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[Research and application of the SARS-CoV-2 vaccine based on adenovirus vector technology platform].Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jul 2023During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have... (Review)
Review
During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.
Topics: Humans; COVID-19 Vaccines; Pandemics; COVID-19; SARS-CoV-2; Viral Vaccines; Adenoviridae; Technology
PubMed: 37198717
DOI: 10.3760/cma.j.cn112150-20230419-00309 -
Vaccines Jul 2014Viral vectors are promising tools for gene therapy and vaccines. Viral vector-based vaccines can enhance immunogenicity without an adjuvant and induce a robust cytotoxic... (Review)
Review
Viral vectors are promising tools for gene therapy and vaccines. Viral vector-based vaccines can enhance immunogenicity without an adjuvant and induce a robust cytotoxic T lymphocyte (CTL) response to eliminate virus-infected cells. During the last several decades, many types of viruses have been developed as vaccine vectors. Each has unique features and parental virus-related risks. In addition, genetically altered vectors have been developed to improve efficacy and safety, reduce administration dose, and enable large-scale manufacturing. To date, both successful and unsuccessful results have been reported in clinical trials. These trials provide important information on factors such as toxicity, administration dose tolerated, and optimized vaccination strategy. This review highlights major viral vectors that are the best candidates for clinical use.
PubMed: 26344749
DOI: 10.3390/vaccines2030624 -
Human Vaccines & Immunotherapeutics Jul 2018Adenoviral vector has been employed as one of the most efficient means against infectious diseases and cancer. It can be genetically modified and armed with foreign... (Review)
Review
Adenoviral vector has been employed as one of the most efficient means against infectious diseases and cancer. It can be genetically modified and armed with foreign antigens to elicit specific antibody responses and T cell responses in hosts as well as engineered to induce apoptosis in cancer cells. The chimpanzee adenovirus-based vector is one kind of novel vaccine carriers whose unique features and non-reactivity to pre-existing human adenovirus neutralizing antibodies makes it an outstanding candidate for vaccine research and development. Here, we review the different strategies for constructing chimpanzee adenoviral vectors and their applications in recent clinical trials and also discuss the oncolytic virotherapy and immunotherapy based on chimpanzee adenoviral vectors.
Topics: Adenoviruses, Human; Adenoviruses, Simian; Animals; Antibodies, Neutralizing; Antibodies, Viral; Cancer Vaccines; Clinical Trials as Topic; Genetic Vectors; Humans; Immunotherapy; Mice; Oncolytic Virotherapy; Pan troglodytes; T-Lymphocytes; Vaccines
PubMed: 29300685
DOI: 10.1080/21645515.2017.1419108 -
Antibody Therapeutics Jul 2022Additional COVID-19 vaccines that are safe and immunogenic are needed for global vaccine equity. Here, we developed a recombinant type 5 adenovirus vector encoding for...
Additional COVID-19 vaccines that are safe and immunogenic are needed for global vaccine equity. Here, we developed a recombinant type 5 adenovirus vector encoding for the SARS-CoV-2 S1 subunit antigen and nucleocapsid as a fusion protein (Ad5.SARS-CoV-2-S1N). A single subcutaneous immunization with Ad5.SARS-CoV-2-S1N induced a similar humoral response, along with a significantly higher S1-specific cellular response, as a recombinant type 5 adenovirus vector encoding for S1 alone (Ad5.SARS-CoV-2-S1). Immunogenicity was improved by homologous prime-boost vaccination, and further improved through intramuscular heterologous prime-boost vaccination using subunit recombinant S1 protein. Priming with low dose (1 × 10 v.p.) of Ad5.SARS-CoV-2-S1N and boosting with either wild-type recombinant rS1 or B.1.351 recombinant rS1 induced a robust neutralizing response, which was sustained against Beta and Gamma SARS-CoV-2 variants. This novel Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity in mice and supports the further development of COVID-19-based vaccines incorporating the nucleoprotein as a target antigen.
PubMed: 35967905
DOI: 10.1093/abt/tbac015 -
The Journal of Infectious Diseases Nov 2018
Topics: Adenoviridae; Adenovirus Vaccines; Ebola Vaccines; Ebolavirus; Hemorrhagic Fever, Ebola; Humans
PubMed: 29982527
DOI: 10.1093/infdis/jiy412 -
Expert Review of Vaccines Mar 2017Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated... (Review)
Review
Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.
Topics: Adenoviridae; Animals; Humans; Malaria; Malaria Vaccines; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit
PubMed: 27606709
DOI: 10.1080/14760584.2016.1228454 -
Viruses Aug 2022Chikungunya virus (CHIKV) is a mosquito-borne virus. The emergence of CHIKV infection has raised global concern, and there is a growing need to develop safe and...
