-
Viruses Mar 2023Viral vectors have been used for a broad spectrum of gene therapy for both acute and chronic diseases. In the context of cancer gene therapy, viral vectors expressing... (Review)
Review
Viral vectors have been used for a broad spectrum of gene therapy for both acute and chronic diseases. In the context of cancer gene therapy, viral vectors expressing anti-tumor, toxic, suicide and immunostimulatory genes, such as cytokines and chemokines, have been applied. Oncolytic viruses, which specifically replicate in and kill tumor cells, have provided tumor eradication, and even cure of cancers in animal models. In a broader meaning, vaccine development against infectious diseases and various cancers has been considered as a type of gene therapy. Especially in the case of COVID-19 vaccines, adenovirus-based vaccines such as ChAdOx1 nCoV-19 and Ad26.COV2.S have demonstrated excellent safety and vaccine efficacy in clinical trials, leading to Emergency Use Authorization in many countries. Viral vectors have shown great promise in the treatment of chronic diseases such as severe combined immunodeficiency (SCID), muscular dystrophy, hemophilia, β-thalassemia, and sickle cell disease (SCD). Proof-of-concept has been established in preclinical studies in various animal models. Clinical gene therapy trials have confirmed good safety, tolerability, and therapeutic efficacy. Viral-based drugs have been approved for cancer, hematological, metabolic, neurological, and ophthalmological diseases as well as for vaccines. For example, the adenovirus-based drug Gendicine for non-small-cell lung cancer, the reovirus-based drug Reolysin for ovarian cancer, the oncolytic HSV T-VEC for melanoma, lentivirus-based treatment of ADA-SCID disease, and the rhabdovirus-based vaccine Ervebo against Ebola virus disease have been approved for human use.
Topics: Animals; Humans; Ad26COVS1; Carcinoma, Non-Small-Cell Lung; ChAdOx1 nCoV-19; Genetic Therapy; Genetic Vectors; Lung Neoplasms
PubMed: 36992407
DOI: 10.3390/v15030698 -
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 -
Medicine (Abingdon, England : UK Ed.) Nov 2017This article reviews the virology, immunology and epidemiology of the most common viral causes of acute gastroenteritis (rotaviruses, human caliciviruses, astroviruses,... (Review)
Review
This article reviews the virology, immunology and epidemiology of the most common viral causes of acute gastroenteritis (rotaviruses, human caliciviruses, astroviruses, enteric adenoviruses). Clinical symptoms range from mild diarrhoea to life-threatening dehydration, and rotavirus disease is a major cause of childhood mortality, mainly in developing countries. The diagnosis, treatment and preventive measures are reviewed. Uncommon viral causes of acute gastroenteritis and viruses causing gastroenteritis in immunodeficient patients are also discussed. Two live attenuated rotavirus vaccines (Rotarix, RotaTeq) have been licensed in >100 countries since 2006 and used in universal mass vaccination (UMV) programmes. In addition, a new rotavirus vaccine was licensed in India in 2015 for UMV. Although rotavirus vaccines are highly effective in industrialized countries, they are less so in low-income countries of sub-Saharan Africa and South-East Asia. Vaccines against human norovirus disease are under development. Major progress has recently been made in basic research on rotaviruses and human caliciviruses.
PubMed: 32288581
DOI: 10.1016/j.mpmed.2017.08.005 -
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 -
Molecular Therapy : the Journal of the... Nov 2020
Topics: Adenovirus Vaccines; Animals; Betacoronavirus; COVID-19; COVID-19 Vaccines; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Viral Vaccines
PubMed: 33065038
DOI: 10.1016/j.ymthe.2020.10.002 -
Viruses Feb 2021Vaccine development against SARS-CoV-2 has been fierce due to the devastating COVID-19 pandemic and has included all potential approaches for providing the global... (Review)
Review
Vaccine development against SARS-CoV-2 has been fierce due to the devastating COVID-19 pandemic and has included all potential approaches for providing the global community with safe and efficient vaccine candidates in the shortest possible timeframe. Viral vectors have played a central role especially using adenovirus-based vectors. Additionally, other viral vectors based on vaccinia viruses, measles viruses, rhabdoviruses, influenza viruses and lentiviruses have been subjected to vaccine development. Self-amplifying RNA virus vectors have been utilized for lipid nanoparticle-based delivery of RNA as COVID-19 vaccines. Several adenovirus-based vaccine candidates have elicited strong immune responses in immunized animals and protection against challenges in mice and primates has been achieved. Moreover, adenovirus-based vaccine candidates have been subjected to phase I to III clinical trials. Recently, the simian adenovirus-based ChAdOx1 vector expressing the SARS-CoV-2 S spike protein was approved for use in humans in the UK.
Topics: Adenoviridae; Animals; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Genetic Vectors; Humans; Mice; Pandemics; RNA, Viral; Viral Vaccines
PubMed: 33669550
DOI: 10.3390/v13020317