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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 1  |  Page : 50-53

A review on COVID-19 vaccinations


1 Department of Pathology, Jyoti Gupta Clinic, New Delhi, India
2 Department of Medicine, Talwar nursing home, Sirsa, Haryana, India
3 Department of Research, Graduate School of Bio-medical and Health Sciences at Hiroshima University, Japan
4 Department of Endocrinology, Safdarjung hospital, New Delhi, India
5 Department of Medicine, Baroda Medical College, Vadodara, India
6 Department of Medicine, Pramukhswami Medical College, New Delhi, India
7 Department of Biostatistics, Jyoti Gupta Clinic, New Delhi, India

Date of Submission21-Oct-2021
Date of Acceptance16-Dec-2021
Date of Web Publication11-Mar-2022

Correspondence Address:
Ketan Garg
Jyoti Gupta Clinic, New Delhi - 110 017
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_280_21

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  Abstract 


The year 2019 witnessed a pandemic named COVID-19 caused by infection severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It emerged in Wuhan, China, in December 2019 and has affected millions since then. It led to a global cry for vaccine development. Scientists arrayed the SARS-CoV-2 genome within a month of the outbreak. They used the parallels between SARS-CoV-1 and SARS-CoV-2 to speed up the vaccine preparation. As of now, different types of COVID-19 vaccines are prevailing.

Keywords: COVID-19, mRNA, vaccines


How to cite this article:
Garg K, Talwar D, Mahajan SN, Karim S, Prajapati K, Patel S, Garg B. A review on COVID-19 vaccinations. Biomed Biotechnol Res J 2022;6:50-3

How to cite this URL:
Garg K, Talwar D, Mahajan SN, Karim S, Prajapati K, Patel S, Garg B. A review on COVID-19 vaccinations. Biomed Biotechnol Res J [serial online] 2022 [cited 2022 Oct 1];6:50-3. Available from: https://www.bmbtrj.org/text.asp?2022/6/1/50/339379




  Types of Vaccines and Their Mechanism of Action Top


The vaccines are based on live attenuated or inactivated viruses, viral vectors (replicating and nonreplicating), virus-like particles, protein subunit, RNA, DNA, nanoparticles, etc.[1],[2],[3],[4]


  Live Attenuated Vaccine/The Whole Virus Top


This is one of the most traditional techniques of vaccine preparation in which the viruses are cultivated under suboptimal conditions so that the virulence of the virus is decreased, but it holds the capacity of producing immunity in humans. The induction of immunity occurs mainly by mechanisms of Toll-like receptors, B-cells, CD4, and CD8 T-cells. It can be derived from “cold-adapted” virus strains, reassortants, and reverse genetics.[4] DelNS1- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- receptor-binding domain (RBD) (University of Hong Kong) is a type of live attenuated vaccine (LAV) based on influenza strain in which the NS1 gene has been omitted. It is grown in Madin-Darby canine kidney cells and/or in the chick embryo and is adapted to indicate the RBD of SARS-CoV-2 spike protein on its surface. It has more immunity potential than a wild influenza-type virus. It can be given as a nasal spray.[5]

This technique holds importance because the immunity generated by live attenuated viruses is pretty much as compared to other types of vaccines because the antibodies are generated not only against the spike proteins but also against various coronavirus antigens.[3]

However, the production of live attenuated virus vaccines is associated with biosafety risks because it becomes cumbersome to grow millions of viruses under suboptimal conditions. In addition, the handling and storage are also tough.[4] Although the researchers (Serum Institute of India) tried to produce LAVs, none of the vaccine projects completed the clinical trials. This may be because COVID-19 is a very spreadable virus which may not allow the mass production of live attenuated viruses.[3]


  Inactivated Virus Vaccine Top


These vaccines are based on the killed microorganisms and thus they are known as inactivated vaccine. Similar to LAV, this technique is also traditional. However, in comparison, it produces a shorter immunity in terms of duration. However, for coronavirus, its production is much more stable and the vaccine is better handled, is better stored, and is less expensive. Compared to mRNA vaccines, the immunity is produced against spike proteins and other coronavirus antigens. It can be used along with adjuvants to increase their immunogenicity. Limitations are that it requires the booster shots to maintain the immunity. It is interesting to note that China where the disease originated has approved CoronaVac and Sinopharm, both of which are inactivated vaccines. In our country, Bharat Biotech India manufactured Covaxin that has been popularly administered, which is a type of inactivated vaccine. However, most of the developing countries have still not approved Covaxin.[3],[4]


