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Viruses Dec 2021Gene therapy is currently in the public spotlight. Several gene therapy products, including oncolytic virus (OV), which predominantly replicates in and kills cancer... (Review)
Review
Gene therapy is currently in the public spotlight. Several gene therapy products, including oncolytic virus (OV), which predominantly replicates in and kills cancer cells, and COVID-19 vaccines have recently been commercialized. Recombinant adenoviruses, including replication-defective adenoviral vector and conditionally replicating adenovirus (CRA; oncolytic adenovirus), have been extensively studied and used in clinical trials for cancer and vaccines. Here, we review the biology of wild-type adenoviruses, the methodological principle for constructing recombinant adenoviruses, therapeutic applications of recombinant adenoviruses, and new technologies in pluripotent stem cell (PSC)-based regenerative medicine. Moreover, this article describes the technology platform for efficient construction of diverse "CRAs that can specifically target tumors with multiple factors" (m-CRAs). This technology allows for modification of four parts in the adenoviral E1 region and the subsequent insertion of a therapeutic gene and promoter to enhance cancer-specific viral replication (i.e., safety) as well as therapeutic effects. The screening study using the m-CRA technology successfully identified survivin-responsive m-CRA (Surv.m-CRA) as among the best m-CRAs, and clinical trials of Surv.m-CRA are underway for patients with cancer. This article also describes new recombinant adenovirus-based technologies for solving issues in PSC-based regenerative medicine.
Topics: Adenoviridae; Adenoviridae Infections; Animals; COVID-19; COVID-19 Vaccines; Cell Line, Tumor; Gene Expression; Genetic Therapy; Genetic Vectors; Humans; Immunotherapy; Oncolytic Viruses; Pluripotent Stem Cells; Promoter Regions, Genetic; SARS-CoV-2; Survivin; Virus Replication
PubMed: 34960772
DOI: 10.3390/v13122502 -
Drug Metabolism and Pharmacokinetics Feb 2022Replication-incompetent adenovirus (Ad) vectors have been widely used as gene delivery vehicles in both gene therapy studies and basic studies for gene function analysis... (Review)
Review
Replication-incompetent adenovirus (Ad) vectors have been widely used as gene delivery vehicles in both gene therapy studies and basic studies for gene function analysis due to their highly advantageous properties, which include high transduction efficiencies, relatively large capacities for transgenes, and high titer production. In addition, Ad vectors induce moderate levels of innate immunity and have relatively high thermostability, making them very attractive as potential vaccine vectors. Accordingly, it is anticipated that Ad vectors will be used in vaccines for the prevention of infectious diseases, including Ebola virus disease and acquired immune deficiency syndrome (AIDS). Much attention is currently focused on the potential use of an Ad vector vaccine for coronavirus disease 2019 (COVID-19). In this review, we describe the basic properties of an Ad vector, Ad vector-induced innate immunity and immune responses to Ad vector-produced transgene products. Development of novel Ad vectors which can overcome the drawbacks of conventional Ad vector vaccines and clinical application of Ad vector vaccines to several infectious diseases are also discussed.
Topics: Adenoviridae; Adenovirus Vaccines; COVID-19; Communicable Diseases; Genetic Vectors; Humans; SARS-CoV-2; Vaccines
PubMed: 34974335
DOI: 10.1016/j.dmpk.2021.100432 -
Emerging Microbes & Infections Dec 2023African swine fever (ASF) is an acute and highly contagious lethal infectious disease in swine that severely threatens the global pig industry. At present, a safe and...
African swine fever (ASF) is an acute and highly contagious lethal infectious disease in swine that severely threatens the global pig industry. At present, a safe and efficacious vaccine is urgently required to prevent and control the disease. In this study, we evaluated the safety and immunogenicity of replication-incompetent type-2 adenoviruses carrying African swine fever virus (ASFV) antigens, namely (p30), (p54), (CD2v), (p72), and (p72 chaperone). A vaccine cocktail delivered by simultaneous intramuscular (IM) and intranasal (IN) administration robustly elicited both systemic and mucosal immune responses against AFSV in mice and swine and provided highly effective protection against the circulating ASFV strain in farmed pigs. This multi-antigen cocktail vaccine was well tolerated in the vaccinated animals. No significant interference among antigens was observed. The combined IM and IN vaccination using this adenovirus-vectored antigen cocktail vaccine warrants further evaluation for providing safe and effective protection against ASFV infection and transmission.
Topics: Swine; Animals; Mice; African Swine Fever Virus; African Swine Fever; Adenoviridae; Adenovirus Vaccines; Antigens, Viral; Viral Vaccines; Adenoviridae Infections; Vaccination
PubMed: 37401832
DOI: 10.1080/22221751.2023.2233643 -
Annual Review of Medicine Jan 2022The worldwide pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the unprecedented pace of... (Review)
Review
The worldwide pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the unprecedented pace of development of multiple vaccines. This review evaluates how adenovirus (Ad) vector platforms have been leveraged in response to this pandemic. Ad vectors have been used in the past for vaccines against other viruses, most notably HIV and Ebola, but they never have been produced, distributed, or administered to humans at such a large scale. Several different serotypes of Ads encoding SARS-CoV-2 Spike have been tested and found to be efficacious against COVID-19. As vaccine rollouts continue and the number of people receiving these vaccines increases, we will continue to learn about this vaccine platform for COVID-19 prevention and control.
