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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 -
Trends in Molecular Medicine Jan 2023The consequences of human adenovirus (HAdV) infections are generally mild. However, despite the perception that HAdVs are harmless, infections can cause severe disease... (Review)
Review
The consequences of human adenovirus (HAdV) infections are generally mild. However, despite the perception that HAdVs are harmless, infections can cause severe disease in certain individuals, including newborns, the immunocompromised, and those with pre-existing conditions, including respiratory or cardiac disease. In addition, HAdV outbreaks remain relatively common events and the recent emergence of more pathogenic genomic variants of various genotypes has been well documented. Coupled with evidence of zoonotic transmission, interspecies recombination, and the lack of approved AdV antivirals or widely available vaccines, HAdVs remain a threat to public health. At the same time, the detailed understanding of AdV biology garnered over nearly 7 decades of study has made this group of viruses a molecular workhorse for vaccine and gene therapy applications.
Topics: Infant, Newborn; Humans; Adenoviridae; Adenovirus Infections, Human; Adenoviruses, Human; Genomics; Genotype; Phylogeny; Respiratory Tract Infections
PubMed: 36336610
DOI: 10.1016/j.molmed.2022.10.001 -
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 -
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 -
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 -
International Journal of Public Health 2023This umbrella meta-analysis aims to provide comprehensive and synthesized evidence regarding the effectiveness and safety of COVID-19 vaccinations based on current... (Meta-Analysis)
Meta-Analysis Review
This umbrella meta-analysis aims to provide comprehensive and synthesized evidence regarding the effectiveness and safety of COVID-19 vaccinations based on current studies. Studies from the Cochrane Library, PubMed, and EMBASE, published before 10 December 2021, were included in the analysis. The pooled results of effectiveness and safety were estimated and shown in forest plots. We included nineteen studies (fifteen studies regarding safety and nine regarding effectiveness) in the analysis. The mRNA vaccines, adenovirus vector vaccines, subunit vaccines, and inactivated vaccines were found to be effective; however, mRNA vaccines, adenovirus vector vaccines and subunit vaccines were associated with local adverse events and systemic events when compared with inactivated vaccines. Our study suggested that till date, COVID-19 vaccination is still a preferred pharmaceutical way to control the widespread pandemic. However, all reported adverse events should be revisited to provide further evidence for mass vaccinations.
Topics: Humans; COVID-19 Vaccines; Adenovirus Vaccines; COVID-19; Vaccination; RNA, Messenger
PubMed: 37485047
DOI: 10.3389/ijph.2023.1605526 -
Clinical Medicine (London, England) Mar 2022In the new science emanating from the COVID-19 pandemic, effective vaccine development has made a huge difference and saved countless lives. Vaccine roll-out led to the... (Review)
Review
In the new science emanating from the COVID-19 pandemic, effective vaccine development has made a huge difference and saved countless lives. Vaccine roll-out led to the identification of rare cases of severe thrombotic and thrombocytopenic problems in some recipients. This apparent coupling of thrombosis with haemorrhagic potentiation might seem baffling but the ensuing clinical investigation rapidly shed important light on its molecular mechanism. This review outlines the current understanding on the role of adenovirus-based platforms, the immunogenic triggers and the immunothrombotic response underlying vaccine-induced immune thrombotic thrombocytopenia.
Topics: COVID-19; COVID-19 Vaccines; Humans; Pandemics; SARS-CoV-2; Thrombocytopenia; Thrombosis; Vaccines
PubMed: 35273026
DOI: 10.7861/clinmed.2022-0006 -
Cells Oct 2021As of September 2021, twenty-one anti-COVID-19 vaccines have been approved in the world. Their utilization will expedite an end to the current pandemic. Besides the... (Review)
Review
As of September 2021, twenty-one anti-COVID-19 vaccines have been approved in the world. Their utilization will expedite an end to the current pandemic. Besides the usual vaccine formats that include inactivated viruses (eight approved vaccines) and protein-based vaccines (four approved vaccines), three new formats have been validated: recombinant adenovirus (six approved vaccines), DNA (one approved vaccine), and messenger RNA (mRNA, two approved vaccines). The latter was the fastest (authorized in 2020 in the EU, the USA, and Switzerland). Most Western countries have reserved or use the protein vaccines, the adenovirus vaccines, and mRNA vaccines. I describe here the different vaccine formats in the context of COVID-19, detail the three formats that are chiefly reserved or used in Europe, Canada, and the USA, and discuss why the mRNA vaccines appear to be the superior format.
Topics: Adenoviridae; Animals; COVID-19; COVID-19 Vaccines; Canada; DNA; Drug Approval; Europe; Humans; Mice; Patient Safety; RNA, Messenger; SARS-CoV-2; Spike Glycoprotein, Coronavirus; United States
PubMed: 34685696
DOI: 10.3390/cells10102716 -
Viruses Apr 2022About two years have passed since the identification of SARS-CoV-2 in China. The rapid spread of this virus all over the world and its high transmissibility and... (Review)
Review
About two years have passed since the identification of SARS-CoV-2 in China. The rapid spread of this virus all over the world and its high transmissibility and pathogenicity in humans have resulted in a global pandemic. The negative impact of COVID-19 on health, society and the economy at the global level has pushed researchers and pharmaceutical companies to develop effective vaccines to fight SARS-CoV-2. Thanks to this collaborative effort, the first COVID-19 vaccine was developed in less than a year. Since then, several COVID-19 vaccines have been validated for use by the World Health Organization. Among these, mRNA- (BNT162b2 and mRNA1273) and adenovirus-based (ChAdOx1) vaccines were developed through the use of novel technologies. While all three of these vaccines have shown effectiveness against the COVID-19 disease and their immunogenicity was characterized in clinical trials in the general population, data on their efficacy and immunogenicity in people living with HIV (PLWH) are limited. In this review, we provide a description of the characteristics of mRNA- and adenovirus-based vaccines and of the immune response elicited in the general population by vaccination. Then we describe the use of these vaccines and their efficacy and immunogenicity in people living with HIV and we conclude with a discussion regarding some open questions concerning the use of mRNA- and adenovirus-based COVID-19 vaccines in PLWH.
Topics: Adenoviridae; Adenoviridae Infections; Adenovirus Vaccines; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; HIV Seropositivity; Humans; Immunogenicity, Vaccine; RNA, Messenger; SARS-CoV-2; Vaccination
PubMed: 35458478
DOI: 10.3390/v14040748 -
Infectious Disorders Drug Targets 2023Restoring everyday civil life from the devastating pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be only by the development of an...
Restoring everyday civil life from the devastating pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be only by the development of an efficient vaccine. As of April 12, 2022, 497,960,492 confirmed cases of COVID-19 were reported, including 6,181,850 lives having been lost worldwide and completely paralyzing the d global economy. Detection of a novel coronavirus SARS-CoV-2 in Wuhan, in December 2019, and the genetic sequence of SARS-CoV-2 that was published on January 11, 2020, leads to a global race, to prepare for a preventive vaccine. No single institution can develop a vaccine individually because there are many stages for developing and producing a successful vaccine. Since this virus threatens the health, the economy, and society the demand for a fast-track vaccine is understandable. This article tries to give an overview of vaccine 'candidates' development and clinical trials, and it mentions some challenges of using these vaccines for managing SARS-CoV-2.
Topics: Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Viral Vaccines; Pandemics
PubMed: 35984031
DOI: 10.2174/1871526522666220818124416