  Protein Subunit Vaccine Top


A subunit vaccine is based on recombinant antigenic proteins or synthetic peptides. It does not have any live component of the viral particle making it safe with fewer side effects.[4] These proteins are necessary for a solid and healthy, long-lasting therapeutic, and protective immune response.[6] The S-protein of the SARS-CoV-2 has been more potent in neutralizing antibodies. The S-protein has two subunits; the S1 subunit has the RBD, (NTD) N-terminal domain, and receptor binding motif (RBM) domains, whereas the S2 subunit consists of heptad repeat (HR) 1, and 2, and fusion peptide (FP).[7] The S-protein helps the virus bind to the hACE2 receptor, allowing the virus to enter the cell through endomitosis. This makes the S-protein, along with its antigenic fragments, the main target for the subunit vaccine institution.[6] The S-glycoprotein (a dynamic protein) has two states: prefusion and postfusion. Therefore, it is imperative for the antigen to keep its prefusion surface chemistry and profile so that epitopes can have a good quality antibody response.[8] Furthermore, targeting the masked RBM (as an antigen) will improve neutralization by antibodies, which will result in the vaccine's overall efficacy.[4] Novavax is one of the vaccines, which is made from protein subunit and has almost completed the clinical trials and may be launched in India soon.


  Viral Vectored Vaccines Top


Viral vector-based vaccines have an excellent prophylactic response against a pathogen. These vaccines show a highly specific gene delivery into the host cell with a vigorous immune response. Handling of any infectious particle is avoided, and it has been used widely for Middle East respiratory syndrome coronavirus with positive results from the trials.[4] These vaccines deliver the genes effectively to the target cells, produce an effective immune response, and are very efficient in gene transduction.[9] They provide an extended and high-profile appearance of antigenic proteins, which concludes its high prophylactic potential. These vaccines set off the cytotoxic T-cells, which eliminates the virus-infected cells.[10] Limitations are that the host may possess immunity against the vector due to prior exposure, reducing the efficacy.[4] Covishield and Johnson & Johnson are the vaccines which are based on adenovirus. The difference among them is that Covishield is based on chimpanzee adenovirus and Johnson & Johnson is based on human adenovirus, however, both of them differ significantly in terms of efficacy.


  mRNA Vaccine Top


mRNA is a noninfectious, upcoming, and nonintegrating platform. It poses no likely danger of insertional mutagenesis. The translation of mRNA occurs in the cytosol of the host cell averting the risk of any sort of integration into the host genome.[4] Vaccines' altercations can help improve the stability and can minimize the immunogenicity of the mRNA. Since mRNA is less immunogenic, it allows for specific immunity against the infection without causing much antivector immunity.[11] As it can copy the antigen structure and expression, this method has allowed rapid vaccine development.[12] Safety issues with reactogenicity have been reported for various RNA-based vaccines because of instability.[4] Most of the developed countries have relied on the mRNA vaccines, which is the most upcoming technology and is target based since only the mRNA fuses with the human genome, not allowing any other coronavirus antigen to spike immunity. This may have a shortfall in long run as any alteration in the basic genome of coronavirus may defy the immunity generated by specific mRNA vaccine.[3],[4],[5],[6],[7],[8],[9],[10],[11] Pfizer and Moderna are its candidate vaccines.


  DNA Vaccines Top


The development of the DNA vaccine has revolutionized vaccination, which encrypts for the antigen and a peripheral that produces the adaptive immune response. The transgene expressed by transfected cells provides a continuous supply of the transgene-specific proteins (similar to the live virus). Furthermore, the immature dendritic cells engulf the antigenic material, which dispenses the antigen to the CD8+ and CD4+ T-cells along with MHC 1 and MHC 2 antigens on the surface of the cell. It stimulates efficient humoral and cell-mediated immune responses.[13] The synthetic DNA is temperature stable and cold chain free. It can be developed at an accelerated pace. It does not require the handling of the infectious viral particle. Although it elicits both cytotoxic and humoral immunities, the titers remain low. Insertion of foreign DNA into the host genome may cause abnormalities in the cell. These vaccines may induce the antibody production against itself.[4]


  Others Top


Various biotech companies are trying on different technologies for vaccine development; British and American Tobacco Company introduced their new and vigorous tobacco plant technology.[5] Tianjin University has successfully made a vaccine which can be administered orally (uses Saccharomyces cerevisiae to carry the S-protein). Yeast has the generally regarded as safe status, which provides robustness, high scalability, and cost-effective production of a massive number of dosages required in this pandemic.[14] Furthermore, in silico studies (utilizing various databases such as VaxiJen) have shown epitope sequences YDPLQPEL and WTAGAAAYY can be used to formulate epitope-based peptide vaccines.[15]

