Adenoviral vector-based strategies against infectious disease and cancer

Zhang, Chao; Zhou, Dongming

doi:10.1080/21645515.2016.1165908

Cited by 95 publications

(86 citation statements)

References 140 publications

(131 reference statements)

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“…Infection by human AdV generally causes mild respiratory disease, although life-threatening disease can occur in immunocompromised individuals. The ability of AdV infection to efficiently stimulate cellular and humoral immune responses, coupled with the relative ease of genetic manipulation and large genome size, has led to their intensive investigation as gene delivery vectors [69].…”

Section: Adenoviridaementioning

confidence: 99%

Structure and Function of Viral Deubiquitinating Enzymes

Bailey-Elkin

Knaap

Kikkert

et al. 2017

Journal of Molecular Biology

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Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate and adaptive immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular deubiquitinating enzymes (DUBs), which remove ubiquitin from cellular targets and depolymerize polyubiquitin chains. The importance of protein ubiquitination to host immunity has been underscored by the discovery of viruses that encode proteases with deubiquitinating activity, many of which have been demonstrated to actively corrupt cellular ubiquitin-dependent processes to suppress innate antiviral responses and promote viral replication. DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. Here, we provide an overview of the structural biology of these fascinating viral enzymes and their role innate immune evasion and viral replication.

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Section: Adenoviridaementioning

confidence: 99%

Structure and Function of Viral Deubiquitinating Enzymes

Bailey-Elkin

Knaap

Kikkert

et al. 2017

Journal of Molecular Biology

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“…Adenoviruses have been used as viral vectors for decades (reviewed in [16]). Human adenoviruses have been developed as CHIKV viral-vectored vaccines, and they have been shown to induce robust immune responses in mice [17,18].…”

Section: Discussionmentioning

confidence: 99%

A Single and Un-Adjuvanted Dose of a Chimpanzee Adenovirus-Vectored Vaccine against Chikungunya Virus Fully Protects Mice from Lethal Disease

et al. 2019

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The mosquito-borne chikungunya virus (CHIKV) has become a major global health problem. Upon infection, chikungunya fever (CHIKF) can result in long-term joint pain and arthritis, and despite intense research, no licensed vaccine for CHIKV is available. We have developed two recombinant chimpanzee adenovirus-vectored vaccines (ChAdOx1) that induce swift and robust anti-CHIKV immune responses with a single dose, without the need for adjuvants or booster vaccines. Here, we report the vaccines' protective efficacies against CHIKV infection in a lethal A129 mouse model. Our results indicate that a single, un-adjuvanted ChAdOx1 Chik or ChAdOx1 Chik ∆Cap dose provided complete protection against a lethal virus challenge and prevented CHIKV-associated severe inflammation. These candidate vaccines supported survival equal to the attenuated 181/25 CHIKV reference vaccine but without the vaccine-related side effects, such as weight loss. Vaccination with either ChAdOx1 Chik or ChAdOx1 Chik ∆Cap resulted in high titers of neutralizing antibodies that are associated with protection, indicating that the presence of the capsid within the vaccine construct may not be essential to afford protection under the conditions tested. We conclude that both replication-deficient ChAdOx1 Chik vaccines are safe even when used in A129 mice and afford complete protection from a lethal challenge.

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“…EBAC has been applied with some success to the initial purification of adenoviral vectors [25] and hepatitis B core antigen (HBcAg) protein [26] from crude virus suspensions with Q and DEAE AG ligands, respectively. Adenovirus (AdV)-based vectors are widely used as vaccine vectors against infectious (bacterial and viral) diseases and cancer [84]. EBAC of unclarified culture bulk supplemented with Benzonase yielded 45% recovery and 5-fold concentration of adenoviral vectors whose purity compared to that obtained with the classical density gradient ultracentrifugation method [25].…”

Section: Ion-exchange Chromatography (Iec)mentioning

confidence: 98%