|Year : 2021 | Volume
| Issue : 4 | Page : 188-193
COVID-19 vaccines: A ray of hope
Neha Chand1, Rajani Mathur2, Shridhar Dwivedi3
1 Department of Clinical Research, Delhi Pharmaceutical Sciences and Research University, New Delhi, India
2 Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India
3 Department of Cardiology, National Heart Institute, East of Kailash, New Delhi, India
|Date of Submission||29-Jul-2021|
|Date of Decision||06-Aug-2021|
|Date of Acceptance||21-Sep-2021|
|Date of Web Publication||26-Oct-2021|
Dr. Shridhar Dwivedi
B-107, Sagar Apartment, Sector-62, Noida - 201 304, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Coronavirus-induced disease (COVID-19) has emerged as a dreaded pandemic which is a threat to the entire world. It all began in Wuhan, China, in December 2019 and rapidly spread over the world. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which is an enveloped virus single-stranded, positive-sensed ribonucleic acid virus that enters the host cell lungs via endocytosis or membrane fusion utilizing the ACE-2 receptor. The virus particles release and replicate into new progenies, which cause cytokine storm in some cases by releasing pro-inflammatory mediators into the lungs. It dominantly manifests as SARS-CoV-2 and eventually involves all systems of human body. As of July 15, 2021, approximately 189 million COVID-19-infected cases have been reported worldwide, with over 4 million individuals dying as a result. In India, so far there are approximately 31 million infected cases and 4 lakhs human lives have been lost. Various antivirals, antibiotics, corticosteroids, and other adjuvant therapies were being experimentally employed for COVID-19 prophylaxis and treatment. Many pharmaceutical companies have worked on COVID-19 vaccinations to stop the virus progression and transmission. In several countries, including India, the United States, and Russia, the COVID-19 vaccine has already been approved for human use. India has been able to produce two vaccines, namely Covaxin and Covishield, and launches a massive vaccination drive for people above 18 years adults. Till now, approximately 304 million subjects have been partially vaccinated and 73 million subjects are fully vaccinated. Various other COVID-19 vaccines are in Phase 3 of clinical development. Vaccines against COVID are a major tool against the progression and prevention of COVID-19.
Keywords: COVID-19, coronavirus, vaccines
|How to cite this article:|
Chand N, Mathur R, Dwivedi S. COVID-19 vaccines: A ray of hope. Indian J Med Spec 2021;12:188-93
| Introduction|| |
A vaccine is biological preparation that can produce an immune response in the host body. There are two types of immunity: Humoral immunity and cellular immunity. Humoral immunity is generated by B-cells which produces specific neutralizing antibodies to extracellular pathogen, whereas cellular immunity is generated by activating helper CD4+ and CD8+ T-cells. Vaccines are being developed for preventing the subsequent infection due to a particular pathogen. Currently, lots of companies are hunting for vaccines as it is the most effective method to produce harmless mass immunization against COVID-19. On January 11, 2020, upon revelation of the genetic sequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), both pharmaceutical companies and academic institutes became engaged in vaccine development and out of which some even reached to clinical phases., Normally, the vaccine takes years to develop, but the situation of SARS-CoV-2 pandemic shifts the vaccine paradigm from years to months leading to a parallel release of much candidature in market. There are different types of vaccines being produced:
DNA plasmid vaccines
These vaccines can induce innate immunity. As the genetic makeup of SARS-CoV-2 is revealed, the development of vaccine becomes possible. The biotechnologically developed complementary sequence of DNA can be assembled with plasmids or small extrachromosomal double-stranded DNA fragment that has the capability for expression of antivirus gene. DNA vaccines are stable and tolerable, but once the vaccine reaches to host immune system, there is a possibility that the vector may cross the cellular membrane and interact with humans leading to the generation of antibody. However, there is no such vaccine approval till now.,
Messenger ribonucleic acid vaccines
These vaccines are incorporated into messenger ribonucleic acid (mRNA) coding for the SARS-CoV-2 spike protein. After injecting mRNA in healthy persons, it stimulates host cell machinery to synthesize more mRNA and proteins. These viral proteins are recognized as “non-self” by the immune system which can replicate using host machinery and confer both humoral and cellular immunity to the host body.