Chikungunya virus (CHIKV) is a mosquito-borne virus. The emergence of CHIKV infection has raised global concern, and there is a growing need to develop safe and effective vaccines. Here, adenovirus 5 was used as the vaccine vector to construct recombinant adenoviruses expressing CHIKV E2, E1, and E2-6K-E1, respectively. And then the immunogenicity and protective efficiency against CHIKV were evaluated in BALB/c mice. Compared to the ad-wt control group, all three vaccines elicited significant humoral and cellar immune responses. The levels of neutralizing antibodies in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups both reached 1:256, which were 3.2 times higher than those in the rAd-CHIKV-E1 group. Furthermore, the levels of lymphocyte proliferation in rAd-CHIKV-E2-6K-E1 group were the highest. Besides, the concentrations of IFN-γ and IL-4 in mice immunized with rAd-CHIKV-E2-6K-E1 were 1.37 and 1.20 times higher than those in ad-wt immunized mice, respectively. After the challenge, mice in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups lost 2% of their body weight compared with 5% in the ad-wt control group. And low viral loads were detected in the heart, kidney, and blood of mice immunized with rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 at 3-5 dpc, which decreased by 0.4-0.7 orders of magnitude compared with the ad-wt control. Overall, these data suggest that the recombinant adenovirus is a potential candidate vaccine against CHIKV.
Topics: Adenoviridae; Adenoviridae Infections; Adenovirus Vaccines; Animals; Antibodies, Viral; Chikungunya Fever; Chikungunya virus; Mice; Mosquito Vectors; Vaccines, Synthetic; Viral Envelope Proteins; Viral Vaccines
PubMed: 36016401
DOI: 10.3390/v14081779 -
Journal of Virology Feb 2015Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in...
UNLABELLED
Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.
IMPORTANCE
Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens.
Topics: Adenoviridae; Adenoviridae Infections; Africa South of the Sahara; Animals; Antibodies, Viral; Cluster Analysis; DNA, Viral; Drug Carriers; Genetic Vectors; Humans; Macaca mulatta; Mice, Inbred BALB C; Molecular Sequence Data; Phylogeny; Sequence Analysis, DNA; Seroepidemiologic Studies; Vaccines, Synthetic
PubMed: 25410856
DOI: 10.1128/JVI.02950-14 -
Internal and Emergency Medicine Aug 2021The amazing effort of vaccination against COVID-19, with more than 2 billion vaccine doses administered all around the world as of 16 June 2021, has changed the history...
The amazing effort of vaccination against COVID-19, with more than 2 billion vaccine doses administered all around the world as of 16 June 2021, has changed the history of this pandemic, drastically reducing the number of severe cases or deaths in countries were mass vaccination campaign have been carried out. However, the people's rising enthusiasm has been blunted in late February 2021 by the report of several cases of unusual thrombotic events in combination with thrombocytopenia after vaccination with ChAdOx1 nCov-19 (Vaxzevria), and a few months later also after Ad26.COV2. S vaccines. Of note, both products used an Adenovirus-based (AdV) platform to deliver the mRNA molecule - coding for the spike protein of SARS-CoV-2. A clinical entity characterized by cerebral and/or splanchnic vein thrombosis, often associated with multiple thromboses, with thrombocytopenia and bleeding, and sometimes disseminated intravascular coagulation (DIC), was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). VITT was mainly observed in females under 55 years of age, between 4 and 16 days after receiving only Adenovirus-based vaccine and displayed a seriously high fatality rate. This prompted the Medicine Regulatory Agencies of various countries to enforce the pharmacovigilance programs, and to provide some advices to restrict the use of AdV-based vaccines to some age groups. This point-of view is aimed at providing a comprehensive review of epidemiological issues, pathogenetic hypothesis and treatment strategies of this rare but compelling syndrome, thus helping physicians to offer an up-to dated and evidence-based counseling to their often alarmed patients.
Topics: Biomarkers; COVID-19 Vaccines; Correlation of Data; Expert Testimony; Humans; Thrombocytopenia; Vaccination
PubMed: 34191218
DOI: 10.1007/s11739-021-02793-x -
Frontiers in Cardiovascular Medicine 2022COVID-19, the severe acute respiratory syndrome, is one of the major emergencies that have affected health care systems. Drugs and oxygen are only partially effective in... (Review)
Review
COVID-19, the severe acute respiratory syndrome, is one of the major emergencies that have affected health care systems. Drugs and oxygen are only partially effective in saving lives in patients with severe COVID-19, and the most important protection from death is vaccination. The widespread use of COVID-19 adenovirus-based vaccines has provided evidence for the occurrence of rare venous thrombotic events including cerebral venous thrombosis and splanchnic venous thrombosis in recipients of Vaxzevria and Jcovden vaccines and the review focus on them. One year ago, thromboses in Vaxzevria recipients have been associated with thrombocytopenia in the presence of antibodies to platelet factor 4 and have been called vaccine-induced immune thrombotic thrombocytopenia (VITT). The incidence of VITT is equal to 9-31 events per one million doses of vaccines as evaluated by health agencies worldwide and is higher in female and young vaccine recipients. More recently, by using the European EudraVigilance database, it has been demonstrated that the incidence of thrombosis in recipients of adenovirus-based vaccines is 5-10 fold higher than that of VITT and 7-12 fold higher than observed in the recipients of Comirnaty, an mRNA-based vaccine, suggesting that adenovirus-based vaccines cause not only VITT but also thrombosis without thrombocytopenia (non-VITT thrombosis). The incidence of the vaccine-dependent non-VITT thrombosis is different in the adenovirus-based vaccines and the VITT/non-VITT incidence ratio depends on the severity of thrombosis and is inversely related to the age of the recipients. The possible causes and clinical implications of non-VITT thrombosis in vaccine recipients are discussed.
PubMed: 36247442
DOI: 10.3389/fcvm.2022.967926