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dc.contributor.authorZhan, Wei
dc.contributor.authorMuhuri, Manish
dc.contributor.authorTai, Phillip W. L.
dc.contributor.authorGao, Guangping
dc.date2022-08-11T08:10:00.000
dc.date.accessioned2022-08-23T16:51:47Z
dc.date.available2022-08-23T16:51:47Z
dc.date.issued2021-05-11
dc.date.submitted2021-09-02
dc.identifier.citation<p>Zhan W, Muhuri M, Tai PWL, Gao G. Vectored Immunotherapeutics for Infectious Diseases: Can rAAVs Be The Game Changers for Fighting Transmissible Pathogens? Front Immunol. 2021 May 11;12:673699. doi: 10.3389/fimmu.2021.673699. PMID: 34046041; PMCID: PMC8144494. <a href="https://doi.org/10.3389/fimmu.2021.673699">Link to article on publisher's site</a></p>
dc.identifier.issn1664-3224 (Linking)
dc.identifier.doi10.3389/fimmu.2021.673699
dc.identifier.pmid34046041
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41925
dc.description.abstractConventional vaccinations and immunotherapies have encountered major roadblocks in preventing infectious diseases like HIV, influenza, and malaria. These challenges are due to the high genomic variation and immunomodulatory mechanisms inherent to these diseases. Passive transfer of broadly neutralizing antibodies may offer partial protection, but these treatments require repeated dosing. Some recombinant viral vectors, such as those based on lentiviruses and adeno-associated viruses (AAVs), can confer long-term transgene expression in the host after a single dose. Particularly, recombinant (r)AAVs have emerged as favorable vectors, given their high in vivo transduction efficiency, proven clinical efficacy, and low immunogenicity profiles. Hence, rAAVs are being explored to deliver recombinant antibodies to confer immunity against infections or to diminish the severity of disease. When used as a vaccination vector for the delivery of antigens, rAAVs enable de novo synthesis of foreign proteins with the conformation and topology that resemble those of natural pathogens. However, technical hurdles like pre-existing immunity to the rAAV capsid and production of anti-drug antibodies can reduce the efficacy of rAAV-vectored immunotherapies. This review summarizes rAAV-based prophylactic and therapeutic strategies developed against infectious diseases that are currently being tested in pre-clinical and clinical studies. Technical challenges and potential solutions will also be discussed.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34046041&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2021 Zhan, Muhuri, Tai and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectadeno-associated virus
dc.subjectgene therapy
dc.subjectimmunotherapy
dc.subjectvaccines
dc.subjectvectors
dc.subjectImmunology of Infectious Disease
dc.subjectImmunoprophylaxis and Therapy
dc.subjectImmunotherapy
dc.subjectViruses
dc.titleVectored Immunotherapeutics for Infectious Diseases: Can rAAVs Be The Game Changers for Fighting Transmissible Pathogens?
dc.typeJournal Article
dc.source.journaltitleFrontiers in immunology
dc.source.volume12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5763&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4730
dc.identifier.contextkey24636130
refterms.dateFOA2022-08-23T16:51:48Z
html.description.abstract<p>Conventional vaccinations and immunotherapies have encountered major roadblocks in preventing infectious diseases like HIV, influenza, and malaria. These challenges are due to the high genomic variation and immunomodulatory mechanisms inherent to these diseases. Passive transfer of broadly neutralizing antibodies may offer partial protection, but these treatments require repeated dosing. Some recombinant viral vectors, such as those based on lentiviruses and adeno-associated viruses (AAVs), can confer long-term transgene expression in the host after a single dose. Particularly, recombinant (r)AAVs have emerged as favorable vectors, given their high in vivo transduction efficiency, proven clinical efficacy, and low immunogenicity profiles. Hence, rAAVs are being explored to deliver recombinant antibodies to confer immunity against infections or to diminish the severity of disease. When used as a vaccination vector for the delivery of antigens, rAAVs enable de novo synthesis of foreign proteins with the conformation and topology that resemble those of natural pathogens. However, technical hurdles like pre-existing immunity to the rAAV capsid and production of anti-drug antibodies can reduce the efficacy of rAAV-vectored immunotherapies. This review summarizes rAAV-based prophylactic and therapeutic strategies developed against infectious diseases that are currently being tested in pre-clinical and clinical studies. Technical challenges and potential solutions will also be discussed.</p>
dc.identifier.submissionpathoapubs/4730
dc.contributor.departmentLi Weibo Institute for Rare Diseases Research
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.contributor.departmentVIDE Program
dc.contributor.departmentHorae Gene Therapy Center
dc.source.pages673699


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Copyright © 2021 Zhan, Muhuri, Tai and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Except where otherwise noted, this item's license is described as Copyright © 2021 Zhan, Muhuri, Tai and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.