SARS-CoV-2 Vaccine Development: Current Status

Abstract

In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic and its attendant morbidity and mortality, safe and efficacious vaccines are needed that induce protective and long-lived immune responses. More than 120 vaccine candidates worldwide are in various preclinical and phase 1 to 3 clinical trials that include inactivated, live-attenuated, viral-vectored replicating and nonreplicating, protein- and peptide-based, and nucleic acid approaches. Vaccines will be necessary both for individual protection and for the safe development of population-level herd immunity. Public-private partnership collaborative efforts, such as the Accelerating COVID-19 Therapeutic Interventions and Vaccines mechanism, are key to rapidly identifying safe and effective vaccine candidates as quickly and efficiently as possible. In this article, we review the major vaccine approaches being taken and issues that must be resolved in the quest for vaccines to prevent coronavirus disease 2019. For this study, we scanned the PubMed database from 1963 to 2020 for all publications using the following search terms in various combinations: SARS, MERS, COVID-19, SARS-CoV-2, vaccine, clinical trial, coronavirus, pandemic, and vaccine development. We also did a Web search for these same terms. In addition, we examined the World Health Organization, Centers for Disease Control and Prevention, and other public health authority websites. We excluded abstracts and all articles that were not written in English.

Figure

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A, Diagram of the SARS-CoV-2 virion, including the lipid membrane and structural proteins. B, The 4 major structural proteins are targeted by immune response. Humoral responses are directed at both the spike protein and the nucleocapsid proteins. Neutralizing antibodies have been identified that target the receptor-binding domain of the spike protein. All of the structural (and many of the nonstructural) proteins have predicted T-cell epitopes within them, suggesting that the T-cell response is likely able to recognize most viral proteins. C, Representation of the major types of SARS-CoV-2 vaccines under development. Live-virus vaccines typically consist of a weakened version of the virus, while whole inactivated vaccines use chemicals or radiation to eliminate viral replication. Vector-based vaccines incorporate one or more viral genes (in red) into the genome of a viral vector. Some vectors are replicating (eg, measles), while others may be replication-defective but are capable of limited transcription and expression of the desired coronavirus antigen. Subunit vaccines typically consist of specific viral proteins or immunogenic peptides derived from those proteins. Nucleic acid vaccines contain DNA (top figure) or RNA (bottom figure) that are delivered using electroporation or liposomal delivery systems that enable the nucleic acid to enter target cells. Viral protein is then produced by the host cells.