A review on how exactly covid-19 vaccination works

The Coronavirus pandemic has taken the world by storm, covering the entire year of 2020. In order to put an end to the pandemic many organizations around the world are racing to find a safe and effective vaccine. Today, newer technology of nucleic acid vaccine has been use to create a novel vaccine for novel coronavirus. Many countries like the United States of America, United Kingdom and even Russia and China have successfully developed approved vaccines. But there remains a doubt of uncertainty among people regarding how fast this vaccine was created when compared to others which have taken years. This review aims to highlight and summarize the ongoing process and development in making Covid vaccines.


Introduction
The Covid-19 pandemic has become a landmark of the years 2019 and 2020 and probably even the 21 st century. As we race to find a cure to this deadly viral disease, many questions arise along the way. For it will be the first vaccine to be developed in matter of months and one of among the few against an RNA virus which is susceptible to frequent mutations. If the vaccine is successful, then it is possible to develop a vaccine against the HIV virus which cause AIDS and maybe even the Rhinovirus causing common cold.

Background of pathogen-SARS-CoV-2
The nCovid-19 is caused by SARS-CoV-2 virus which belongs to family Coronaviridae in the order Nidovirales with its genome as ssRNA [1,2]. So far, out of 100 strains of coronavirus,7 of them have been identified which are known to infect humans. Three of which viz. SARS-1, MERS and the recent SARS-CoV-2 have caused fatal respiratory infection in humans while the other four only lead to common cold [3].
The new variant of SARS-CoV-2, first reported by Britain is called VUI-202012/01 (the first "Variant Under Investigation" in December 2020) [4]. It has undergone 17 set of mutation and makes it 70% more transmissible [4].

Mutations
Mutation such as these happen to all living organism. But being an RNA virus makes the rate faster. As a result, the HIV virus mutates at a rate of (4.1 ± 1.7) × 10 −3 per base per cell, causing it bypass host immune system [5]. Thus, making it increasingly difficult to tract its changes and make suitable vaccine. Although, antiviral drugs fairly keep the viral load suppressed inside the body. Similarly, the Rhinoviruses has a mutation rate of 10 −3 to 10 −5 mutations per base per replication event [6]. The same can be applied for influenza virus causing the flu.
But the RNA-dependent RNA polymerase (RdRp) which is the main enzyme for viral genome replication has a characteristic feature of proofreading in SARS-CoV-2 [7]. Therefore, making its rate of mutation appreciably less when compared to other ssRNA viruses. Hence making it possible to find its vaccine.
The coronavirus and influenza virus share much in common. Studies show that influenza virus undergo broadly two types of mutation; Antigenic Drift and Antigenic Shift. But due to four time slower mutation rate of coronavirus than the influenza virus, it has not yet undergone antigenic drift. This provides longer immunity from a vaccine than the flu vaccine which is taken every six months [19].

Structure of Coronavirus
When producing a vaccine, researches mainly focus only on one specific components of the pathogen that the immunity has to develop against. With experience from previous pandemics such as SARS-CoV-1 and MERS, the only component to be identified here for SARS-CoV-2 vaccine is the characteristic spike protein(S-protein). Show in Figure 1. The S-protein of virus is used in binding to ACE-2(angiotensin converting enzyme-2) receptor found on lung mucosa and GI tract. By blocking this protein through human body's antibodies,t virus can no longer infect the human cells. Thus giving protection against coronavirus.

How Vaccination works
Vaccines are infusion of artificial substance that prepare the body against deadly pathogens. Therefore, when it actually encounters the pathogen the infection produced are much milder and restores health faster.

Vector based vaccine-adenovirus
The use of human adenoviruses as vectors is safe as these viruses simply cause the common cold and successful treatments are available if infection is caused by the adenovirus. [12] Example; Oxford AstraZeneca and Sputnik-V [10]

Protein subunit vaccine
The protein subunits of virus, usually the main spike proteins are injected into the body. But since the immune system cannot recognize them effectively, adjuvants are used.

Genetic vaccine
mRNA vaccine -latest and very new technique  highest efficacy and efficiency rate  Major problem in storage condition;  The mRNA is prone to degradation at room temperature. Moderna's vaccine is stored at -20 degree Celsius (-4 degrees Fahrenheit), or at refrigerator temperatures for up to 30 days, while the Pfizer vaccine has to be stored at an ultra-cold temperature of -75˚C (-103˚F), and used within five days once refrigerated at higher temperatures [15].

DNA vaccines
Deoxy ribose nucleic acid vaccine using gene gun technology. But it still requires much development.

