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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 1  |  Page : 23-30

COVID vaccines: A step towards ending the pandemic


1 Department of Medicine, Sir Ganga Ram Hospital, New Delhi, India
2 Department of Family Medicine, Sir Ganga Ram Hospital, New Delhi, India
3 Department of Research Medicine, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission12-Jan-2021
Date of Decision17-Jan-2021
Date of Acceptance22-Jan-2021
Date of Web Publication19-Feb-2021

Correspondence Address:
Dr. Atul Kakar
Sir Ganga Ram Hospital, Old Rajinder Nagar, New Delhi - 110 060
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_6_21

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  Abstract 


COVID-19 pandemic has been associated with increased morbidity, mortality and economic loss globally. In the absence of definitive treatment, the only way to develop herd immunity and to curtail the spread of infection is through an effective vaccination programme. Under normal circumstances, a vaccine development would have taken 8–12 years; however, in case of COVID vaccine, this process has been reduced to 10 months. Since the lockdown, multiple countries have used various platforms to develop COVID vaccines at a war footing and recently close to five vaccines that have been approved for emergency use. This has lead to confusion, controversy and debate among the medical fraternity about the safety and efficacy of these vaccines. This articles gives an overview of the vaccines present, various trial results and adverse effects seen till now.

Keywords: Adverse effects, covaxin, COVID vaccine, covishield


How to cite this article:
Kakar A, Gogia A, Sipani S, Gulati S, Batra T, Jain K, Jain S, Tripathi S. COVID vaccines: A step towards ending the pandemic. Curr Med Res Pract 2021;11:23-30

How to cite this URL:
Kakar A, Gogia A, Sipani S, Gulati S, Batra T, Jain K, Jain S, Tripathi S. COVID vaccines: A step towards ending the pandemic. Curr Med Res Pract [serial online] 2021 [cited 2021 Mar 1];11:23-30. Available from: http://www.cmrp.org/text.asp?2021/11/1/23/309919




  Introduction Top


The development of a vaccine against a particular pathogen is a time-consuming and tedious process. Usually, time taken from bench to bed side for any new drug or vaccine which is introduced in 10–12 years and includes vigorous trials for the study of safety and efficacy.[1] In the present scenario, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seems to be the only hope to control the pandemic and was available in about 10 months for public health use. All the scientific community and the people who have worked for the development of the vaccine need to be applauded.

Over the past decade, vaccines have appreciably augmented life expectancy of humans. Many diseases such as small pox and polio have been eradicated with the help of vaccines. Several other diseases such as tetanus, hepatitis B, pertussis and diphtheria have seen a lesser burden in community, thanks to universal vaccination programme. The research and development of COVID-19 vaccine was well supported financially and politically world over.[2] With the fast track approvals of the vaccine, there have been controversies about the type of vaccine and its effectiveness. This article attempts to provide scientific data on the vaccine and clarify myths around the COVID vaccine.


  Immunity and Vaccination Top


Understanding the types of immunity is important to understand about vaccination. As soon as the virus enters the lung, the host immune response is activated. On the daily basis, the human body is challenged with multiple respiratory pathogens which the body tries to eliminate through cough reflex. The coronavirus escapes this reflex and enters the respiratory tissues hence damaging it. The innate immunity plays the first line of defence in the virus clearing, which is brought about by macrophages. This initiates the adaptive immunity through cytokines and chemokines secretions which involves T-cell and B-cell response. The CD4 T-cells are responsible for an antibody response which the CD8 T-cells kill the virus infected cells directly [Figure 1].[3] SARS-CoV-2 infection and the destruction of lung cells triggers a local immune response, recruiting macrophages and monocytes that respond to the infection, release cytokines and prime adaptive T- and B-cell immune responses. In most cases, this process is capable of resolving the infection. However, in some cases, a dysfunctional immune response occurs, which can cause severe lung and even systemic pathology.
Figure 1: How Moderna vaccine works (Adapted from: https://www.modernatx. com/moderna-blog/shedding-light-our-prophylactic-vaccines-moa)

