The Coming of Age of Nucleic Acid Vaccines during COVID-19

Abstract

In the 21st century, several emergent viruses have posed a global threat. Each pathogen has emphasized the value of rapid and scalable vaccine development programs. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made the importance of such efforts especially clear. New biotechnological advances in vaccinology allow for recent advances that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns. During the COVID-19 pandemic, these DNA and RNA vaccines have facilitated the development and deployment of vaccines at an unprecedented pace. This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics: the genome of SARS-CoV-2 was available as early as January 2020, facilitating global efforts in the development of DNA and RNA vaccines within 2 weeks of the international community becoming aware of the new viral threat. Additionally, these technologies that were previously only theoretical are not only safe but also highly efficacious. Although historically a slow process, the rapid development of vaccines during the COVID-19 crisis reveals a major shift in vaccine technologies. Here, we provide historical context for the emergence of these paradigm-shifting vaccines. We describe several DNA and RNA vaccines in terms of their efficacy, safety, and approval status. We also discuss patterns in worldwide distribution. The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last 2 decades in particular and suggest a new era in vaccines against emerging pathogens. IMPORTANCE The SARS-CoV-2 pandemic has caused untold damage globally, presenting unusual demands on but also unique opportunities for vaccine development. The development, production, and distribution of vaccines are imperative to saving lives, preventing severe illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Although vaccine technologies that provide the DNA or RNA sequence of an antigen had never previously been approved for use in humans, they have played a major role in the management of SARS-CoV-2. In this review, we discuss the history of these vaccines and how they have been applied to SARS-CoV-2. Additionally, given that the evolution of new SARS-CoV-2 variants continues to present a significant challenge in 2022, these vaccines remain an important and evolving tool in the biomedical response to the pandemic.

Keywords: COVID-19; DNA vaccines; SARS-CoV-2; mRNA vaccines; nucleic acid vaccines; review; vaccine equity; vaccines.

FIG 1

Structure of SARS-CoV-2. The development of vaccines depends on the immune system recognizing the virus. Here, the structure of SARS-CoV-2 is represented both in the abstract and against a visualization of the virion. The abstracted visualization was made using BioRender (https://biorender.com) using the template “Human Coronavirus Structure” by BioRender (August 2020) (234). The microscopy was conducted by the National Institute of Allergy and Infectious Diseases (235).

FIG 2

Worldwide availability of vaccines developed using nonreplicating viral vectors. This figure reflects the number of vaccines using nonreplicating viral vectors that were available in each country as of 9 October 2022. These data were retrieved from Our World in Data (70) and plotted using geopandas (236). See https://greenelab.github.io/covid19-review/ for the most recent version of this figure, which is updated daily. Note that this figure draws from a different data source than Table 1 and does not necessarily include data for every vaccine developed within this category.

FIG 3

Worldwide availability of vaccines developed using mRNA. This figure reflects the number of vaccines based on mRNA technology that were available in each country as of 9 October 2022. These data are retrieved from Our World in Data (70) and plotted using geopandas (236). See https://greenelab.github.io/covid19-review/ for the most recent version of this figure, which is updated daily. Note that this figure draws from a different data source than Table 2 and does not necessarily include data for every vaccine developed within this category.