COVID-19 Vaccines, What do we know so Far? A Narrative Review

: For more than a year, the world was paralyzed by the COVID-19 pandemic. It wasn’t until the last few months that hope to a return of a quasi-normal way of living was starting to materialize. The era of the COVID-19 vaccines begun, and with it all sorts of concerns and complaints about their safety and efficacy. Large numbers of people believed the conspiracy theories about the new vaccines thus becoming reluctant and sometimes refused to take the new vaccines. Others justified their concern with the relatively short trial periods compared to previous vaccines that used to take years before adoption. Multiple vaccines emerged around the same time, and thus the fight to conquer the market began. Pfizer-BioNTech, Vaxzervria, Moderna, Sputnik, Coronavac, Janssen, all were rapidly distributed to countries around the globe, in order to reduce the mortality rate and control the pandemic. To make things worse, new viral mutations started being detected and thus shed more doubt on the efficacy of these vaccines.


INTRODUCTION
After more than a year of declaring COVID-19 a pandemic by the World Health Organization, there is no current curative treatment for SARS-CoV-2 and the numbers of mortalities and morbidities continue to rise [1] .Moreover, safety measures such as hygiene, lockdown and social distancing have not been proven to be enough in limiting the spread of the virus, therefore a rapid plan was implemented, and in less than a year, several vaccines against SARS-COV-2 have flooded the pharmaceutical market globally.
Governments and private firms have spent billions of dollars to develop vaccines within one year.Subsequently, several ones such as Pfizer-BioNTech, Moderna, and CoronaVac already approved by Food and Drug Association, and being distributed and hundreds of millions of people are inoculated so far [2] .As of February 2021, over two hundred million doses had been administered worldwide [2] , and countries, such as Israel and the United Kingdom, are making remarkable progress in immunizing their citizens.However, the vast majority of the rest of the world have only vaccinated small proportions of their populations and others are yet to start [2] .When this is not due to lack of available vaccines in developing countries, it could be the result of popular lack of confidence and fears from side effects of the rapidly approved vaccines [3] .
In fact, vaccines have globally been successful in limiting vaccine-preventable-diseases (VPD) and immunization, is the most effective strategy to inhibit spread of these diseases [4] , and in hope that this strategy will end the current pandemic, researchers are still studying the available vaccines, their correct usage, their safety and efficacy.
In this review, we discuss and describe the different vaccines, their mechanism of action, the international committees and association's recommendations about their use and safety in order to address readers' questions and concerns, especially those reluctant to get vaccinated.

PATHOPHYSIOLOGY AND MECHANISM OF ACTION
The currently available vaccines are believed to provide protection via neutralizing antibodies.Till this date, understanding the exact mechanisms by which antibodies confer this protection and induce such protective responses by the innate immune system is a key area of research [5] .The different available types are live attenuated vaccines that contain a weakened version of the living virus or bacteria, inactivated vaccines, toxoid vaccines, where toxins are weakened and injected into the body, subunit vaccines containing the essential antigen of the germs and conjugate vaccines that are effective against coated bacteria [5] .When it comes to COVID-19, new vaccination technologies have arisen, which differentiate them from one another.
The Chinese company Sinovac produced a coronavirus vaccine called CoronaVac.They used the Inactivated viruses' technique that have been used for over a century against several diseases.
After being injected in the body, the inactivated viruses are engulfed by immune cells called antigen presenting cells.The latter degrade the inactivated virus and display some of its protein on the surface of the cell [6] .B cells and Helper T cells identify the spike proteins.The immune cells get activated and proliferate antibodies against the antigen [7] .
The Pfizer-BioNTech and Moderna vaccines are manufactured using the messenger RNA (mRNA) technique and formulated as an RNA-lipid nanoparticle, nucleoside modified mRNA (modRNA).The mRNA or self-amplifying RNA (saRNA) are molecular templates that encode the antigen of interest, the spike protein [8,9] .After injection, the lipid nanoparticles (LPN) are absorbed by the cells while the mRNA is delivered into the cytosol where it is translated into the encrypted protein [8,9] .The spiked protein is displayed on the cell's surface, where they can be identified by the immune system, activating a response.This response involves cytotoxic T cells which kill infected cells, in addition to B cells and helper T cells, which produce and support antibodies production respectively [8,9] .
Instead of using mRNA, Vaxzervria, Sputnik V and Janssen vaccines, which are viral-vector based vaccines, use a double-stranded DNA [10,11,12] .The viral vector is a modified adenovirus that is stripped of any disease-causing genes to become a harmless virus [13] .Moreover, the researchers added the coronavirus spike protein gene to the viral vector which acts now as a delivery system, providing a mean to enter the cell and introduce the code of the targeted antigen.Once inside the cell, the modified virus enters to the nucleus, where the spike protein gene is copied into mRNA and then translated outside the nucleus to proteins.Consequently, the spike proteins migrate to the surface of the cells and trigger an immune response.B cells helper T cells as well as cytotoxic T cells are activated.To note, the adenovirus itself activate the immune system by turning on the cell's alarm system.By initiating this alarm, these vaccines trigger the immune system to act more powerf ully to the spike proteins [10,11,12] .

DOSING, SCHEDULE AND EFFICACY
Dosing and scheduling of the vaccines share some similarities.Pfizer-BioNTech is given intramuscularly for people 16 years and older, at 2 shots, given 3 weeks apart.Patient are fully vaccinated 2 weeks after the second shot [14] .Moderna also administered intramuscularly with 2 shots, given 4 weeks apart, and subjects get immunity also 2 weeks after the second dose, however it is recommended for people aged 18 years and older [14] .The Oxford-AstraZeneca vaccines, Vaxzervria, as found in most recent studies, shows top effectiveness when a person receives 2 doses, intramuscularly, 12 weeks apart [15] .Studies concerning Russian Sputnik V vaccine, show that in previously infected, the first dose elicits a strong humoral immune response that is even higher than that achieved after two doses in non-infected individuals [16] .Otherwise it should be administered in individuals of ≥ 18 years of age intramuscularly in two doses with interval of 21 days [17] .Moreover, studied concerning the Coronavac product encourage the use of 2 IM doses 14 days apart [18] ; and finally, after the resumption of J&J vaccines, the Center of Disease Control recommended the use of a single shot for adults 18 years or older [14] .Table : Vaccine Efficacy on Variants 19,20,21,22,23,24,25,26 Safety Profile and Side Effects Worldwide, people with and without scientific or medical backgrounds had concerns about vaccines 'safety and side effects.This prompted researchers and international committees in charge to constantly conduct trials, observational studies and issuing guidelines about the different vaccines adverse effects and safety profiles.

ISSN
In a randomized, double-blind, placebo-controlled study published in the Lancet journal in November 2020, entitled "Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19)" it was found that two doses of CoronaVac given at different concentrations or with different dosing schedules were well tolerated in people aged 18 to 59 years [27] .Furthermore, majority of side effects were mild, the most common symptom was pain at injection-site, which was similarly reported in previous studies regarding CoronaVac Vaccine.Very few patients reported fever as compared to other attenuated viral based vaccines.CoronaVac in this study was well tolerated and reported humoral responses against SARS-CoV-2 [27] .
Regarding the Pfizer-BioNTech vaccine, CDC stated that reactogenicity symptoms or side effects that happened within the first 7 days post vaccination were common but were mostly mild to moderate, based on several trials updated on April 16th, 2021.Also, concerning side effects such as fever, chills, lethargy and headaches, they were more common after the 2 nd dose [28].In a study