Due to high instability under normal temperature, various methods and strategies such as capping, lipid nanoparticles, polyethylene glycol (PEG) nanoparticles, polymer liposomes, nanoemulsions, polysaccharide particles, and protamine liposomes are employed to increase the stability of vaccine., BioNTech (NCT04368728) and Pfizer (Phase 3) are collaborating to develop a series of mRNA-based COVID19 vaccines based on this approach. In the Phase 1/2, two different vaccines consisting of lipid nanoparticle-formulated and nucleoside-modified mRNA formulation are tested to produce RBD-binding IgG and neutralizing antibodies in 45 recipients of age 18–55 years. They had taken 10 μg, 30 μg, or 100 μg dose twice intramuscularly at 21 days apart. The first candidate due to reactogenicity was not able to move forward, but the second one goes to successive phases and is able to reach Phase 3. In this phase, around 44000 individuals (aged 18–85 years) are currently recruited in the USA. One potential issue for vaccine deployment is that a storage temperature of −80°C is required which creates some logistic issues., UK, FDA, and Canadian regulatory agency has approved the use of mRNA vaccine developed by BioNTech and Pfizer, whereas Moderna mRNA vaccine recently by has got an emergency use authorization by FDA.
Viral vector vaccines
These vaccines are produced via genetic engineering, where the viral antigen encoded material is placed in vector leading to cell-mediated immune response. It has some of the major qualities such as highly specific nature, efficiency of high gene transduction, ability to reach the target, and produce good quality of response. It produces prolong action with a high level of neutralizing capability, which makes it a potential candidate for prophylactic therapy as these vaccines induce cytotoxic T-cells which eventually eliminates the virus infected cells from host body by permitting the expression of intracellular genes and producing cellular immunity. “Sputnik-V” is an adenoviral vector-based vaccine developed by Russian company “Gamaleya Research Institute of Epidemiology and Microbiology” and is currently being approved in Russia for SARS-CoV-2. Another company, CanSino Biologics (NCT04526990), is working hand to hand with an academy of military medical sciences to produce a recombinant adenovirus serotype 5-vectored vaccine which initiated Phase 3 trials from September 2020. The 40,000 participates of 18–60 years are being recruited. The information on storage conditions is likely to be the same as adenovirus vectors vaccine which includes either refrigeration or storage at −20°C.
These vaccines are produced by the traditional method, which involves killing microorganisms either through physical/chemical processes or weakened under laboratory but able to generates a cascade of immunization processes in the host., Optimum condition is required for the preparation. However, excess treatment degrades antigenic epitopes, resulting in production of lesser neutralizing antibody response and faulty protection upon challenge with a live virus. Moreover, if complete inactivation of virus does not occur, then the future eruption of the disease can take place from the vaccine itself. Wuhan Institute of Biological Products and Beijing Institute of Biological Products in collaboration with Sinopharm are also working toward the development of inactivated vaccines. The Chinese inactivated vaccines are now moving forward toward Phase 3 trial and enrolled 21,000 healthy volunteers as well as some health-care personnel or groups who are at high risk of getting infected. Most of the trials were performed in the United Arab Emirates and many other countries. CoronaVac developed by Chinese company Sinovac Life Sciences got emergency use authorization in Brazil, UAE, Indonesia, and Turkey.,
These vaccines contain viral antigenic species which are responsible for eliciting an immune response. The subunit vaccine exhibits low immunogenicity and requires assistance to ameliorate the biological half-life of reactive components and vaccine-mediated immunity. For producing SARS-CoV-2 vaccine, spike protein is a good target for its development. The spike protein resides in two states: Prefusion and postfusion state that helps in retaining its surface conformation and profile to maintain the epitopes to enhance neutralizing antibody response with revamping efficacy. The Novavax pharmaceutical company has succeeded in making a nanoparticle-based NVX-CoV2373 candidate which is based on this method. The spike protein derived from the Baculovirus system assisted with matrix-M to improve response by producing high titer of antibodies against the virus. This vaccine is currently in Phase 2 (last updated on 28 October 2020).
The vaccines approved for use in India are mentioned in [Table 1]. Repurposed vaccines are those vaccines which are being used for preventing other diseases rather than recommended purpose. Due to reprogramming techniques, live attenuated Bacillus Calmette − Guérin (BCG) vaccine has been found to reduce susceptibility for respiratory tract infection. Till now, there are no available studies stating that BCG vaccine will provide protection against COVID-19. Some of the studies, NCT04327206, NCT04348370, NCT04350931, NCT04362124, and NCT04369794, are ongoing to investigate the effectiveness of BCG in COVID-19. Most of the studies even reached to Phases 3 or 4. There is only one ongoing study (Phase 4) evaluating the effect of inhaling inactivated mycobacterium vaccine in protecting against COVID-19 (Chinese Clinical Trials Register ChiCTR2000030016).
