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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 -
Future Virology Sep 2016Replication incompetent human adenovirus serotype 5 (HAdV-C5) has been extensively used as a delivery vehicle for gene therapy proteins and infectious disease antigens.... (Review)
Review
Replication incompetent human adenovirus serotype 5 (HAdV-C5) has been extensively used as a delivery vehicle for gene therapy proteins and infectious disease antigens. These vectors infect replicating and nonreplicating cells, have a broad tissue tropism, elicit high immune responses and are easily purified to high titers. However, the utility of HAdV-C5 vectors as potential vaccines is limited due to pre-existing immunity within the human population that significantly reduces the immunogenicity of HAdV-C5 vaccines. In recent years, adenovirus vaccine development has focused on simian-derived adenoviral vectors, which have the desirable vector characteristics of HAdV-C5 but with negligible seroprevalence in the human population. Here, we discuss recent advances in simian adenovirus vaccine vector development and evaluate current research specifically focusing on clinical trial data.
PubMed: 29527232
DOI: 10.2217/fvl-2016-0070 -
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 -
Biotechnology Journal May 2015Efforts to make vaccines against infectious diseases and immunotherapies for cancer have evolved to utilize a variety of heterologous expression systems such as viral... (Review)
Review
Efforts to make vaccines against infectious diseases and immunotherapies for cancer have evolved to utilize a variety of heterologous expression systems such as viral vectors. These vectors are often attenuated or engineered to safely deliver genes encoding antigens of different pathogens. Adenovirus and poxvirus vectors are among the viral vectors that are most frequently used to develop prophylactic vaccines against infectious diseases as well as therapeutic cancer vaccines. This mini-review describes the trends and processes in large-scale production of adenovirus and poxvirus vectors to meet the needs of clinical applications. We briefly describe the general principles for the production and purification of adenovirus and poxvirus viral vectors. Currently, adenovirus and poxvirus vector manufacturing methods rely on well-established cell culture technologies. Several improvements have been evaluated to increase the yield and to reduce the overall manufacturing cost, such as cultivation at high cell densities and continuous downstream processing. Additionally, advancements in vector characterization will greatly facilitate the development of novel vectored vaccine candidates.
Topics: Adenoviridae; Batch Cell Culture Techniques; Cell Count; Clinical Trials as Topic; Genetic Vectors; Humans; Poxviridae; Viral Vaccines; Virus Cultivation
PubMed: 25914340
DOI: 10.1002/biot.201400390 -
The Cochrane Database of Systematic... May 2017The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore... (Review)
Review
BACKGROUND
The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8º C). The widespread morbidity caused by the common cold worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. This is an update of a Cochrane review first published in 2011 and previously updated in 2013.
OBJECTIVES
To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2016), MEDLINE (1948 to September 2016), Embase (1974 to September 2016), CINAHL (1981 to September 2016), and LILACS (1982 to September 2016). We also searched three trials registers for ongoing studies and four websites for additional trials (February 2017). We included no language or date restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of any virus vaccines compared with placebo to prevent the common cold in healthy people.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated methodological quality and extracted trial data. We resolved disagreements by discussion or by consulting a third review author.
MAIN RESULTS
We found no additional RCTs for inclusion in this update. This review includes one RCT dating from the 1960s with an overall high risk of bias. The RCT included 2307 healthy participants, all of whom were included in analyses. This trial compared the effect of an adenovirus vaccine against placebo. No statistically significant difference in common cold incidence was found: there were 13 (1.14%) events in 1139 participants in the vaccines group and 14 (1.19%) events in 1168 participants in the placebo group (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; P = 0.90). No adverse events related to the live vaccine were reported. The quality of the evidence was low due to limitations in methodological quality and a wide 95% confidence interval.
AUTHORS' CONCLUSIONS
This Cochrane Review was based on one study with low-quality evidence. We found no conclusive results to support the use of vaccines for preventing the common cold in healthy people compared with placebo. We identified a need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety, and mortality related to the vaccine.
Topics: Adenovirus Vaccines; Common Cold; Health Status; Humans; Randomized Controlled Trials as Topic; Vaccines, Attenuated
PubMed: 28516442
DOI: 10.1002/14651858.CD002190.pub5 -
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 -
Expert Review of Vaccines 2015In 2014, an outbreak of Ebola virus spread rapidly in West Africa. The epidemic killed more than 10,000 people and resulted in transmissions outside the endemic... (Review)
Review
In 2014, an outbreak of Ebola virus spread rapidly in West Africa. The epidemic killed more than 10,000 people and resulted in transmissions outside the endemic countries. WHO hopes for effective vaccines by the end of 2015. Numerous vaccine candidates have been proposed, and several are currently being evaluated in humans. Among the vaccine candidates are vectors derived from adenovirus (Ad). Despite previous encouraging preclinical and Phase I/II trials, Ad vectors used in three Phase II trials targeting HIV were prematurely interrupted because of the lack of demonstrated efficacy. The vaccine was not only ineffective but also led to a higher rate of HIV acquisition. In this context, the authors discuss the potential benefits, risks and impact of using Ad-derived vaccines to control Ebola virus disease.
Topics: AIDS Vaccines; Adenoviridae; Africa, Western; Clinical Trials as Topic; Drug Carriers; Drug Discovery; Drug Evaluation, Preclinical; Ebola Vaccines; Genetic Vectors; Hemorrhagic Fever, Ebola; Humans; Risk; Vaccines, Synthetic
PubMed: 26325242
DOI: 10.1586/14760584.2015.1083429