|Year : 2021 | Volume
| Issue : 1 | Page : 24-29
An update on coronavirus disease-19 vaccines
Madhu Gupta, Isha Kapoor
Department of Community Medicine, School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Submission||31-Jan-2021|
|Date of Acceptance||01-Mar-2021|
|Date of Web Publication||25-Apr-2021|
Dr. Madhu Gupta
Department of Community Medicine, School of Public Health, Postgraduate Institute of Medial Education and Research, Sector 12, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
Coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in massive health and economic burden. There has been substantial morbidities and mortalities owing to its high transmission rate. Therefore, effective strategies for treatment and prevention are crucial. Vaccines offer a ray of hope for the prevention and controlling the spread. Various new technological platforms have been utilised for vaccine production. The current review provides a brief description of these platforms for vaccine production and an update on the available and upcoming COVID-19 vaccines, discussing their results and outcomes from different trial phases. We have also focused on COVID-19 vaccination drive in India, emergency use authorisation, other candidate vaccines in Indian landscape, and issues involved with their clinical use and current recommendations.
Keywords: Vaccine, SARS CoV2, COVID-19, Coronavirus
|How to cite this article:|
Gupta M, Kapoor I. An update on coronavirus disease-19 vaccines. J Med Evid 2021;2:24-9
The ongoing pandemic of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a major health and economic disruption. As of January 27, 2021, over 99.8 million people globally have been diagnosed with COVID-19, resulting in more than 2.1 million deaths. With 10.6 million reported cases and over 153700 deaths, India has registered the second highest number of confirmed cases and the third highest death toll among all countries. SARS-CoV-2 is the third coronavirus, after SARS CoV and Middle East respiratory syndrome coronavirus, to emerge in the human population in the past two decades, leading to a global public health emergency. On December 31, 2019, a novel coronavirus was identified in a cluster of cases of pneumonia reported at Wuhan from where it had swiftly spread across the globe, and on March 11, 2020, the World Health Organization (WHO) characterised COVID-19 outbreak as a pandemic.
| Introduction|| |
To understand how COVID-19 vaccines might work to prevent the COVID-19 infection, it is important to learn about the morphology of coronavirus. Coronaviruses are positive-sense single-stranded viruses with RNA as genetic material. SARS-CoV-2 has a spherical shape with four types of structural proteins including spike protein, envelope protein, membrane glycoprotein and nucleocapsid protein. After invasion, it activates the host's immune system by initially inducing innate immune response, characterised by the production of cytokines, antiviral interferons and different chemokines and then subsequently generating adaptive immunity wherein T cells activate B lymphocytes to produce neutralising antibodies. Neutralising antibodies to spike protein have been hypothesised to prevent entry of virus via angiotensin-converting enzyme 2 (ACE 2) receptor, thereby inhibiting infection.
| Approaches to Vaccine Development|| |
Safe and effective vaccines would be instrumental in containing the rapid transmission, thereby reducing disease burden and mortality. The categories of vaccines undergoing trials are:
| Vaccine Production Platforms|| |
- Viral vector vaccines: The gene for pathogen protein is inserted into another virus (e.g., adenovirus) that can produce proteins without causing disease; thus, the safe virus serves as a 'platform' or 'vector' to deliver the protein for triggering an immune response. An advantage of this platform is the capability to induce both humoral and cellular immunity. The recombinant viral vectors can be replicating or non-replicating, depending on their ability to multiply in the host cell. Oxford vaccine, Covishield and Sputnik V are examples of viral vector vaccines
- Whole cell viral vaccines: The virus is selected, modified (weakened) or completely inactivated, so that it is no longer able to induce infection, but able to induce immune response and therefore mimic features of natural infection. Both humoral and cellular immune responses are induced. Inactivated SARS-CoV-2 vaccine (Vero cell) and BBV152 (Covaxin) use this platform
- Nucleic acid vaccines (RNA and DNA): Instead of a virus, nucleic acid is inserted which results in the production of virus protein copies. Vaccines developed by Pfizer/BioNTech, Moderna and Zydus Cadila are based on this new technology
- Protein-based vaccines: Protein subunits (extracted from the virus and purified) and virus-like particles are injected. These protein multimers mimic the structure of real virus and stimulate antigen-presenting cell-mediated activation of B-and T-cell immune responses. Examples include Novavax and AdaptVac.
