that animals can be protected against lethal infection by Clostridium tetani cells and Bacillus anthracis spores following topical application of intact particles of live or gamma-irradiated Escherichia coli vectors overproducing tetanus and anthrax antigens, respectively. Cutaneous gammadeltaT cells were rapidly recruited to the administration site. Live E.

Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid beta-protein and GM-CSF.

Lines of experimental evidence indicate that induction of humoral immune responses in transgenic mouse models of Alzheimer disease (AD) by repeated injection of synthetic amyloid beta-protein (Abeta) is effective in prevention and clearance of deposits of Abeta aggregates in the brain of the mice. We have tested a non-injection modality whereby replication-defective adenovirus vectors encoding Abeta or the 99-amino acid carboxyl terminal fragment of Abeta precursor were intranasally administered to mice to elicit immune responses against Abeta. When mice were immunized only with the adenovirus vectors, immune responses against Abeta were negligible.

A differential proteome in tumors suppressed by an adenovirus-based skin patch vaccine encoding human carcinoembryonic antigen.

We created an anti-tumor vaccine by using adenovirus as a vector which contains a cytomegalovirus early promoter-directed human carcinoembryonic antigen gene (AdCMV-hCEA). In an attempt to develop the skin patch vaccine, we epicutaneously vaccinated Balb/c mice with AdCMV-hCEA. After nine weeks post-immunization, vaccinated mice evoked a robust antibody titer to CEA and demonstrated the capability of suppressing in vivo growth of implanted murine mammay adenocarioma cell line (JC-hCEA) tumor cells derived from a female Balb/c mouse.

Safety and immunogenicity of adenovirus-vectored nasal and epicutaneous influenza vaccines in humans.

The increasing number and density of the human population, the emergence of lethal influenza strains, and the potential use of designer influenza virus as a bioweapon, collectively highlight a critical need for more rapid production of influenza vaccines and less invasive means of delivery. We have developed a nonreplicative adenovirus-vectored influenza vaccine that can be produced without the prerequisite of growing influenza virus. This new class of vaccines can be administered as a nasal spray or skin patch by personnel without medical training.

Prospective highlights of functional skin proteomics.

Although a wide variety of protein profiles have been extensively constructed via proteomic analysis, the comprehensive proteomic profiling of the skin, which is considered to be the largest organ of the human body, is still far from complete. Our efforts to establish the functional skin proteome, a protein database describing the protein networks that underlie biological processes, has set in motion the identification and characterization of proteins expressed in the epidermis and dermis of the BALB/c mice. In this review, we will highlight various cutaneous proteins we have characterized and discuss their biological functions associated with skin distress, immunity, and cancer.

Identification of Bacillus anthracis proteins associated with germination and early outgrowth by proteomic profiling of anthrax spores.

The use of anthrax spores as a bioweapon has spurred efforts aimed at identifying key proteins expressed in Bacillus anthracis. Because spore germination and outgrowth occur prior to and are required for disease manifestations, blocking germination and early outgrowth with novel vaccines or inhibitors targeting critical B. anthracis germination and outgrowth-associated factors is a promising strategy in mitigating bioterror.

Comparative proteomic profiling of murine skin.

Mammalian skin is regularly exposed to different environmental stresses, each of which results in specific compensatory changes in protein expression that can be assessed by proteomic analysis. We have established a reference proteome map of BALB/c murine skin allowing the resolution of greater than 500 protein spots in a single two-dimensional polyacrylamide gel. Forty-four protein spots, corresponding to 28 different cutaneous proteins, were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the Mascot online database searching algorithm.