UMMS Affiliation

Horae Gene Therapy Center; VIDE Program; Department of Microbiology and Physiological Systems; Li Weibo Institute for Rare Diseases Research

Publication Date

2021-05-11

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Immunotherapy | Viruses

Abstract

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.

Keywords

adeno-associated virus, gene therapy, immunotherapy, vaccines, vectors

Rights and Permissions

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.

DOI of Published Version

10.3389/fimmu.2021.673699

Source

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. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in immunology

Related Resources

Link to Article in PubMed

PubMed ID

34046041

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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