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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 -
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 -
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 -
Vaccines Oct 2023Inducing humoral and cytotoxic mucosal immunity at the sites of pathogen entry has the potential to prevent the infection from getting established. This is different... (Review)
Review
Inducing humoral and cytotoxic mucosal immunity at the sites of pathogen entry has the potential to prevent the infection from getting established. This is different from systemic vaccination, which protects against the development of systemic symptoms. The field of mucosal vaccination has seen fewer technological advances compared to nucleic acid and subunit vaccine advances for injectable vaccine platforms. The advent of the next-generation adenoviral vectors has given a boost to mucosal vaccine research. Basic research into the mechanisms regulating innate and adaptive mucosal immunity and the discovery of effective and safe mucosal vaccine adjuvants will continue to improve mucosal vaccine design. The results from clinical trials of inhaled COVID-19 vaccines demonstrate their ability to induce the proliferation of cytotoxic T cells and the production of secreted IgA and IgG antibodies locally, unlike intramuscular vaccinations. However, these mucosal vaccines induce systemic immune responses at par with systemic vaccinations. This review summarizes the function of the respiratory mucosa-associated lymphoid tissue and the advantages that the adenoviral vectors provide as inhaled vaccine platforms.
PubMed: 37896988
DOI: 10.3390/vaccines11101585 -
Frontiers in Genome Editing 2020The current COVID-19 pandemic has substantially accelerated the demands for efficient vaccines. A wide spectrum of approaches includes live attenuated and inactivated... (Review)
Review
The current COVID-19 pandemic has substantially accelerated the demands for efficient vaccines. A wide spectrum of approaches includes live attenuated and inactivated viruses, protein subunits and peptides, viral vector-based delivery, DNA plasmids, and synthetic mRNA. Preclinical studies have demonstrated robust immune responses, reduced viral loads and protection against challenges with SARS-CoV-2 in rodents and primates. Vaccine candidates based on all delivery systems mentioned above have been subjected to clinical trials in healthy volunteers. Phase I clinical trials have demonstrated in preliminary findings good safety and tolerability. Evaluation of immune responses in a small number of individuals has demonstrated similar or superior levels of neutralizing antibodies in comparison to immunogenicity detected in COVID-19 patients. Both adenovirus- and mRNA-based vaccines have entered phase II and study protocols for phase III trials with 30,000 participants have been finalized.
PubMed: 34713220
DOI: 10.3389/fgeed.2020.579297 -
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 -
European Journal of Internal Medicine Nov 2022Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome characterized by high-titer anti-platelet factor 4 (PF4) antibodies, thrombocytopenia... (Review)
Review
Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome characterized by high-titer anti-platelet factor 4 (PF4) antibodies, thrombocytopenia and arterial and venous thrombosis in unusual sites, as cerebral venous sinuses and splanchnic veins. VITT has been described to occur almost exclusively after administration of ChAdOx1 nCoV-19 and Ad26.COV2.S adenovirus vector- based COVID-19 vaccines. Clinical and laboratory features of VITT resemble those of heparin-induced thrombocytopenia (HIT). It has been hypothesized that negatively charged polyadenylated hexone proteins of the AdV vectors could act as heparin to induce the conformational changes of PF4 molecule that lead to the formation of anti-PF4/polyanion antibodies. The anti-PF4 immune response in VITT is fostered by the presence of a proinflammatory milieu, elicited by some impurities found in ChAdOx1 nCoV-19 vaccine, as well as by soluble spike protein resulting from alternative splice events. Anti-PF4 antibodies bind PF4, forming immune complexes which activate platelets, monocytes and granulocytes, resulting in the VITT's immunothrombosis. The reason why only a tiny minority of patents receiving AdV-based COVID-19 vaccines develop VITT is still unknown. It has been hypothesized that individual intrinsic factors, either acquired (i.e., pre-priming of B cells to produce anti-PF4 antibodies by previous contacts with bacteria or viruses) or inherited (i.e., differences in platelet T-cell ubiquitin ligand-2 [TULA-2] expression) can predispose a few subjects to develop VITT. A better knowledge of the mechanistic basis of VITT is essential to improve the safety and the effectiveness of future vaccines and gene therapies using adenovirus vectors.
Topics: Humans; Antigen-Antibody Complex; COVID-19 Vaccines; Ad26COVS1; ChAdOx1 nCoV-19; Ligands; Spike Glycoprotein, Coronavirus; COVID-19; Platelet Factor 4; Heparin; Thrombocytopenia; Thrombosis; Vaccines; Purpura, Thrombocytopenic, Idiopathic; Ubiquitins
PubMed: 35953336
DOI: 10.1016/j.ejim.2022.08.002 -
Microbial Biotechnology Jul 2021Under the pressure of the COVID-19 pandemic, vaccines were developed and rolled out into mass vaccination campaigns at incredible speed. What normally takes a decade was...
Under the pressure of the COVID-19 pandemic, vaccines were developed and rolled out into mass vaccination campaigns at incredible speed. What normally takes a decade was worked out within a year. Vaccines were produced along many different platforms ranging from inactivated whole virus vaccines over adenovirus-vectored vaccines, recombinant protein vaccines and nanoparticles to mRNA vaccines. Several vaccines went through preclinical testing and completed successful phase 1 to phase 3 clinical trials. The first evaluations of national vaccination campaigns document astonishing high levels of protection against disease. The present article summarizes the published reports leading to these striking achievements with vaccines based on different concepts.
Topics: COVID-19; COVID-19 Vaccines; Genetic Vectors; Humans; Pandemics; Vaccines, Synthetic
PubMed: 33960659
DOI: 10.1111/1751-7915.13818 -
Journal of Pharmaceutical Sciences Apr 2023Adenovirus vectors have become an important class of vaccines with the recent approval of Ebola and COVID-19 products. In-process quality attribute data collected during...
Adenovirus vectors have become an important class of vaccines with the recent approval of Ebola and COVID-19 products. In-process quality attribute data collected during Adenovirus vector manufacturing has focused on particle concentration and infectivity ratios (based on viral genome: cell-based infectivity), and data suggest only a fraction of viral particles present in the final vaccine product are efficacious. To better understand this product heterogeneity, lab-scale preparations of two Adenovirus viral vectors, (Chimpanzee adenovirus (ChAdOx1) and Human adenovirus Type 5 (Ad5), were studied using transmission electron microscopy (TEM). Different adenovirus morphologies were characterized, and the proportion of empty and full viral particles were quantified. These proportions showed a qualitative correlation with the sample's infectivity values. Liquid chromatography-mass spectrometry (LC-MS) peptide mapping was used to identify key adenovirus proteins involved in viral maturation. Using peptide abundance analysis, a ∼5-fold change in L1 52/55k abundance was observed between low-(empty) and high-density (full) fractions taken from CsCl ultracentrifugation preparations of ChAdOx1 virus. The L1 52/55k viral protein is associated with DNA packaging and is cleaved during viral maturation, so it may be a marker for infective particles. TEM and LC-MS peptide mapping are promising higher-resolution analytical characterization tools to help differentiate between relative proportions of empty, non-infectious, and infectious viral particles as part of Adenovirus vector in-process monitoring, and these results are an encouraging initial step to better differentiate between the different product-related impurities.
Topics: Humans; Capsid; COVID-19; Viral Proteins; Adenoviridae; Adenoviruses, Human; Genetic Vectors
PubMed: 36563855
DOI: 10.1016/j.xphs.2022.12.012