Vaccinia virus vectors: new strategies for producing recombinant vaccines.

Hruby, Dennis E.

doi:10.1128/cmr.3.2.153-170.1990

Cited by 5 publications

(6 citation statements)

References 65 publications

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“…Vaccinia virus infection through the basolateral membrane. The ability of vaccinia virus to infect most cell lines has suggested a broad cellular tropism and possibly a ubiquitously expressed viral receptor (18,29). However, the finding that vaccinia virus readily infected activated but not resting T cells suggested the presence of a specific cell surface viral receptor (9).…”

Section: Discussionmentioning

confidence: 99%

Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia

Vermeer

McHugh

Rokhlina

et al. 2007

J Virol

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Variola virus, the causative agent of smallpox, enters and exits the host via the respiratory route. To better understand the pathogenesis of poxvirus infection and its interaction with respiratory epithelia, we used vaccinia virus and examined its interaction with primary cultures of well-differentiated human airway epithelia. We found that vaccinia virus preferentially infected the epithelia through the basolateral membrane and released viral progeny across the apical membrane. Despite infection and virus production, epithelia retained tight junctions, transepithelial electrical conductance, and a steep transepithelial concentration gradient of virus, indicating integrity of the epithelial barrier. In fact, during the first four days of infection, epithelial height and cell number increased. These morphological changes and maintenance of epithelial integrity required vaccinia virus growth factor, which was released basolaterally, where it activated epidermal growth factor 1 receptors. These data suggest a complex interaction between the virus and differentiated airway epithelia; the virus preferentially enters the cells basolaterally, exits apically, and maintains epithelial integrity by stimulating growth factor receptors.The threat of bioterrorism has raised concern that smallpox could reemerge as a significant disease entity (10,21,46). The large population of unvaccinated individuals, the many immunocompromised people, and the lack of good treatments suggest that variola virus, the causative agent of smallpox, has the potential for extensive and rapid spread. Thus, there is a renewed interest in understanding poxvirus pathogenesis.Variola virus infection occurs following the inhalation of virus-laden airborne droplets (7, 12, 13a, 34). Virus replication within the lung and lymphoid system is followed by viremia (16,41,57). Patients remain asymptomatic during the 7-to 17-daylong incubation period, after which symptoms develop, including fever, malaise, and head and body aches, followed by oropharyngeal lesions and skin rash 2 to 4 days later. Sloughing of oropharyngeal lesions and respiratory tract release discharge infectious viral particles into the air, perpetuating human-tohuman spread (14, 27, 52). The high mortality rate associated with smallpox results from the overwhelming toxemia leading to respiratory and/or cardiac failure. These observations indicate that infection involves viral entry and exit through the oropharyngeal-respiratory route and suggest that the airways may play a key role in the viral life cycle.Because of the risks of experiments using variola virus, the limitations and difficulties associated with studies of nonhuman animals, and insufficient clinical information from humans, much of our knowledge about the interaction between poxvirus and the host has come from studies using vaccinia virus and cultured cells. Vaccinia virus is the orthopoxvirus used for immunization against smallpox, and it is widely substituted for variola virus in the investigation of poxvirus biology (20,28,4...

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Section: Discussionmentioning

confidence: 99%

Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia

Vermeer

McHugh

Rokhlina

et al. 2007

J Virol

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“…Over 70 people became ill during this outbreak [28]. Another more chilling scenario is the possibility that a laboratory strain of vaccinia virus or cowpox virus could be genetically engineered to produce a toxin to convert it into a potent pathogen [29]. Fortunately, orthopoxviruses are highly related at the DNA level (e.g.…”

Section: Smallpox As a Bw Pathogenmentioning

confidence: 99%

Commensal bacteria as a novel delivery system for subunit vaccines directed against agents of bioterrorism

Wilson

Hruby

2005

Advanced Drug Delivery Reviews

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Following the anthrax attacks of 2001 and the recent SARS outbreak, concerns about emerging and re-emerging infectious diseases have catalyzed a renewed interest in developing new vaccination strategies that provide rapid and flexible response options to future threats. Because the probability of encountering one of these exotic agents is unknown, it is essential that new vaccine formulations employ methods that provide effective protection and extremely good safety profiles if they are to be used by either military or civilian populations. One approach, which potentially satisfies these criteria, is the use of live recombinant Gram-positive commensal bacteria as expression vectors. This review provides an overview of the system, its advantages and limitations, and details an example of how Gram-positive commensal bacteria are being developed as a fifth generation vaccine against a Class A biowarfare pathogen, namely smallpox.

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“…Vaccines consisting of inactivated virus or soluble proteins do not induce cytotoxic responses because the antigens involved are not able to enter the cell cytoplasm to gain access to the endogenous class I processing pathway [161]. Strategies that can potentially overcome this problem include the use of live viral vectors [162][163][164], ISCOM [165][166][167] and liposome [168,169] based approaches and DNA vaccines [170]. Each of these techniques lead to transport into or expression of antigen within the cytoplasm that can then enter the class I processing pathway.…”

Section: Chemoselective Ligation As a Means Of Assembling Epitope Basmentioning

confidence: 99%

Dissecting the role of peptides in the immune response: theory, practice and the application to vaccine design

Purcell

Zeng

Mifsud

et al. 2003

Journal of Peptide Science

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Analytical biochemistry and synthetic peptide based chemistry have helped to reveal the pivotal role that peptides play in determining the specificity, magnitude and quality of both humoral (antibody) and cellular (cytotoxic and helper T cell) immune responses. In addition, peptide based technologies are now at the forefront of vaccine design and medical diagnostics. The chemical technologies used to assemble peptides into immunogenic structures have made great strides over the past decade and assembly of highly pure peptides which can be incorporated into high molecular weight species, multimeric and even branched structures together with non-peptidic material is now routine. These structures have a wide range of applications in designer vaccines and diagnostic reagents. Thus the tools of the peptide chemist are exquisitely placed to answer questions about immune recognition and along the way to provide us with new and improved vaccines and diagnostics. specificity of immune responses, it was not until the solution of the three dimensional structure of a complex between an antigenic fragment and a cell surface receptor responsible for displaying the peptide to immune effector cells, that the pivotal role of peptides in directing the T cell response was fully appreciated. The structure of a class I human leukocyte antigen (HLA) molecule revealed for the first time the unique structure of the receptor's antigen binding cleft and the presence of electron density within the cleft [1,2] indicated the presence of a short antigen-derived peptide that was the focus of antigen-specific T cell receptors present on the

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Vaccinia virus vectors: new strategies for producing recombinant vaccines.

Cited by 5 publications

References 65 publications

Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia

Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia

Commensal bacteria as a novel delivery system for subunit vaccines directed against agents of bioterrorism

Dissecting the role of peptides in the immune response: theory, practice and the application to vaccine design

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