An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times

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Abstract

Since the worldwide COVID-19 pandemic was declared a year ago, the search for vaccines has become the top priority in order to restore normalcy after 2.5 million deaths worldwide, overloaded sanitary systems, and a huge economic burden. Vaccine development has represented a step towards the desired herd immunity in a short period of time, owing to a high level of investment, the focus of researchers, and the urge for the authorization of the faster administration of vaccines. Nevertheless, this objective may only be achieved by pursuing effective strategies and policies in various countries worldwide. In the present review, some aspects involved in accomplishing a successful vaccination program are addressed, in addition to the importance of vaccination in a pandemic in the face of unwillingness, conspiracy theories, or a lack of information among the public. Moreover, we provide some updated points related to the landscape of the clinical development of vaccine candidates, specifically, the top five vaccines that are already being assessed in Phase IV clinical trials (BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, and CoronaVac).

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Most cited references 165

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Roujian Lu, Xiang Zhao, Juan Li … (2021)

Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

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Contributors

Ralph A. Tripp: Role: Academic Editor

Journal

Journal ID (nlm-ta): Vaccines (Basel)

Journal ID (iso-abbrev): Vaccines (Basel)

Journal ID (publisher-id): vaccines

Title: Vaccines

Publisher: MDPI

ISSN (Electronic): 2076-393X

Publication date (Electronic): 27 April 2021

Publication date Collection: May 2021

Volume: 9

Issue: 5

Electronic Location Identifier: 433

Affiliations

[1 ]Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain; cielogar@ 123456ucm.es (C.G.-M.); oscar.fraile@ 123456edu.uah.es (O.F.-M.); lstrujillo@ 123456salud.madrid.org (L.S.-T.); anam.gomez@ 123456uah.es (A.M.G.-L.); natalio.garcia@ 123456uah.es (N.G.-H.); mjulia.bujan@ 123456uah.es (J.B.); jorge.monserrat@ 123456uah.es (J.M.); mademons@ 123456uah.es (M.Á.-M.); maalvarez.gonzalez@ 123456salud.madrid.org (M.A.Á.-M.); miguelangel.ortega@ 123456edu.uah.es (M.A.O.)

[2 ]Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; coral.bravo@ 123456salud.madrid.org

[3 ]Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain

[4 ]Health Research Institute Gregorio Marañón, 28009 Madrid, Spain

[5 ]First of May Health Centre, Health Area I, Rivas Vaciamadrid, 28521 Madrid, Spain; dtorresc@ 123456salud.madrid.org

[6 ]Service of Pediatric, Hospital Universitario Principe de Asturias, 28801 Alcalá de Henares, Spain

[7 ]Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of System Biology, University of Alcalá, 28801 Alcalá de Henares, Spain; luis.gonzalez@ 123456uah.es

[8 ]Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; angel.asunsolo@ 123456uah.es

[9 ]Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain

[10 ]Los fresnos of Health Centre, Health Area III, Torrejon de Ardoz, 28850 Madrid, Spain; encarnacion.serrano@ 123456uah.es

[11 ]Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine, University Hospital Príncipe de Asturias, (CIBEREHD), 28806 Alcalá de Henares, Spain

[12 ]Department of Psychiatry and Medical Psychology, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain

[13 ]Cancer Registry and Pathology Department, Hospital Universitario Principe de Asturias, 28806 Alcalá de Henares, Spain

Author notes

[* ]Correspondence: jaleon@ 123456ucm.es

Author information

Cielo García-Montero https://orcid.org/0000-0001-6016-7855

Lara Sanchez-Trujillo https://orcid.org/0000-0002-0908-7566

Angel Asúnsolo https://orcid.org/0000-0001-7898-4685

Julia Bujan https://orcid.org/0000-0003-2419-2476

Jorge Monserrat https://orcid.org/0000-0003-1775-4645

Miguel A. Álvarez-Mon https://orcid.org/0000-0002-1987-0394

Miguel A. Ortega https://orcid.org/0000-0003-2588-1708

Article

Publisher ID: vaccines-09-00433

DOI: 10.3390/vaccines9050433

PMC ID: 8146241

PubMed ID: 33925526

SO-VID: 09e3c9e7-8901-4525-93fc-91de8882fbac

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times

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Novel Coronavirus Disease COVID-19

Most cited references 165

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

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