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The gene sequence of SARS-CoV-2 was made available from laboratories soon after it was identified as a betacoronavirus, and subsequently, the scientific community started working on the possible targets for the vaccine. Studies based on non-human primate challenge models suggest that the neutralising antibodies against SARS-CoV-2 prevent viral entry and also protect against SARS-CoV-2. Passive transfer of convalescent plasma from recovered COVID-19 patients decreased viral burden in recipient SARS patients and is being frequently used as a potential treatment for COVID-19.[4],[5] These findings have led to the use of neutralisation assays to assess immune responses in recent human COVID-19 vaccine trials.[6]

Herd immunity, on the other hand, refers to an indirect form of protection which occurs when a larger population has become immune to a certain infection, reducing the risk of infection in the individuals who lack immunity. Herd immunity is the target point of any vaccination programme. Figure 1 depicts the role of B- and T-cells in COVID infection.


  Types of Vaccines Top


At present, 166 vaccines in pre-clinical phase and 56 vaccines in clinical trials (phase 1–3) and some have also received emergency authorisation for their use.[7] Nine different technology platforms for COVID-19 vaccine are under research and development, these include the protein subunit, virus like particle, inactivated virus, live attenuated virus, DNA based, mRNA based, chimpanzee adenovirus non-replicating viral vector, human serotype 26 non-replicating viral vector and human serotype 5 adenovirus non-replicating viral vector [Table 1].[6] [Table 2] and [Table 3] highlight the key differences in few of the major vaccines which are being made available for administration. The safety and efficacy of these vaccines and their adverse effect profile remain a constant topic of debate due to the fear of fast-tracking the clinical trials for these vaccines. The effectiveness of any vaccine depends on its efficacy[6] which is denoted by the percentage of reduction of an infection in a vaccinated group of people compared to an unvaccinated group. [Table 4] enlists some of the commonly noticed local and systemic side effects of covid vaccine during trails. The WHO has set a minimal efficacy limit of 50% for the vaccine approval, while an efficacy of <60% might fail to achieve herd immunity.[6] It is difficult to tell how long immunity produced by vaccination will last, until there are more data on how well the vaccines work.
Table 1: Types of COVID vaccine

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Table 2: Comparative sheet for different COVID-19 vaccines, under India Government supply

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Table 3: Differences seen are between moderna and pfizer COVID vaccine

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Table 4: Common adverse effects seen with COVID-19 vaccines

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  Indications of Vaccine Top


As of January 11, 2021, at the time of writing this article, more than 2.4 million injections or doses of COVID vaccines have already been administered to various people in the world. Currently, in the first phase of vaccine administration in India, it has been recommended for health-care workers and front-line workers. In the subsequent phase, people above the age of 50 years and people below 50 years with risk factor would receive the vaccine.

The World Health Organisation has mentioned that the vaccine should be for all and equally distributable.[7] The recommendations which were made by Centres for Disease Control and Prevention with these goals in mind are:[8]

  • Decrease the morbidity and mortality due to COVID-19
  • Restore functioning of our society
  • Decrease the additional burden from COVID-19 which is leading to disparities in society.


Restricted or emergency use authorisation (EUA) of the vaccine is given during a pandemic situation based on animal studies, safety data of phase 1 and 2 trials and the available phase 3 data. In addition, it is expected that an ‘EUA request includes a phase 3 safety database of well over 3000 vaccine recipients, representing a high proportion of participants enrolled in the phase 3 study, who have been followed for serious adverse events and adverse events of special interest for at least 1 month after completion of the full vaccination regimen.'[9] Drug Controller General of India (DCGI) approved India's first indigenous vaccine against COVID-19 for restricted use. This means it should not be given to everyone. Only those in extreme need of it based on his/her medical condition will be given the vaccine.[10]


  Covishield Top


Covishield vaccine (ChAdOx1 nCoV-19), labelled as AZD1222, is a viral vector vaccine developed at Oxford University/AstraZeneca with Serum Institute of India (SII) providing a platform for producing a vaccine in India. Covishield consists of a replication-deficient chimpanzee adenoviral vector (ChAdOx1) comprising of SARS-CoV-2 structural surface glycoprotein antigen (spike-protein). This was the first COVID vaccine approved in the world.