It refers to the indirect protection of susceptible individuals against specific infection when a large number of human population becomes immune against a pathogen. It is slightly different from the acquired immunity. Herd immunity is established by the expansion of individual immunity to population level, while acquired immunity is established at the individual level either acquired through natural pathogen or by taking a vaccine. There are many factors that permit the development of herd immunity such as immune population titer, length and duration of immune response, and stability of viral epitopes. The history of herd immunity shows many examples such as smallpox, measles, rubella, and pertussis when the population is already immune to deadly infection.
Herd immunity would be effective if a vaccine is provided to the whole population of the world at the same instant. However, the development of herd immunity across all geographical areas and locations will be difficult due to the differences in the availability and affordability of the vaccine. In addition, getting long-term immunity against SARS-CoV-2 is still uncertain.
| Immunostimulation by Vaccines against COVID-19|| |
The body must first detect the threat, whether it is a pathogenic agent or an immunization, as with any immune system challenge. The innate immune system is usually responsible for the initial detection, though B-cells may also be involved. When the immune system detects epitopes on antigens, the detection process begins. Epitopes are tiny subregions of antigens that mimic other antigens.
Vaccines contain weakened or inactive components of a certain organism (antigen) that cause the body to respond with an immune response. Rather than the antigen itself, newer vaccinations contain the blueprint designed to generate antigens. This weakened version will not cause disease in the person receiving the vaccine, regardless of whether the vaccine is made up of the antigen itself or the blueprint for the body to produce the antigen. It will, however, prompt their immune system to respond similarly to how it would have responded to the pathogen in the first place. Several vaccines require successive doses separated by weeks or months. This is sometimes required to allow for the establishment of memory cells and the creation of long-lasting antibodies. In this approach, the body is trained to resist a specific disease-causing organism, and the pathogen's memory is built up so that it may be quickly combated if and when it is exposed in the future.
| Vaccination for Vulnerable Groups|| |
The Government of India on June 25, 2021, has approved COVID-19 vaccination for pregnant women, as guidelines regarding COVID-19 vaccination of pregnant women group given by the Ministry of Health suggests, along with lactating mothers, pregnant women can and should be vaccinated against coronavirus. However, they should be fully informed that the long-term adverse reactions and the safety of the vaccine have not been yet established and they should follow the 30 min of inhospital observation rule post vaccination. As per guidelines, it can be taken at any trimester of pregnancy. Moreover, there is a need of COVID vaccine for pregnant females than nonpregnant women, as there is a higher risk of severe disease after infection, resulting in ICU admission, mechanical ventilation, and death in pregnant women than nonpregnant women, it is even higher in pregnant women with coexisting illnesses such as diabetes, hypertension, and obesity. Pregnancy complications such as preterm birth, cesarean delivery, and preeclampsia can also be faced with COVID-19 during pregnancy. Although 90% of pregnant women recover without needing to be hospitalized if they are infected with the virus, rapid worsening in health may occur in a minority. Symptomatic pregnant women, however, appear to be at risk of serious illness and death. Pregnant women, like other patients, will require hospitalization in case of serious illness. Even an Indian study from ICMR emphasized that the second wave of pandemic hit pregnant and postpartum women more severely compared to the first wave. Case fatality rate among pregnant women and postpartum women was 5.7% during the second wave in comparison to 0.7% in the first wave.
USA mRNA vaccine suggests a robust safety data when study was conducted on 35,691 pregnant women of 16–54 years of age. Of these ladies, 86.5% had a known pregnancy at the time of vaccination and 13.5% reported a positive pregnancy test after vaccination. Out of 35,651 women, 29% received vaccine in the first trimester, 43% in the second trimester, and 26% in the third trimester. The observation was also paid on the postvaccination delivery cases indicative of no neonatal deaths and among live-born infants, the incidences of preterm birth (9.4%), small size for gestational age (3.2%), and congenital anomalies (2.2%) were consistent with those expected on the basis of published literature in prepandemic period.
ICMR states that as second COVID wave has hit India hard with lakhs infected and thousands dead daily but the third wave may be more deadly which can attack children below 18 years of age, particularly due to mutation of the virus; however, there is a lack of safety and efficacy data for the vaccination of 18 years or less children. Bharat biotech has been conducting a trial on 525 children between 2–18 years of age. The upcoming third wave demands for a necessary increase in the vaccination pace and widening of vaccine net.
| COVID Variants|| |
The working definitions may be changed periodically due to the ongoing evolution of the virus that causes SARS-CoV-2 and ongoing advances in understanding the effects of variations. In accordance with the WHO Technical Advisory Group on Viral Evolution variants that provide a reducing risk relative to other circulating variants can be reclassified. A SARS-CoV-2 variant that fits the definition of a 'variant of interest' (VOI) [Table 2] and has been shown to be linked with one or more of the following modifications at a level of global public health significance through a comparative assessment: increased transmissibility or a negative shift in COVID-19 epidemiology or an increase in virulence or a change in clinical illness presentation or reduced efficacy of public health and social interventions, as well as available diagnostics, vaccinations, and treatments is termed as a variant of concern (VOC) [Table 3]. Currently, we have four VOCs: alfa, beta, gamma, and delta originated from the United Kingdom, South Africa, Brazil, and India, respectively.
