Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

Bowick, Gavin C.; Barrett, Alan D.T.

doi:10.1155/2010/236528

Cited by 11 publications

(12 citation statements)

References 76 publications

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“…Mutations, deletions, segments and signaling Gavin C. Bowick [1][2][3][4], * and Alexander J. McAuley 1,4 1 Department of Microbiology & Immunology; 2 Center for Biodefense and Emerging Infectious Diseases; 3 Sealy Center for Vaccine Development; 4 Institute for Human Infections & Immunity; University of Texas Medical Branch; Galveston, TX USA and threaten new populations. Emerging infections present myriad challenges for vaccine design.…”

Section: Vaccine and Adjuvant Design For Emerging Virusesmentioning

confidence: 99%

“…Emerging infections present myriad challenges for vaccine design. 1 However, historically, infections we now refer to as emerging or biothreat agents have been the targets of successful vaccines including yellow fever and, perhaps the most striking example, smallpox, which has been eradicated from the wild thanks to a coordinated worldwide vaccination campaign. A summary of vaccines against emerging viruses can be found in reference 1; an overview of the potential limitations of some of the novel vaccine development strategies discussed in this commentary is shown in Table 1.…”

Section: Vaccine and Adjuvant Design For Emerging Virusesmentioning

confidence: 99%

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Vaccine and adjuvant design for emerging viruses

Bowick

McAuley

2011

Bioengineered Bugs

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Vaccination is currently the most effective strategy to medically control viral diseases. However, developing vaccines is a long and expensive process, and traditional methods, such as attenuating wild-type viruses by serial passage, may not be suitable for all viruses and may lead to vaccine safety considerations, particularly in the case of the vaccination of particular patient groups, such as the immunocompromised and the elderly. In particular, developing vaccines against emerging viral pathogens adds a further level of complexity, as they may only be administered to small groups of people or only in response to a specific event or threat, limiting our ability to study and evaluate responses. In this commentary, we discuss how novel techniques may be used to engineer a new generation of vaccine candidates as we move toward a more targeted vaccine design strategy, driven by our understanding of the mechanisms of viral pathogenesis, attenuation and the signaling events which are required to develop a lasting, protective immunity. We will also briefly discuss the potential future role of vaccine adjuvants, which could be used to bridge the gap between vaccine safety, and lasting immunity from a single vaccination.

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Section: Vaccine and Adjuvant Design For Emerging Virusesmentioning

confidence: 99%

Section: Vaccine and Adjuvant Design For Emerging Virusesmentioning

confidence: 99%

Vaccine and adjuvant design for emerging viruses

Bowick

McAuley

2011

Bioengineered Bugs

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“…The filoviruses, CCHFV, and LASV require the highest level of laboratory containment (containment level 4 or biosafety level 4), however, few such facilities are present in resource-poor endemic countries [ 2 ]. The worldwide threat of VHF agents to the public health, as well as to veterinary and agricultural communities, is increasingly recognized, as is the possibility of the accidental or malicious release of some of these viruses as agents of bioterror [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

et al. 2015

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CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

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“…We hypothesize that similar computational characterization of pathogen biology, pathogenesis and hostresponse genomic pathways across multiple infectious agents can enable systematic identification of targets of intervention that will impact multiple pathogens in a similar manner, and thus serve as broad-spectrum drug targets that can be modulated by novel or repurposed therapeutic modalities 6,7 . To test this hypothesis, we extended our approach to identify and predict host-based pathway mechanisms that, once validated, would have a beneficial therapeutic effect against a given pathogen.…”

Section: Introductionmentioning

confidence: 99%

Predictive Systems Biology Approach to Broad-Spectrum, Host-Directed Drug Target Discovery in Infectious Diseases

et al. 2012

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Knowledge of immune system and host-pathogen pathways can inform development of targeted therapies and molecular diagnostics based on a mechanistic understanding of disease pathogenesis and the host response. We investigated the feasibility of rapid target discovery for novel broad-spectrum molecular therapeutics through comprehensive systems biology modeling and analysis of pathogen and host-response pathways and mechanisms. We developed a system to identify and prioritize candidate host targets based on strength of mechanistic evidence characterizing the role of the target in pathogenesis and tractability desiderata that include optimal delivery of new indications through potential repurposing of existing compounds or therapeutics. Empirical validation of predicted targets in cellular and mouse model systems documented an effective target prediction rate of 34%, suggesting that such computational discovery approaches should be part of target discovery efforts in operational clinical or biodefense research initiatives. We describe our target discovery methodology, technical implementation, and experimental results. Our work demonstrates the potential for in silico pathway models to enable rapid, systematic identification and prioritization of novel targets against existing or emerging biological threats, thus accelerating drug discovery and medical countermeasures research. BackgroundNew and reemerging infectious diseases pose a growing global health risk across public health concerns and potential bioterrorism threats. Pandemic viruses, resistant bacteria, and technology improvements in bioengineering point to a need for accelerated drug discovery 1 . One approach to this challenge is to use computational techniques to efficiently identify drug targets that may effectively mount a defense against one or more biothreats 2 . Biologically diverse pathogens share common or similar mechanism of infection and pathogenesis, and the host has similarly conserved immune response biology [3][4][5] .We have previously demonstrated the broad applicability of systems biology analyses to drug discovery and development focused on mammalian disease biology [8][9][10] . We hypothesize that similar computational characterization of pathogen biology, pathogenesis and hostresponse genomic pathways across multiple infectious agents can enable systematic identification of targets of intervention that will impact multiple pathogens in a similar manner, and thus serve as broad-spectrum drug targets that can be modulated by novel or

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Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

Cited by 11 publications

References 76 publications

Vaccine and adjuvant design for emerging viruses

Vaccine and adjuvant design for emerging viruses

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

Predictive Systems Biology Approach to Broad-Spectrum, Host-Directed Drug Target Discovery in Infectious Diseases

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