Trials for this vaccine were carried out in the United Kingdom (UK), Brazil, South Africa and India. In a recent article titled ‘Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial’ provided single-blind, randomised trial carried out at five sites in the UK in individuals between the age group of 18–55 years. The voluntary healthy individuals were assigned in 1:1 ratio (with 543 participants in each group). The dose of vaccine used was 0.5 ml. Two out of the five sites (Oxford and South Hampton) allowed prophylactic use of 1 g of intravenous paracetamol 6 hourly for 24 h.[5] Humoral and cellular responses of the patients were assessed. The primary end point was decided on the basis of:

  1. a. Efficacy – measured by cases of symptomatic, virologically confirmed Covid-19 cases
  2. Safety – Occurrence of severe adverse effects.


In the patients who received AZD1222 vaccine, local and systemic reactions were more common (in terms of fever, chills, myalgias, headache and malaise) (P < 0.05). However, there was no evidence of any serious adverse events. Severity of the side effects was graded as mild, moderate, severe and potentially life-threatening.[11]

Several adverse effects were seen such as fatigue, tenderness at site of injection, muscle aches, malaise, chills, feeling feverish and objective fever. All these adverse effects were seen more in Covishield recipients not taking paracetamol, except for fatigue.

In the same patients, it was noted that T-cell response peaked on day 14, antispike IgG response peaked on day 28. A booster dose was given on day 28 after which neutralising activity was measured in all patients. Neutralising antibody response correlated strongly with antibody levels measured by the enzyme-linked immunosorbent assay (P < 0.001).

Other than these two randomised groups, 10 patients were non-randomised (labelled as group 3), called as Prime Boost group, who received 0.5 ml AZD1222 on day 1 and day 28.

In the boost group, side effects were measured for 7 days and appeared to be less severe.

The drawbacks of this study were as follows:

  • Less number of participants
  • Most of the participants belonged to white race
  • Long-term side effects unknown.


In another study done, an interim analysis of the randomised controlled trials in Brazil, South Africa, and the UK comprising of data from four different trials, the ChAdOx1 nCoV-19 vaccine and control groups were assigned 1:1 participant. 5 × 1010 viral particles were used in vaccine (two doses). Only in the UK site, first dose was given half the original assigned dose and the second dose was as per the standard protocol. Data were divided as:

  • COV 001 – Phase 1/2 (UK)
  • COV 002 – Phase 2/3 (UK)
  • COV 003 – Phase 3 (Brazil)
  • COV 005 – Phase 1/2 (UK).


The primary objective was the efficacy of vaccine against nucleic acid amplification test confirmed COVID-19. The study showed 70.4% efficacy after two doses and 64.1% efficacy after at least one standard dose.[11]

First dose of the Covishield vaccine was administered at BVP medical college, Pune, during the phase 3 trials. Subsequently, 1600 participants were chosen (above the age of 18 years) at 17 different sites in India. The results of safety and efficacy were similar to as seen in the international trial. This led to the approval of restricted emergency use of this vaccine in India by DCGI.[5] The Government of India will procure the vaccine from the SII, Pune and will administer to health-care workers. The vaccine needs to be stored at 2°C–8°C which can be easily done across India in refrigerators.


  Covaxin Top


Covaxin (BBV152) is a whole virion inactivated SARS-CoV-2 vaccine and is the first vaccine which has been indigenously prepared. It has been developed by Bharat Biotech in collaboration with the Indian Council of Medical Research. The virus strain (National Institute of Virology [NIV]-2020-770) isolated from a COVID-19 patient and sequenced at the Indian Council of Medical Research-NIV was provided to Bharat Biotech which has a well-established Vero cell manufacturing platform aided in rapid development of BBV-152 vaccine, formulated with a TLR 7/8 agonist molecule absorbed to alhydroxiquim-II (algel-IMDG).[12]