Remarkable efforts have been directed towards the accelerated development of the vaccines against COVID-19 by scientists worldwide. The WHO is collaborating with scientists, business and global health organisations through the Access to COVID-19 Tools Accelerator and COVAX (led by WHO, GAVI and CEPI) to facilitate equitable access and distribution of COVID-19 vaccines. There are currently 237 candidate vaccines in the draft COVID-19 vaccine landscape, from which 64 candidate vaccines are in clinical evaluation while 173 are undergoing preclinical development.
The steps in routine vaccine development include pre-clinical phase where vaccine is tested in animal studies for efficacy and safety, then clinical trials where in Phase 1, small groups of healthy adult volunteers receiving vaccine are tested for safety, in Phase 2 safety and immunogenicity is assessed, Phase 3 is done on thousands of people to test efficacy and safety, while Phase 4 post marketing surveillance is carried out after vaccine is approved and licensed, to monitor adverse events and to study long term effects of the vaccine. Usually, these steps are performed in sequence; however, to accelerate COVID-19 vaccine development, these steps are done in parallel, but all the monitoring mechanisms such as adverse event surveillance, safety data monitoring and long-term follow-up remain in place. To achieve rapid progress towards the global objectives, the WHO solidarity trial aims to evaluate different candidate vaccines, enrol expeditiously in areas of high COVID-19, along with international collaboration and country commitment for ensuring equitable access to vaccines.
| Coronavirus Disease-19 Candidate Vaccine Landscape|| |
Viral vector vaccines
ChAdOx1 nCoV-19 vaccine
Developed by University of Oxford and AstraZeneca, ChAdOx1 nCoV-19 vaccine (AZD1222) consists of non-replicating simian adenovirus vector ChAdOx1 containing full-length structural spike protein of SARS-CoV-2. The preliminary report of Phase I/II, single-blind, randomised controlled trial in five trial sites in the United Kingdom (UK) showed that this vaccine has an acceptable safety profile with no serious adverse reaction, and that two doses sufficiently induced cellular and humoral immunogenicity in the participants. On further phase ⅔ results, this vaccine was found to be safe and well tolerated, and antibody responses against SARS-CoV-2 spike protein were induced, boosted and maintained at 28 days after second vaccination, and cellular immune responses were also induced peaking at day 14 after vaccination, in all age groups. Overall vaccine efficacy across four randomised trials in Brazil, South Africa and UK was 62%. Based on this technology, Serum Institute of India (SII) is manufacturing Covishield vaccine. A Phase 2/3 trial on 1600 healthy Indian volunteers is ongoing for Covishield.
Ad5-vectored Coronavirus Disease-19 vaccine
This non replicating adenovirus type Ad5-vectored COVID-19 vaccine developed by CanSino Biological Inc. and Beijing Institute of Biotechnology has been found to elicit both cellular and humoral response in 95% of the participants after a single dose, with no serious adverse reactions reported.
Gamaleya's Sputnik V
Developed by Gamaleya Research Institute Epidemiology and Microbiology, Health Ministry of the Russian Federation, this non replicating adenovirus vaccine was the first registered COVID-19 vaccine in the market. The vaccine induced strong antibody and cellular immune response and was safe and well tolerated.
Ad26 COV2S Covid-19 vaccine
Janssen Pharmaceutical, the vaccine-making subsidiary of Johnson & Johnson, has developed this non-replicating viral vector vaccine which demonstrated overall protection of 66% against COVID-19 and 85% against moderate-to-severe disease, after a single dose of vaccine. The requirement of regular refrigeration for shipping and storage, and a single dose are potential benefits for distribution logistics.
Nucleic acid vaccines
Messenger RNA-1273 vaccine
This messenger RNA (mRNA)-based vaccine is developed by Moderna and NIAID and encodes the surface glycoprotein of SARS-CoV-2. The preliminary report suggested that it generated sufficient immune response in all the participants with no significant safety concerns. In the Phase 3 trial conducted at 99 centres across United States, the vaccine demonstrated 94.1% efficacy in preventing COVID-19.
BNT162b1 RNA vaccine
This candidate is an mRNA-based SARS-CoV-2 vaccine developed by BioNTech, Fosun Pharma and Pfizer, and encodes receptor binding domain of the SARSCoV-2 spike protein and confers 95% protection against COVID-19.