Topics: COVID-19; COVID-19 Vaccines; Genetic Vectors; Humans; Pandemics; SARS-CoV-2
PubMed: 34609905
DOI: 10.1146/annurev-med-012621-102252 -
Anaesthesia, Critical Care & Pain... Dec 2020
Topics: Adenoviridae; Antibodies, Neutralizing; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Drug Development; Humans; RNA, Messenger; SARS-CoV-2; Vaccines, Inactivated
PubMed: 33096260
DOI: 10.1016/j.accpm.2020.10.006 -
Vaccines Nov 2023Respiratory syncytial virus (RSV) infection and shingles are two viral diseases that affect older adults, and a combined vaccine to protect against both could be...
Respiratory syncytial virus (RSV) infection and shingles are two viral diseases that affect older adults, and a combined vaccine to protect against both could be beneficial. RSV infection causes hospitalisations and significant morbidity in both children and adults and can be fatal in the elderly. The RSV fusion (F) envelope glycoprotein induces a strong RSV-neutralising antibody response and is the target of protective immunity in the first RSV vaccine for older adults, recently approved by the FDA. An initial childhood infection with the varicella zoster virus (VZV) results in chickenpox disease, but reactivation in older adults can cause shingles. This reactivation in sensory and autonomic neurons is characterized by a skin-blistering rash that can be accompanied by prolonged pain. The approved protein-in-adjuvant shingles vaccine induces VZV glycoprotein E (gE)-fspecific antibody and CD4 T cell responses and is highly effective. Here we report the evaluation of RSV/shingles combination vaccine candidates based on non-replicating chimpanzee adenovirus (ChAd) vectors. We confirmed the cellular and humoral immunogenicity of the vaccine vectors in mice using T cell and antibody assays. We also carried out an RSV challenge study in cotton rats which demonstrated protective efficacy following a homologous prime-boost regimen with our preferred vaccine candidate.
PubMed: 38006010
DOI: 10.3390/vaccines11111679 -
Molecular Therapy. Nucleic Acids Dec 2023Adenoviral vectors have been widely used as vaccine candidates or potential vaccine candidates against infectious diseases due to the convenience of genome manipulation,... (Review)
Review
Adenoviral vectors have been widely used as vaccine candidates or potential vaccine candidates against infectious diseases due to the convenience of genome manipulation, their ability to accommodate large exogenous gene fragments, easy access of obtaining high-titer of virus, and high efficiency of transduction. At the same time, adenoviral vectors have also been used extensively in clinical research for cancer gene therapy and treatment of diseases caused by a single gene defect. However, application of adenovirus also faces a series of challenges such as poor targeting, strong immune response against the vector itself, and they cannot be used repeatedly. It is believed that these problems will be solved gradually with further research and technological development in related fields. Here, we review the construction methods of adenoviral vectors, including "gutless" adenovirus and discuss application of adenoviral vectors as prophylactic vaccines for infectious pathogens and their application prospects as therapeutic vaccines for cancer and other kinds of chronic infectious disease such as human papillomavirus, hepatitis B virus, and hepatitis C virus.
PubMed: 37808925
DOI: 10.1016/j.omtn.2023.09.004 -
Bioengineered Bugs 2010is a zoonotic, intracellular bacterium, found in a wide range of birds, and is the causative agent of psittacosis, or avian chlamydiosis (AC). AC, as well as having...
is a zoonotic, intracellular bacterium, found in a wide range of birds, and is the causative agent of psittacosis, or avian chlamydiosis (AC). AC, as well as having significant zoonotic potential, causes high mortality in domestic birds, and there is no effective commercial vaccine. The group of Zhou et al. has generated recombinant adenovirus vaccines, which exhibit significant potential for the prophylactic treatment of poultry. Reduction of AC will affect not only the disease and associated mortality, but should also reduce the incidence of the carrier state, and should improve breeding performance in birds. Design and successful vaccine implementation also has the potential to improve human health, by decreasing zoonotic risk and should also reduce the risk of emergence of antibiotic resistant strains.
Topics: Animals; Aviadenovirus; Bacterial Outer Membrane Proteins; Bacterial Vaccines; Chickens; Chlamydia; Chlamydia Infections; HEK293 Cells; Humans; Immunization
PubMed: 21327061
DOI: 10.4161/bbug.1.4.12117 -
Canadian Family Physician Medecin de... Jun 2022
Topics: Adenoviridae; Adenovirus Vaccines; COVID-19; COVID-19 Vaccines; Humans; Thrombocytopenia; Vaccines
PubMed: 35701204
DOI: 10.46747/cfp.6806434