The vaccine needs to be injected through the intramuscular route at a volume of 0.5 ml/dose in a two-dose regimen. BBV152 vaccine requires to be stored between 2°C and 8°C, which is very much compatible with developing countries like India.[13]

Pre-clinical trials in mice, rats, and rabbits and live viral challenge protective efficacy studies in hamsters and non-human primates helped in the development of BBV152. Two-dose vaccination regimen of inactivated vaccine candidates was administered in 20 rhesus macaques. The results showed protective efficacy, increasing SARS-CoV-2-specific IgG and neutralising antibodies, reducing replication of the virus in the nasal cavity, throat and lung tissues of monkey. Adverse events were not seen in animals immunised with a two-dose vaccination regimen.[14],[15],[16],[17]

The vaccine was well tolerated in all groups and there was not any vaccine-related serious adverse event reported in phase 1 clinical trials.[17] Most common side effect that was noticed was pain (incidence rate 10%–20%) which resolved spontaneously and was noticeably lower than other vaccines. Furthermore, no premedication was given to the participants in phase 1 trials.[12],[13],[14]

The vaccine was prepared in three dose form (3 mcg-algel-IMDG, 6 mcg-algel-IMDG, 6 mcg-algel) for phase 1 clinical trials. BBV152 whole virion inactivated vaccine with algel-IMDG preparation produces strong humoral and cell-mediated response similar to other inactivated vaccines for SARS-Cov-2 and it is the first vaccine that induce a Th1-biased response as reported in phase 1 clinical trials.[18]

BBV152 induced T-cell memory response as demonstrated in phase 2 trials. Hence, it can be hypothesised that after the second dose, the humoral and cell-mediated response may persist until at least 12 months.[18] None of the other SARS-CoV-2 inactivated vaccines reported such immunogenic response.[12],[13],[14] In phase 2 trials, 3 mcg-algel-IMDG and 6 mcg-algel-IMDG preparations were selected. Both the preparations showed neutralising antibodies in all participants on day 104 after the second dose. Hence, BBV152 has potential to provide durable humoral and cell-mediated immunity.

Whole virion inactivated virus technique has been used in many other vaccines such as influenza, polio and rabies and is a time tested platform for vaccination. Currently, 6 mcg with algel-IMDG formulation of BBV152 received DCGI approval for Phase 3 clinical trials in 25,800 participants in over 25 centres across India.[19]


  Moderna Vaccine Top


The mRNA-1273(Moderna) vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilised full-length spike protein of the SARS-CoV-2. This is for the first time that m-RNA platform has been used and there have been many speculations regarding this vaccine.

In Phase I, dose escalation clinical trial of mRNA-1273 showed dose-dependent induction of neutralising antibodies against S1/S2 as early as 15 days post-injection. As of November 2020, the Moderna COVID-19 vaccine candidate, mRNA-1273, had shown preliminary evidence of 94% efficacy in preventing COVID-19 disease in a Phase III trial, with only minor flu-like side effects. This led to its submission for EUA in Europe, the United States and Canada

In phase 3 randomised, observer-blinded, placebo-controlled trial, enrolling 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo, the most common injection site event was pain after injection (86.0%). Injection site events were mainly graded 1 or 2 in severity and lasted a mean of 2.6 and 3.2 days after the first and second dose, respectively. Delayed injection site reactions (those with onset on or after day 8) were noted in 244 participants (0.8%) after the first dose and in 68 participants (0.2%) after the second dose. Reactions were characterised by erythema, induration and tenderness, and they resolved over the following 4–5 days. Solicited systemic adverse events occurred more often in the mRNA-1273 group than in the placebo group. Both solicited injection site and systemic adverse events were more common among younger participants (18 to <65 years of age) than among older participants (≥65 years of age). Treatment-related severe adverse events were higher in the mRNA-1273 group. Key limitations of the data are the short duration of safety and efficacy follow-up. Although our trial showed that mRNA-1273 reduces the incidence of symptomatic SARS-CoV-2 infection, the data are not sufficient to assess asymptomatic infection.[20]


