SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

Nikolaos C Kyriakidis, Andrés López-Cortés, Eduardo Vásconez González, Alejandra Barreto Grimaldos, Esteban Ortiz Prado, Nikolaos C Kyriakidis, Andrés López-Cortés, Eduardo Vásconez González, Alejandra Barreto Grimaldos, Esteban Ortiz Prado

Abstract

The new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Most advanced SARS-CoV-2 vaccine candidates.
Fig. 1. Most advanced SARS-CoV-2 vaccine candidates.
The vaccine candidates are grouped according to the platform technology used for their development: mRNA vaccines, replication-defective viral vector vaccines, inactivated pathogen vaccines, protein subunit vaccines, and virus-like vaccines. Manufacturer name, Phase 3 trial data, immunogenicity and current status information are herein detailed. EMA European Medicines Agency, UK The United Kingdom, US The United States, UEA United Arab Emirates.
Fig. 2. Overview of the strategies used…
Fig. 2. Overview of the strategies used for vaccine development and delivery.
A Attenuated live pathogen vaccine strategies consist in administering a debilitated form of live pathogen. Lengthy cell culture passaging in non-human cell lines or animals decreases the virulence of the pathogen. This type of vaccines usually elicits robust and long-term memory immune responses after a single dose. B Inactivated pathogen vaccines contain whole pathogen that has been submitted to heat or chemical treatment inactivation. C Subunit vaccines are prepared either from antigen purification of pathogens replicated in cell cultures or from recombinantly expressed antigens. These vaccines commonly require adjuvant addition in order to deliver danger signals to antigen-presenting cells and provoke robust immune responses. D Virus-like particles can be self-assembled in and released from recombinant yeast cells or other expression systems such as the vaccinia virus expression system or even tobacco plants transfected with tobacco mosaic virus. E Viral vector vaccines use a genetically manipulated measles or adenoviral platform to express a foreign antigen commonly resulting in robust cellular and humoral response. F, G Lastly, nucleic acid (DNA and mRNA) vaccines are very quick to produce, yet were untested as successful human vaccine strategies. The nucleic acid codifying for an immunogenic protein of the pathogen once administered is captured by antigen-presenting cells that use it to express and present the antigen. These vaccines are predicted to have minor safety issues as nucleic acid is swiftly degraded within the human body.

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