Variant of interest causes a genetic mutation associated with changes in receptor binding, lower neutralization by antibodies developed against previous infection or vaccination, reduced treatment efficacy, potential diagnostic impact, or projected increase in transmissibility or disease severity. Currently, Eta B.1.525, Iota B.1.526, Kappa B.1.617.1, and lambda C.37 are designed VOI originating from multiple countries such as the United States of America, India, and Peru, respectively.
According to a new study conducted in the United Kingdom, Oxford AstraZeneca vaccinations, which are made and delivered in India under the brand name Covishield, provide protection that may last a lifetime. According to the study, the vaccine not only builds antibodies against the SARS-CoV-2 virus but also creates “training camps” in the body, allowing T-cells to look for and destroy other variants. The T-cells that emerge from these cellular training camps appear to be in excellent shape. Adenoviruses have spent a long time co-evolving with humans, learning a lot about the human immune system in the process. Adenoviruses have the potential to infiltrate long-lived tissue cells, according to the findings of the study. These cells, known as fibroblastic reticular cells, can serve as “training grounds” for T-cells.
The latest findings support recent research that found the Oxford Astrazeneca vaccine to be more successful in generating T-cells than the mRNA vaccines from Pfizer and Moderna. Adenovirus vaccinations have been given to millions of people all over the world. The ultimate goal of these vaccinations is to use antibodies and T-cells to provide long-term immune system protection.
The coronavirus is a symbol of the Kaurava dynasty of Mahabharata fame. The hospital is the battlefield and the doctors, nurses, and other health-care workers fighting against this calamity are our present Arjuna. Just as Arjuna had become confused on the rationale of fighting against his family members in the battlefield in the Mahabharata, similarly, today, seeing the highly contagious and lethal nature of COVID, the doctors were very concerned initially about the safety of themselves and their families.
The role of Krishna is being played by universally accepted scientific principles of medical science and ethics of medicine laid down by stalwarts such as Hippocrates. Just as Arjuna's first duty was to fight the war like a warrior without worrying about the consequences. Similarly, the doctors are treating patients suffering from corona as per the standard guidelines issued by WHO and ICMR with conviction and dedication taking preventive precautions like donning up PPE kits and observing strict sanitary measures in the present situation. As per WHO details, one lakh and fifty thousand health-care people have lost their life due to COVID so far. Needless to say, during this Mahabharata, we faced many other social inequalities apart from COVID-like the economic-social gap between the village and city, the disparity between the rich and the poor people in their own country. It is a matter of satisfaction that most of our young doctors and other attendants playing the role of Arjuna are at war with ethical principles. These health-care workers such as doctors, nurses, paramedics, sanitary workers, and ambulance drivers who are on the path of duty and serving the patients wholeheartedly have now been fully vaccinated.
| Conclusion|| |
Due to the sudden emergence of coronavirus-induced pandemic, the world has suffered a major crisis in health-care systems. The deadly coronavirus has been responsible for more than one million deaths worldwide. Elderly population and those with comorbidities such as diabetes, hypertension, CAD, and COPD have higher mortality than otherwise healthy population. During the start of the pandemic, only symptomatic care was provided to the patients. Later, a lot of drugs were clinically repurposed to check their effectiveness for COVID-19 treatment. However to have a long-term immunization from COVID-19, discovery and development of vaccines against COVID-19 was necessary for public welfare and to break the chain of the virus and to reduce the severity of the disease. Vaccine is a biological preparation that is capable to act as a prophylactic agent against a specific disease or infection. The vaccine plays an effective role for checking the disease spread. The first-ever marketed COVID19 vaccine was “SPUTNIK V,” followed by “Corona Vac,” subsequently mRNA vaccines from Pfizer and Moderna were given a chance to reach globally. Moreover, India's “Covishield” and Bharat Biotech's “Covaxin” also got approval for human use. Other vaccines in the phase 3 trial, such as nucleic acid vaccines and subunit vaccinations, are also showing promising results; hence, they are about to reach the market. However, due to its mutations at periodic intervals, long-term immunity against SARS-CoV-2 remains uncertain.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]