The effectiveness and number of doses of vaccines are shown in [Table 1].
Table 1: Efficacy of various vaccines

Click here to view



  Side Effects of Vaccines Top


The mRNA vaccine has local (erythema, pain, lymphadenopathy, and swelling) and systemic side effects (fevers, myalgia, headaches, vomiting, and nausea).[16] The vaccine is given in two doses; the first dose prepares the immune system, whereas the second dose improves the immunity;[17] therefore, after the second dose, side effects were more. Twenty-one cases of anaphylaxis were noted out of the 1.8 million doses of Pfizer-BioNTech mRNA vaccines administered (no casualties).[16]

The phase 1/2 clinical trial of the ChAdOx1 nCoV-19 vaccine against COVID-19 had side effects such as pain, muscle aches, fever, chills, uneasiness, and headaches. The research team concluded paracetamol could be given for the same.[18] In a study conducted in Nepal, after the administration of Covishield to health-care workers, some health workers complained of mood irritability (after 4 h) and a few reported myalgia and nausea (after 6 h). Tenderness was reported at the site of injection, and they also felt feverish. Fever with chills developed (after 8 h), which got resolved by paracetamol.[19] Fever and headache resolved by the 2nd day. However, tenderness at the injection site and muscle pain persisted. Early morning awakening, tender injection site, and head heaviness continued on the 3rd day.


  Contraindications Top


Contraindications of the mRNA vaccine are severe or immediate allergic reaction (e.g., anaphylaxis) to a previous dose of mRNA COVID-19 vaccine or polysorbate or polyethylene glycol.[16] Persons with a history of anaphylactic or allergic reaction to a prior dose of COVID-19 vaccine, immediate or delayed-onset anaphylaxis or allergic reaction to vaccines or injectable therapies, pharmaceutical products, food items, etc., Before administering the vaccine to pregnant women, a lack of safety data should be discussed. People at the highest risk of severe infection should be preferred first until the validation of the safety and efficiency of this novel vaccine.[20]


  Vaccines for Mutant Strains Top


The resistant viruses survive for a longer duration, due to which they can replicate and spread their genetic material. These new variants spread faster, leading to concerns about vaccine efficacy.[21] Mismanage by authorities such as the slow rollout of vaccine, and rapid changes in the virus strain (mutated strain which is 50% more contagious), may sabotage antibody treatment diagnostic testing and vaccine efficacy. At present, the two variants of the COVID-19 vaccine, which are given to people in the US, have proven to be highly effective; as per the research, the immunity lasts for 8 months or more [Table 2].[21],[22]
Table 2: Summary of the effectiveness of some approved vaccines against new variants[23]

Click here to view



  Future Directions Top


It is evident that new vaccines have to be made, which will either replace or act as an adjunct to the current vaccine. Giving a cocktail of vaccines makes for an adequate remedy. It attacks several sites simultaneously, making it difficult for the coronavirus to escape the immune system. Another strategy can be developing vaccines with conserved protein that has a bleak chance of mutation to beat this budding issue.[23]

“Cobra Biologics and Karolinska Institutet in Sweden” are in the initial stages of manufacturing a unique DNA-based “super vaccine” pilot series. This vaccine will be genetically engineered. It will be given to the patient, which will produce an antigen leading to a response from the immune system, which would be safe, highly effective, and cost-efficient.[24]

Globally, several studies are in progress to associate the bacillus Calmette–Guérin (BCG) vaccination with COVID-19. Initial ecological studies demonstrated that countries where BCG vaccination was administered previously had fewer COVID-19 cases, and deaths per population were also less,[25],[26] suggesting that till the time a proper vaccine against COVID-19 is not developed, such trained immunity-inducing vaccines can be used to fill the gap.[27] Currently, with BCG, other LAVs are in use, such as modified vaccinia Ankara, measles, yellow fever virus, mumps, rotavirus, rubella, or attenuated influenza vaccines. Therefore, it will be intriguing to identify vaccines' effects that drive the natural immune response, with reservations about their level of protection, specificity, and durability.[28],[29]


  Conclusion Top


To control this pandemic, it is imperative to immunize the whole world. Technologies based on viral vector and mRNA have been the practical solutions. However, the ongoing mutations of the virus are troublesome, with newer research to focus on the effectiveness against the new strains.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  In this article
Abstract
Types of Vaccine...
Live Attenuated ...
Inactivated Viru...
Protein Subunit ...
Viral Vectored V...
mRNA Vaccine
DNA Vaccines
Others
Side Effects of ...
Contraindications
Vaccines for Mut...
Future Directions
Conclusion
References
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