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      A focused review on technologies, mechanisms, safety, and efficacy of available COVID-19 vaccines

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          Abstract

          More than 20 months has been passed since the detection of the first cases of SARS-CoV-2 infection named COVID-19 from Wuhan city of China. This novel coronavirus spread rapidly around the world and became a pandemic. Although different therapeutic options have been considered and approved for the management of COVID-19 infection in different stages of the disease, challenges in pharmacotherapy especially in patients with moderate to severe COVID-19 and with underlying diseases have still remained. Prevention of infection through public vaccination would be the only efficient strategy to control the morbidity and mortality caused by COVID-19. To date, several COVID-19 vaccines using different platforms including nucleic acid-based vaccines, adenovirus-based vaccines, protein-based vaccines, and inactivated vaccines have been introduced among which many have received approval for prevention against COVID-19. In this comprehensive review, available COVID-19 vaccines have been discussed. The mechanisms, safety, efficacy, dosage, dosing intervals, possible adverse reactions, storage, and coverage of these four different vaccine platforms against SARS-CoV-2 variants have been discussed in detail and summarized in tabular format for ease of comparison and conclusion. Although each COVID-19 vaccine has various advantages and disadvantages over the others, accessibility and affordability of approved vaccines by the official health organizations, especially in developing countries, would be essential to terminate this pandemic. The main limitation of this study was the lack of access to the clinical data on available COVID-19 vaccines developed in Eastern countries since the data on their efficacy, safety, and adverse reactions were limited.

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          An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

          Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. Methods We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. Results After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. Conclusions The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).
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            mRNA vaccines — a new era in vaccinology

            mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
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              Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

              Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. Methods In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. Results A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. Conclusions The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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                Author and article information

                Journal
                Int Immunopharmacol
                Int Immunopharmacol
                International Immunopharmacology
                Published by Elsevier B.V.
                1567-5769
                1878-1705
                17 September 2021
                17 September 2021
                : 108162
                Affiliations
                [a ]Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
                [b ]Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
                [c ]Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
                [d ]Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
                [e ]Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
                Author notes
                [* ]Corresponding author.at: Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
                [1]

                School of Pharmacy, Shiraz-Marvdasht Hwy, Karafarin St, Shiraz, Fars Province 71468 64685, Iran.

                Article
                S1567-5769(21)00798-0 108162
                10.1016/j.intimp.2021.108162
                8445802
                34562844
                369b6b69-e55a-4cfd-8836-a5a2aedf9fb2
                © 2021 Published by Elsevier B.V.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 16 June 2021
                : 12 September 2021
                : 14 September 2021
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                covid-19,sars-cov-2,nucleic acid-based vaccines,viral vector vaccines,protein-based vaccines,inactivated vaccines

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