  Pfizer Vaccine Top


BNT162b2, a lipid-soluble nano particle-based mRNA vaccine, has been developed by Pfizer and BioNTech. The preparation consists of perfusion conformation of the full-length S gene.[21] In theory, BNT162b2 should be highly immunogenic taking into account the molecular structure of COVID-19 and its interactions as explained by past studies.[22] However, the results of a comparative study between BNT162b1 and BNT162b2 showed that both of them, dose-dependently, induced similar serum neutralising antibody titres, which were significantly higher than those in convalescent sera. However, BNT162b2 generated milder adverse reactions than BNT162b1 and it also showed higher efficacy in the elderly individuals.[23],[24] In a promising study, strong Th1-type CD4 + and interferon gamma (IFN-γ)+ CD8 + T-cell responses were produced in both mice and rhesus monkeys during the animal trial and were able to completely protect the lungs of rhesus monkeys from SARS-CoV-2 infection.[25]

Pfizer had said its Covid vaccine has attained 90% efficacy. Two days later, Russia's Gamaleya Institute said its vaccine Sputnik V was one step better-92 percent. Moderna, which is also developing its vaccine on mRNA technology, said its vaccine had shown 94.5 percent efficacy. Then came another claim by Pfizer, which said the final analysis of its vaccine candidate suggests it is 95 percent effective against coronavirus


  BBIBP-CORV (Beijing Institute of Biological Products) Top


The Beijing Institute of Biological Products produced the inactivated BBIBP-CorV vaccine. Inactivated with β-propyl lactone, this vaccine, induced high titres of neutralising antibodies in mice and rhesus monkeys, published in studies involving animal trials.[26] A promising aspect that was unveiled during the studies for this vaccine was that there was no adverse drug effect in the pulmonary tissue of immunised monkeys. In its phase I trials, close to one-third of the vaccine group experienced at least one adverse reaction 7 days after inoculation, but these were primarily mild-to-moderate, and no serious adverse reactions occurred within 4 weeks of inoculation.[27] Positive serum antibodies were found in the majority of vaccine group post-inoculation. As a conclusion, the results showed that the BBIBP-CorV vaccine is safe and well tolerated in all groups, and that neutralising antibodies were produced in all participants after prime inoculation.


  Coronavac (Sinovac Life Sciences) Top


A multivalent inactivated vaccine that targets SARS-CoV-2 strains circulating in several regions, CoronaVac, was developed by SinoVac Life Sciences, Beijing, China.[28] β-propyl lactone was utilised to inactivate the viral seed which was cultured in Vero cells. According to the result of the animal trials in mice and rats, the neutralisation titer in the serum of the vaccination group was significantly higher than that in the convalescent serum of COVID-19 patients. A promising addition to all of this was the exhibition of a broad-spectrum immune response by the immune serum, which was further able to neutralise 10 different strains of SARS-CoV-2. Neither any pulmonary complication nor any other adverse drug effect was observed after virus challenge in rhesus monkeys, pointing towards the safety and high-level protection offered by the vaccine.[29] The vaccine was well tolerated, and there were no safety risks associated with vaccination. The adverse reactions were relatively mild, and no adverse reactions above grade 3 occurred.

{Table 1}Sputnik-V (Gamaleya Research Institute Vaccine, Russia)[/TAG:2]

The Gamaleya Research Institute, Russia developed its human adenovirus (Ad) vector based vaccine, the Sputnik-V, which has a full length S-gene.[30] The peculiar feature of this vaccine is that it utilises 2 Ad vectors-Ad5 and Ad26.[31] During the clinical trials, the most common, although only mild-to-moderate, adverse drug effects that were found were pain at the site of injection and hypothermia.[32] Further, as per previous knowledge of the non-structural proteins and the open reading frames in the genome of the virus[22] and the standing immunity in the human population towards adenoviruses, it was well expected that usage of recombinant adenovirus vectors could have posed a problem, yet the results during the trials of Sputnik-V were promising with optimal proliferation of CD4 + and CD8 + T-cells, along with the secretion of IFN-?, both of with pointed towards an effective T-cell response.[32] Sputnik-V has a decent efficacy and utilises the nanotechnology which can prove to be really effective for the process of tackling the virulence.[31],[33],[34]


  Zydus Cadila Vaccine Top


ZYCoV-D is another indigenously developed plasmid DNA third-generation vaccine where DNA, the active part of virus is injected into the plasmid that is non-replicating and non-integrating. This recombinant plasmid is then available in vaccine form which generates antigen-antibody response and cell mediated immunity.