Russia
The Russians organization Gamaleya Research Institute of Epidemiology and Microbiology developed Gam-COVID-Vac trade-named or commonly called Sputnik V registered on 11 August 2020 by the Russian Ministry of Health [15]. It was the first vaccine in the world to be approved for public distribution by the Russian Government [13]. It is a vector based human adenovirus vaccine. Here, two different types of adenovirus vectors (rAd26 and rAd5) were used for the first and second vaccination enabling the boosting effect of the vaccine. Efficacy of the vaccine is said to be about 91% to 100% in severe Covid cases [12] The vaccine was financed by Russian Direct Investment Fund (RDIF) for the production of the Sputnik V, on the basis of production capacities of its portfolio companies, R-Pharm and Binnopharm, a part of the Alium Group [10,12].

China
The companies that developed the Chinese vaccines are; CanSino Biologics, Sinovac Biotech and Sinopharm. China approved its first COVID-19 vaccine for distribution Thursday December 31 developed by Sinopharm. The Vaccine has shown 86% efficacy, as reported by the United Arab Emirates Health Ministry, one of the countries where phase 3 trial was conducted [15].But according to the developer, the vaccine showed 79.34 per cent efficacy based on an interim analysis of late-stage clinical trials [16].

COVAX
Coordinated by Gavi, the Vaccine Alliance, the Coalition for Epidemic Preparedness Innovations (CEPI) and the WHO. COVAX acts as a platform that supports research, development and manufacturing of authentic and secure COVID-19 vaccine candidates, and negotiate their pricing. The main goal of this organization is to provide all participating countries regardless of income levels equitable access to these vaccines [24].

Preclinical trials
Done in suitable animals or human cells in vitro. It determines the working of vaccine and takes the longest time in vaccine trial process. Includes;  PittCoVacc-Recombinant protein subunit vaccine; University of Pittsburgh.

Clinical Studies
All the clinical phases of trial consist of human volunteers with vaccine administration to one group and placebo control of other. This set up is done to compare and study the effect of vaccine in administered vs placebo volunteers.

Phase 1
Vaccines are given to small group of human volunteers limited to about 10 to 50 in number. It determines the safety of vaccine and may take few months.

Phase 2
Vaccine is administered to medium group of individuals consisting of several hundred volunteers of various age groups. It determines the working and may take few months to years.

Includes;
 Protein subunit vaccine-Sanofi and GlaxoSmithKlein

Phase 3
Vaccine administered to large size group including thousands of volunteers of diverse background in age, sex, race and ethnicity. It determines its effectiveness which usually takes years to complete.

Approved Vaccines
The data is obtained from phase 2 and phase 3 trials is analyzed and evaluated by the authorities which then get their approval for licensing and further manufacturing and distribution to the public. Includes;

Side Effect of Vaccines
The focus is mainly on Pfizer and Moderna as these two have been approved all around the world.

Pfizer vaccine
Safety monitoring of Pfizer vaccine will continue for 2 years after administration of the second dose [20].

Adverse effect
 4 cases of Bell's palsy were observed but these are number are same for chances of occurrence in normal condition without vaccine administration.  Allergic reaction equivalent to anaphylactic reaction observed in healthcare workers after administration of vaccine  No deaths were reported by the investigators to be related to the vaccine or placebo. No Covid-19-associated deaths were observed.

Moderna [21]
 pain at the injection  fatigue  headache  fever and chills  nausea  myalgia

Who will get the vaccine first?
The first few doses of vaccine are being prioritized for frontline worker including medical and paramedical workers and those in vulnerable groups such as the elderly, or people living in crowded settings, and individuals with multiple existing conditions, such as serious heart diseases or diabetes. Workers in essential industries, such as in public transport or the jobs requiring them to meet large number of people such as prisons are also given priority [26].

Herd Immunity-a brief concept
It is referred to as "the resistance of a group against the attack of a disease because large proportion of its members being immune to it which decreases the likelihood of an affected individual transmitting it to other individuals" [22]. This indicates that is not necessary for a given population to be 100% vaccinated. Those at high risk or most vulnerable, if vaccinated reduces the transmission rate of infection. This also reduces the chance of spreading the disease from an affected individual to susceptible individual. Thereby effectively reducing the efficiency of microbe to survive, especially those which depend to person to person transmission. Therefore, it is easily controlled and disappears at some level of vaccine coverage over a period of time [23].

Conclusion
To conclude, vaccination is necessary to tackle the spread of pandemic and save the life of millions around the globe. Thanks to the new innovation in technology, we have been able to dive deep into the very core of virus and find a weak spot in its structure. But we have to keep in mind that not all the people on earth may get or require vaccine. Hence the new coronavirus norms have to be followed until the virus has disappeared completely.