-
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 -
Immune Network Feb 2021Adenovirus was originally used as a vector for gene therapy. In recent years, with the development of the next-generation vectors with increased safety and high... (Review)
Review
Adenovirus was originally used as a vector for gene therapy. In recent years, with the development of the next-generation vectors with increased safety and high immunogenicity to transgene products, its utility as a vaccine vector has continued to increase. Adenovirus-based vaccines are currently being tested not only to prevent various infectious diseases but also to be applied as cancer vaccines. In this review, I discuss the innate and adaptive aspects of the immunological characteristics of adenovirus vectors and further examine the current status of advanced adenovirus-based vaccine development. Various methods that can overcome the limitations of currently used adenoviruses as vaccine vehicles are also discussed. Through this study, I hope that vaccine development using adenovirus vectors will be expedited and more successful.
PubMed: 33728099
DOI: 10.4110/in.2021.21.e6 -
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 -
Reviews in Medical Virology Nov 2022Due to their nature, adenoviruses have been recognised as promising candidates for vaccine vector development. Since they mimic natural infection, recombinant adenovirus... (Review)
Review
Due to their nature, adenoviruses have been recognised as promising candidates for vaccine vector development. Since they mimic natural infection, recombinant adenovirus vectors have been proven as ideal shuttles to deliver foreign transgenes aiming at inducing both humoral and cellular immune response. In addition, a potent adjuvant effect can be exerted due to the adenovirus inherent stimulation of various elements of innate and adaptive immunity. Due to its low seroprevalence in humans as well as induction of favourable immune response to inserted transgene, human adenovirus type 26 (HAdV-D26) has been recognised as a promising platform for vaccine vector development and is studied in number of completed or ongoing clinical studies. Very recently HAdV-D26 based Ebola and Covid-19 vaccines were approved for medical use. In this review, current state of the art regarding HAdV-D26 basic biology and its usage as vaccine vector will be discussed.
Topics: Humans; Adenoviruses, Human; Seroepidemiologic Studies; COVID-19 Vaccines; COVID-19; Adenoviridae; Genetic Vectors; Vaccines; Biology
PubMed: 35278248
DOI: 10.1002/rmv.2338 -
Expert Review of Vaccines Feb 2018Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk... (Review)
Review
INTRODUCTION
Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines.
AREAS COVERED
This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared.
EXPERT COMMENTARY
The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.
Topics: Adenoviridae; Animals; Cancer Vaccines; Genetic Vectors; Humans; Proteins; Vaccines, Attenuated
PubMed: 29251011
DOI: 10.1080/14760584.2018.1419067 -
Vaccine Jan 2015The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry... (Review)
Review
The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle.
Topics: Animals; Cattle; Drug Carriers; Drug Discovery; Genetic Vectors; Immunity, Cellular; Immunity, Humoral; Mastadenovirus; Vaccines, Attenuated; Vaccines, Synthetic; Veterinary Medicine
PubMed: 25498212
DOI: 10.1016/j.vaccine.2014.11.055 -
Viruses Jun 2021Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses... (Review)
Review
Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses combine many desirable features of a genetic vaccine. They are highly immunogenic and have a low and well characterized pathogenic profile paired with technological approachability. Ongoing efforts to improve adenovirus-vaccine vectors include the use of rare serotypes and non-human adenoviruses. In this review, we focus on the viral capsid and how the choice of genotypes influences the uptake and subsequent subcellular sorting. We describe how understanding capsid properties, such as stability during the entry process, can change the fate of the entering particles and how this translates into differences in immunity outcomes. We discuss in detail how mutating the membrane lytic capsid protein VI affects species C viruses' post-entry sorting and briefly discuss if such approaches could have a wider implication in vaccine and/or vector development.