The vaccine is injected intradermally on days 0, 28 and 56 in a dose of 0.1 ml in either of the arms. The vaccine is available in 10 dose vial formulation and is very stable at 2°C-8°C. It can be stored at normal refrigerator temperature. The vaccine is also thermostable (not readily deactivated by heat) at 25° Celsius. The vaccine has biosafety requirement of BSL level1.

Clinical trials included the age group of 18–55 years. Phase I trial began on 15th July 2020 and was monitored for 7 days for safety endorsed by the Data and Safety Monitoring Board. Phase II trial began on 6th August 2020 with 1000 healthy adult volunteers’ adaptive phase I/II dose escalation as multicentric double-blind placebo randomised control trial (RCT) across 11 cities.

Phase III trial a double-blind placebo RCT is planned to start mid-January at over 60 clinical trial sites with 30,000 participants with results for efficacy expected in early April. The first primary objective analysis will be based on 158 cases of COVID-19. Outcomes seem promising with this indigenously made only DNA plasmid vaccine with geometric mean titres of 20–80 folds rise in antibody levels.


  Adverse Events Following Immunisation of COVID-19 Top


Any adverse reaction occurring post immunisation, which does not necessarily have a direct relationship with the usage of the vaccine and adverse event may be any minor to severe, abnormal laboratory findings, symptoms, signs or disease will be included.


  Unsolicited Adverse Events of Pfizer-Biontech Vaccine Top


  1. Lymphadenopathy occurred in the arm and neck region and was reported within 2–4 days after vaccination. The average duration of lymphadenopathy was approximately 10 days
  2. Bell's palsy was reported by four vaccine recipients and none of the placebo recipients. The Bell's palsy was self-limiting in all cases.


For the prevention of adverse events following immunisation of COVID-19 symptoms and signs are observed for at least 30 min postvaccinations to detect, manage and treat immediate adverse reactions. Vaccination is conducted at the health facilities (both government and private) where medical officer/doctor is available at the fixed session site. At these sites, an AEFI management kit or an emergency tray should be available for the use. The contents of the AEFI kit are as follows: Injection adrenaline (1:1000) (3), Injection hydrocortisone (3), ringer lactate/normal saline (2), 5% dextrose (2), IV drip set (2), scalp vein sets or IV cannula (2), disposable syringes (3 sets), adhesive tape and blank case reporting formats is available to manage these adverse events and outreach session sites have an Anaphylaxis kit.


  National Programme for COVID-19 Vaccination Top


  • The Ministry of Health and Family Welfare, Government of India will role out the vaccines
  • Training program for vaccination of 3 million people in India in phase 1 has been conducted across the country
  • Registration and implementation will be through COVID Vaccine Intelligence Network (Co-WIN) system; a digital computer-based system
  • Only preregistered beneficiaries will be vaccinated
  • The National Expert Group on Vaccine Administration for COVID-19 have laid the recommendations for the vaccination programme in India.



  Conclusions Top


Vaccination for the prevention of infectious agents has been done for over 100 years. Due to the severe health risks associated with COVID-19 and the fact that re-infection with COVID-19 is possible, vaccine should be taken by all regardless of whether you have already suffered COVID-19 infection.

