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Techniques for Developing and Assessing Immune Responses Induced by Synthetic DNA Vaccines for Emerging Infectious Diseases

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Vaccine Design

Abstract

Vaccines are one of mankind’s greatest medical advances, and their use has drastically reduced and in some cases eliminated (e.g., smallpox) disease and death caused by infectious agents. Traditional vaccine modalities including live-attenuated pathogen vaccines, wholly inactivated pathogen vaccines, and protein-based pathogen subunit vaccines have successfully been used to create efficacious vaccines against measles, mumps, rubella, polio, and yellow fever. These traditional vaccine modalities, however, take many months to years to develop and have thus proven less effective for use in creating vaccines to emerging or reemerging infectious diseases (EIDs) including influenza, Human immunodeficiency virus (HIV), dengue virus (DENV), chikungunya virus (CHIKV), West Nile virus (WNV), Middle East respiratory syndrome (MERS), and the severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV and SARS-CoV-2). As factors such as climate change and increased globalization continue to increase the pace of EID development, newer vaccine modalities are required to develop vaccines that can prevent or attenuate EID outbreaks throughout the world. One such modality, DNA vaccines, has been studied for over 30 years and has numerous qualities that make them ideal for meeting the challenge of EIDs including; (1) DNA vaccine candidates can be designed within hours of publishing of a pathogens genetic sequence; (2) they can be manufactured cheaply and rapidly in large quantities; (3) they are thermostable and have reduced requirement for a cold-chain during distribution, and (4) they have a remarkable safety record in the clinic. Optimizations made in plasmid design as well as in DNA vaccine delivery have greatly improved the immunogenicity of these vaccines. Here we describe the process of making a DNA vaccine to an EID pathogen and describe methods used for assessing the immunogenicity and protective efficacy of DNA vaccines in small animal models.

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Acknowledgments

K.M. is supported by Wistar-Discovery fund and W.W. Smith Charitable Trust grant #H1905. He has a patent application for DNA vaccine development and delivery of DNA-encoded monoclonal antibodies. M.A-M is supported by NIH grants (R01 DK123733, R01 AG062383, R01 NS117458, R21 AI143385, R21 AI129636, and R21 NS106970), The Foundation for AIDS Research (amfAR) impact grant #109840-65-RGRL, and W.W. Smith Charitable Trust grant #A1901. The other authors declare no competing financial interests.

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Xu, Z. et al. (2022). Techniques for Developing and Assessing Immune Responses Induced by Synthetic DNA Vaccines for Emerging Infectious Diseases. In: Thomas, S. (eds) Vaccine Design. Methods in Molecular Biology, vol 2410. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1884-4_11

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  • DOI: https://doi.org/10.1007/978-1-0716-1884-4_11

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