Topics: Adaptive Immunity; Adenoviruses, Human; Animals; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; Capsid; Capsid Proteins; Clinical Trials as Topic; Genetic Vectors; Humans; Immunity, Innate; Mice; SARS-CoV-2; Viral Vaccines; Virus Internalization
PubMed: 34202573
DOI: 10.3390/v13071221 -
Expert Opinion on Biological Therapy Jun 2010Tumor associated antigens (TAAs) offer specific targets for developing cancer immunotherapies. In particular, viral vectors encoding transgenic TAAs have been used in... (Review)
Review
IMPORTANCE OF THE FIELD
Tumor associated antigens (TAAs) offer specific targets for developing cancer immunotherapies. In particular, viral vectors encoding transgenic TAAs have been used in recent vaccination strategies. Wilm's Tumor gene (WT1) is a robust TAA which is overexpressed in many malignancies and has been recently used to develop a novel recombinant adenovirus (Ad-WT1) for antitumor immunotherapy.
AREAS COVERED IN THIS REVIEW
The lines of evidence over the past two decades leading to the development of Ad-WT1 immunotherapy are reviewed, including preclinical studies and clinical trials using WT1-based vaccines and TAA-expressing adenoviral vectors for antitumor therapy.
WHAT THE READER WILL GAIN
The fundamental immunogenic properties of WT1-based vaccines are detailed, as well as the recent progress in using adenoviral vectors for eliciting a TAA-specific immune response. The reader will also gain an understanding of the evidence supporting Ad-WT1 antitumor therapy in vivo.
TAKE HOME MESSAGE
Ad-WT1 elicits a potent CD4(+) and CD8(+) T cell immune response and can effectively inhibit tumor growth in vivo, thus making it an important potential cancer therapy worthy of future investigation.
Topics: Adenoviridae; Animals; Clinical Trials as Topic; Genes, Wilms Tumor; Humans; Neoplasms; Viral Vaccines
PubMed: 20380487
DOI: 10.1517/14712591003798278 -
Emerging Infectious Diseases Jun 2023The US Coast Guard Academy began adenovirus vaccination of incoming cadets in 2022. Of 294 vaccine recipients, 15%-20% had mild respiratory or systemic symptoms within...
The US Coast Guard Academy began adenovirus vaccination of incoming cadets in 2022. Of 294 vaccine recipients, 15%-20% had mild respiratory or systemic symptoms within 10 days postvaccination but no serious adverse events after 90 days. Our findings support the continued use of adenovirus vaccines in congregate military settings.
Topics: United States; Humans; Adenovirus Vaccines; Military Personnel
PubMed: 37209695
DOI: 10.3201/eid2906.230331 -
Expert Review of Vaccines Nov 2011The disease-fighting power of vaccines has been a public health bonanza credited with the worldwide reduction of mortality and morbidity. The goal to further amplify its... (Review)
Review
The disease-fighting power of vaccines has been a public health bonanza credited with the worldwide reduction of mortality and morbidity. The goal to further amplify its power by boosting vaccine coverage requires the development of a new generation of rapid-response vaccines that can be mass produced at low costs and mass administered by nonmedical personnel. The new vaccines also have to be endowed with a higher safety margin than that of conventional vaccines. The nonreplicating adenovirus-vectored vaccine holds promise in boosting vaccine coverage because the vector can be rapidly manufactured in serum-free suspension cells in response to a surge in demand, and noninvasively administered by nasal spray into human subjects in compliance with evolutionary medicine. In contrast to parenteral injection, noninvasive mucosal vaccination minimizes systemic inflammation. Moreover, pre-existing adenovirus immunity does not interfere appreciably with the potency of an adenovirus-vectored nasal vaccine. Nasal administration of adenovirus vectors encoding pathogen antigens is not only fear-free and painless, but also confers rapid and sustained protection against mucosal pathogens as a drug-vaccine duo since adenovirus particles alone without transgene expression can induce an anti-influenza state in the airway. In addition to human vaccination, animals can also be mass immunized by this class of vectored vaccines.
Topics: Adenoviruses, Human; Administration, Intranasal; Drug Carriers; Drug Delivery Systems; Genetic Vectors; Humans; Vaccination; Vaccines
PubMed: 22043954
DOI: 10.1586/erv.11.141