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

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 proteinbased 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.

Live-Attenuated VEEV Vaccine Delivered by iDNA Using Microneedles Is Immunogenic in Rabbits

“…Efficient vaccination with DNA vaccines remains among the most important goals of current vaccinology (18)(19)(20). Although shown safe and effective in animal models, standard DNA vaccines demonstrate limited success in humans and sometimes require large doses, multiple booster vaccinations, advanced adjuvants, novel formulations, and/or complex delivery equipment including in vivo electroporation.…”

Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection

“…To prepare the run, labeled and purified glycans were spiked in with GeneScan 600 LIZ size standard (Thermo Fisher; catalog# 4408399) to ensure consistent peak heights and to provide consistent results between different injections and capillaries. The N -glycans were analyzed using the 3500 Genetic Analyzer capillary electrophoresis system, as detailed in a previous publication 99 . Each sample was run in a single well, and samples were added to the machine in batches of 96 samples in a random order.…”