The WHO recommends that successful vaccines should have preferably 70% efficacy over 1 year and minimum 50% efficacy for at least 6 months.
| Findings from Vaccine Trials of Leading Candidates Globally|| |
The vaccines in different phases of development in India are given in [Table 1].
| Indian Scenario|| |
SII and the Indian Council of Medical Research (ICMR) are jointly conducting a Phase II/III, observer-blind, randomized, controlled study to determine the safety and immunogenicity of Covishield vaccine at 14 sites in India. This viral vector vaccine is developed by Oxford University-AstraZeneca and manufactured in India by SII and is stored at a temperature of 2°C–8°C. The Drugs Controller General of India (DCGI) granted emergency use authorisation (EUA) in January 2021. It was launched nationally on 16 January 2021.
India's indigenous COVID-19 vaccine was developed by Bharat Biotech in collaboration with the ICMR-National Institute of Virology. Phase I and II results showed tolerable safety outcomes and enhanced immune responses. Phase III trials are ongoing. It received restricted EUA by DCGI in January 2021.
It is a DNA plasmid vaccine expressing SARS-CoV-2 S protein, developed by Zydus Cadila Healthcare. It was found safe in Phase 1, and phase II is underway.
|Table 1: Indian landscape of coronavirus disease-19 vaccines development|
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The number of doses, dosage schedule and route of administration are listed in [Table 2].
| Doses and Route of Administration|| |
No serious adverse event related to the vaccine has been reported till now. In the various trial phases of different COVID-19 candidate vaccines, it was observed that vaccines are safe and well tolerated. However, minor adverse effects may be expected following vaccination. The local reactions include injection site pain, tenderness, warmth, redness, swelling, induration and itching. Systemic symptoms reported were malaise, myalgia, arthralgia, fatigue, nausea, headache, chills and fever.
| Safety Profile of Coronavirus Disease-19 Vaccines|| |
EUA is a mechanism to facilitate the availability and use of medical therapeutics, including vaccines during public health emergencies. The countries that have given EUA to COVID-19 vaccines is given in [Table 3]. As of 27 January 2021, there have been 1.03 cumulative COVID-19 vaccinations per 100 people globally. Maximum coverage has been achieved by Israel.
| Emergency Use Authorization|| |
|Table 3: Emergency Use Authorization of coronavirus disease-19 vaccines globally|
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SII, Global Access Vaccine Initiative, the Vaccine Alliance and the Bill and Melinda Gates Foundation have collaborated to provide COVID-19 vaccines, at a ceiling price of US$ 3 per dose, for low- and middle-income countries in 2021. Covishield vaccine was procured by the Government of India (GoI) at a cost of INR 200 per dose, while in the private market, the price is expected to be INR 1000 per dose. Bharat Biotech provided 16.50 lakh doses of Covaxin free of cost to GoI, while for the remaining 38.50 lakh doses, Bharat Biotech charged INR 295/dose, therefore considering the total procurement of 55 lakh doses, it amounted to INR 206 per dose.
| Cost Considerations|| |
To fast-track policy decisions and facilitate timely implementation of vaccine programme in India, a National Expert Group on Vaccine Administration for COVID-19 has been constituted. This thinktank is involved in the selection of suitable vaccine, its procurement, roll out plan of vaccine delivery: phase-wise delivery of the vaccine, prioritisation of groups, cold chain requirement: EVIN monitoring of cold chain and training plan of human resources. The vaccination programme was launched on 16 January 2021, with the first priority group being health-care workers. Other prioritised beneficiaries include frontline workers and population ≥50 years of age and <50 years with comorbidities such as diabetes, hypertension, cancer and lung diseases. COVID Vaccine Intelligence Work is the online portal for pre-registration, appointment confirmation, record maintenance, generation of certificate following vaccination and reporting of adverse events following immunisation.
| Coronavirus Disease-19 Vaccination Programme in India|| |
Children have higher ACE levels in serum compared to adults. Since ACE and ACE2 are inversely related, this difference reflects a lower degree of ACE2 in children. The vaccination programme does not include children as safety and immunogenicity in children has not been established yet. Some trials are underway to evaluate safety and immunogenicity of COVID-19 vaccine in children.
| Status of Coronavirus Disease-19 Vaccine in Paediatric and Adolescent Age Group|| |
As none of the COVID-19 vaccine trials are being conducted among the pregnant and lactating women, data regarding the safety and efficacy of the COVID-19 vaccine are unavailable. Hence, it is not recommended to offer these vaccines to this age group routinely. However, in case of pregnancy with comorbidities such as hypertension and diabetes and where the risk of having the morbidity and mortality due to COVID-19 infection is higher offering COVID-19 vaccine may be considered. ACOG recommends that COVID-19 vaccines should not be withheld from pregnant individuals. COVID-19 vaccines should be offered to lactating individuals similar to non-lactating individuals.