Vaccination against COVID-19 has been developed in fast-track mode. In Phase 2/3 of the clinical trials have examined their safety and efficacy, and these data have been analysed at length by various drug regulatory authorities. Although we do not have long-term effects of vaccination, still we should encourage everyone to come forward to take the vaccine and thus build herd immunity against this disease. As protection these vaccines gives outweighs the long-term risks that may or may not be present. People who have underlying condition such as diabetes and heart disease are at a high risk for getting complications from COVID-19, so it's even more a reason why they should get vaccinated.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol 2011;162:1239-49.  Back to cited text no. 1
    
2.
Yadav S, Rawal G. The coronavirus disease 2019 vaccine – A step to halt the devastation by the pandemic of SARS-CoV-2. IP Indian J Immunol Respir Med 2020;5:196-7.  Back to cited text no. 2
    
3.
Wang YT, Landeras-Bueno S, Hsieh LE, Terada Y, Kim K, Ley K, et al. Spiking pandemic potential: Structural and immunological aspects of SARS-CoV-2. Trends Microbiol 2020;28:605-18.  Back to cited text no. 3
    
4.
Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2020;396:479-88.  Back to cited text no. 4
    
5.
Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020;396:467-78.  Back to cited text no. 5
    
6.
Nikhra V. Stages in COVID-19 vaccine development: The nemesis, the hubris, and the elpis. Int J Clin Virol 2020;4:126-35.  Back to cited text no. 6
    
7.
8.
Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect.html.COVID vaccine. [Last accessed on 2021 Jan 10].  Back to cited text no. 8
    
9.
Emergency Use Authorization | FDA. Avaialle from: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization. [Last accessed on 2021 Jan 09].  Back to cited text no. 9
    
10.
What Does Emergency Use Mean as India Gets Two Vaccines Against COVID-19?. Available from: https://www.india.com/lifestyle/what-does-emergency-use-mean-as-india-gets-two-vaccines-against-covid-19-4305672/. [Last accessed on 2021 Jan 09].  Back to cited text no. 10
    
11.
Voysey M, Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of the randomised controlled trials in Brazil, South Africa and the UK. Lancet 2021;397:99-111.  Back to cited text no. 11
    
12.
Serum Institute Registers Its Covid-19 Vaccine Trial, 21 August, 2020. Available from: https://www.hindustantimes.com. [Last accessed on 2021 Jan 09].  Back to cited text no. 12
    
13.
Available from: https://www.bharatbiotech.com/covaxin.html. [Last accessed on 2021 Jan 09].  Back to cited text no. 13
    
14.
Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, et al. A Phase 1: Safety and immunogenicity trial of an inactivated SARS CoV 2 vaccine BBV152. medRxiv 2020 Dec;20210419. [doi: http://doi.org/10.1101/2020.12.11.20210419].  Back to cited text no. 14
    
15.
Ganneru B, Jogdand H, Dharam VK, Molugu NR, Prasad SD, Vellimudu S, et al. Evaluation of safety and immunogenicity of an adjuvanted, TH 1 skewed, whole virion inactivated SARS CoV 2 vaccine BV152. bioRxiv 2020 Sept; 285445. [doi: https://doi.org/10.1101/2020.09.09.285445].  Back to cited text no. 15
    
16.
Mohandas S, Yadav PD, Shete A, Abraham P, Mohan K, Sapkal G, et al. Immunogenicity and protective efficacy of BBV152: A whole virion inactivated SARS CoV 2 vaccine in the Syrian hamster model. iScience 2021 Jan; 102054. [https://doi.org/10.1016/j.isci.2021.102054]  Back to cited text no. 16
    
17.
Yadav P, Ella R, Kumar S, Patil K, Mohandas S, Shete A, et al. Remarkable immunogenicity and protective efficacy of BBV152, an inactivated SARS CoV 2 vaccine in rhesus macaques. Research Square 2020 Sept; doi: 10.21203/rs.3.rs-65715/v1.  Back to cited text no. 17
    
18.
Zhang YJ, Zeng G, Pan HX, Li CG, Kan B, Hu YL, et al. Immunogenicity and safety of a SARS CoV 2 inactivated vaccine in healthy adults aged 18 59 years: Report of the randomized, double blind, and placebo controlled phase 2 clinical trial. medRxiv 2020 Aug; 20161216. [doi: https://doi.org/10.1101/2020.07.31.20161216].  Back to cited text no. 18
    
