Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic

Abstract

Adenoviral vectors have been explored as vaccine agents for a range of infectious diseases, and their ability to induce a potent and balanced immune response made them logical candidates to apply to the COVID-19 pandemic. The unique molecular characteristics of these vectors enabled the rapid development of vaccines with advanced designs capable of overcoming the biological challenges faced by early adenoviral vector systems. These successes and the urgency of the COVID-19 situation have resulted in a flurry of candidate adenoviral vector vaccines for COVID-19 from both academia and industry. These vaccines represent some of the lead candidates currently supported by Operation Warp Speed and other government agencies for rapid translational development. This review details adenoviral vector COVID-19 vaccines currently in human clinical trials and provides an overview of the new technologies employed in their design. As these vaccines have formed a cornerstone of the COVID-19 global vaccination campaign, this review provides a full consideration of the impact and development of this emerging platform.

Fig. 1. Adenovirus structure organization and interaction with host cell.

a Adenovirus is a dsDNA, non-enveloped virus mainly composed by the structural protein, hexon, and other components associated with its interaction with the host cells (penton base and knobbed fiber). b The early stage of the infection cycle is marked by the knob domain of the viral fiber interaction with the Coxsackie and Adenovirus Receptor (CAR), followed by the penton-base with αvβ integrins present in the cell surface. CAR is the main receptor for the adenovirus serotype 5, however other serotypes utilize different receptors for cell entry.

Fig. 2. Coronavirus structure and relevant aspects for vaccine development.

a Current vaccines are capitalizing in epitopes present in the SARS-CoV-2 proteins to elicit an immune responses. The major proteins used for vaccine development are the nucleocapsid, and the spike protein, essential for cell entry. b Spike protein can have conformation modifications protease-mediated. The stabilization of the protein in its prefusion form improves the protein expression as well as immunogenicity.