| Status of Coronavirus Disease-19 Vaccine Among Pregnant and Lactating Women|| |
COVID-19 vaccine can be given in cases of previous infection with SARS-CoV2 or history of chronic conditions (cardiac, neurological, pulmonary, metabolic, renal and malignancies). Similarly, immunodeficiency, HIV and immunosuppressive therapy are not contraindications; however, response to COVID-19 vaccines may be less in these individuals.
| Conditions where Coronavirus Disease-19 Vaccine can be Given|| |
Vaccination is avoided in people with immediate or delayed onset anaphylaxis or allergic reaction to Covid-19 vaccine, pregnant women, lactating women and children/adolescent aged under 18 years. It should be given with caution to persons with bleeding disorders (clotting factor deficiency, coagulopathy and platelet disorder) as it is given intramuscularly.
| Conditions where Coronavirus Disease-19 Vaccines should be Avoided|| |
COVID-19 vaccination should be deferred for 4–8 weeks after recover in people who have active symptoms of SARS-CoV-2 infection, recipients of anti-SARS-CoV-2 monoclonal antibodies or convalescent plasma and in those who are acutely unwell and hospitalised.
| Conditions where Coronavirus Disease-19 Vaccines should be Deferred|| |
It has been modelled that if the vaccine coverage is reached up to 65%–70%, the basic reproductive number, i.e., the number of persons infected by a COVID-positive person, can be reduced from the current 2/3–1/<1. This basic reproductive number of 1/<1 is not sufficient to sustain the pandemic and it will gradually be controlled. It will also enhance the herd immunity.
| Impact of Coronavirus Disease-19 Vaccine in Controlling the Pandemic|| |
Restricting the transmission of infection is a challenging task owing to its continuously evolving nature, and vaccines offer a potential solution to this. Development of COVID-19 vaccines has been accelerated globally. Phase I/II trials have demonstrated safety and immunogenicity, while preliminary results from phase III trials have shown vaccine efficacy ranging from 62% to 95%. This level of efficacy will be able to maintain the herd immunity levels, control the spread infection and limit pandemic. Efficacy in preventing COVID-19 infection and side effects over long term need to be monitored.
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Conflicts of interest
There are no conflicts of interest.
| Conclusions|| |
| References|| |
WHO Coronavirus Disease (COVID-19) Dashboard. Geneva: World Health Organization; 2020. Available from: https://covid19.who.int/.
[Last accessed on 2021 Jan 27].
Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV – A target for vaccine and therapeutic development. Nat Rev Microbiol 2009;7:226-36.
Krause P, Fleming TR, Longini I, Henao-Restrepo AM, Peto R, World Health Organization Solidarity Vaccines Trial Expert Group. COVID-19 vaccine trials should seek worthwhile efficacy. Lancet 2020;396:741-3.
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.
Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, et al
. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): A single-blind, randomised, controlled, Phase 2/3 trial. Lancet 2021;396:1979-93.
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 four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111.
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.
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.
Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al
. An mRNA vaccine against SARS-CoV-2-Preliminary report. N Engl J Med 2020;383:1920-31.
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.
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al
. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-15.
Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: A double-blind, randomised, phase 1 trial. Lancet Infect Dis 2021 S1473309920309427. https://doi.org/10.1016/S1473-3099(20)30942-7
Ministry of Health and Family Welfare. National Expert Group on Vaccine Administration for COVID-19 Deliberates on Strategy to Ensure COVID-19 Vaccines' Availability and Its Delivery Mechanism [Press Release] (August 12, 2020). Available from: https://www.pib.gov.in/PressReleasePage.aspx?PRID=1645363.
[Last accessed on 2021 Jan 27].
Skarstein Kolberg E. ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease. J Clin Virol 2020;126:104350.
Sinovac Research and Development Co., Ltd. A Randomized, Double-Blinded, Placebo-Controlled, Phase Ⅰ/Ⅱ Clinical Trial, to Evaluate the Safety and Immunogenicity of the SARS-CoV-2 Inactivated Vaccine (Vero Cell) in Healthy Population Aged 3-17 Years. US. National Library of Medicine. Available from: https://clinicaltrials.gov/ct2/show/NCT04551547.
[Last accessed on 2021 Jan 27].
[Table 1], [Table 2], [Table 3]