19.
Sanders B, Koldijk M, Schuitemaker H. Inactivated viral vaccines. Vaccine Analysis: Strategies, Principles, and Control. 2015; 45 80. https://doi.org/10.1007/978-3-662-45024-6_2 [Last accessed on 2021 Jan 11].  Back to cited text no. 19
    
20.
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and Safety of the mRNA 1273 SARS CoV 2 vaccine. N Engl J Med 2021;384:403-16. Availale from: https://doi.org/101056/ NEJMoa2035389. [Last accessed on 2021 Jan 08].  Back to cited text no. 20
    
21.
Li DD, Li QH. SARS-CoV-2: Vaccines in the pandemic era. Mil Med Res 2021;8:1.  Back to cited text no. 21
    
22.
Tripathi S, Gogia A, Kakar A. COVID-19 in pregnancy: A review. J Family Med Prim Care 2020;9:4536-40.  Back to cited text no. 22
  [Full text]  
23.
Walsh EE, Frenck R, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. RNA based COVID 19 vaccine BNT162b2 selected for a pivotal efficacy study. N Engl J Med 2020; 383:2439-2450. DOI: 10.1056/NEJMoa2027906.  Back to cited text no. 23
    
24.
Walsh EE, Frenck RW Jr., Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates. N Engl J Med 2020;383:2439-50.  Back to cited text no. 24
    
25.
Vogel AB, Kanevsky I, Che Y, Swanson KA, Muik A, Vormehr M, et al. A prefusion SARS CoV 2 spike RNA vaccine is highly immunogenic and prevents lung infection in non human primates. bioRxiv 2020 Sept 08; 280818. [doi: 10.1101/2020.09.08.280818].  Back to cited text no. 25
    
26.
Wang H, Zhang Y, Huang B, Deng W, Quan Y, Wang W, et al. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell 2020;182:713-21.  Back to cited text no. 26
    
27.
Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: A randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis 2021;21:39-51.  Back to cited text no. 27
    
28.
Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, et al. Rapid development of an inactivated vaccine for SARS-CoV-2. bioRxiv 2020;369:77-81.  Back to cited text no. 28
    
29.
Zhang YJ, Zeng G, Pan HX, Li CG, Kan B, Hu YL, et al. Immunogenicity and safety of a SARS CoV 2 inactivated vaccine in healthy adults aged 18–59 years: Report of the randomized, double blind, and placebo controlled phase 2 clinical trial. medRxiv 2020 August 31; 20161216. [doi:http://doi.org/10.1101/2020.07.31.20161216].  Back to cited text no. 29
    
30.
Availale from: https://sputnikvaccine.com/about vaccine/. [Last access on 2021 Jan 08].  Back to cited text no. 30
    
31.
Chung YH, Beiss V, Fiering SN, Steinmetz NF. COVID-19 vaccine frontrunners and their nanotechnology design. ACS Nano 2020;14:12522-37.  Back to cited text no. 31
    
32.
Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: Two open, non-randomised phase 1/2 studies from Russia. Lancet 2020;396:887-97.  Back to cited text no. 32
    
33.
Cohen J. with Record-Setting Speed, Vaccinemakers Take Their First Shots at the New Coronavirus. Available from: https://www.sciencemag.org/news/2020/03/record-setting-speed-vaccine-makers-take-their-first-shots-new-coronavirus. [Last accessed on 2020-Aug 14].  Back to cited text no. 33
    
34.
Lowe D. The Russian Vaccine. Available from: https://blogs.sciencemag.org/pipeline/archives/2020/08/11/the-russian-vaccine. [Last accessed on 2020 Aug 14].  Back to cited text no. 34
    


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Abstract
Introduction
Immunity and Vac...
Types of Vaccines
Indications of V...
Covishield
Covaxin
Moderna Vaccine
Pfizer Vaccine
BBIBP-CORV (Beij...
Coronavac (Sinov...
Zydus Cadila Vaccine
Adverse Events F...
Unsolicited Adve...
National Program...
Conclusions
References
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