Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. Older people and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness.Covid vaccinations play a major role in curbing the spread of the COVID 19 Virus. Vaccines contain tiny fragments of the disease-causing organism or the blueprints for making the tiny fragments. They also contain other components to keep the vaccine safe and effective.
VACCINE COMPONENTS:
i. ANTIGEN
All vaccines contain an active component (the antigen) which generates an immune response, or the blueprint for making the active component. In other words, any substance that induces the immune system to produce antibodies against it is called an antigen. The antigen may be a small part of the disease-causing organism, like a protein or sugar, or it may be the whole organism in a weakened or inactive form.
ii. ADJUVANT
An adjuvant is a substance that enhances the immune system’s response to the presence of an antigen. They are commonly used to improve the effectiveness of a vaccine. Generally, they are injected alongside an antigen to help the immune system generate antibodies that fight the antigen.
iii. PRESERVATIVES
Preservatives prevent the vaccine from becoming contaminated once the vial has been opened. Some vaccines do not have preservatives because they are stored in one-dose vials and are discarded after the single dose is administered.
iv. STABILIZERS
Stabilizers prevent chemical reactions from occurring within the vaccine and keep the vaccine components from sticking to the vaccine vial. Stabilizers can be sugars like lactose, sucrose, amino acids (glycine), gelatin, and proteins.
v. SURFACTANTS
Surfactants keep all the ingredients in the vaccine blended together. They prevent settling and clumping of elements that are in the liquid form of the vaccine.
vi. DILUENT
A diluent is a liquid used to dilute a vaccine to the correct concentration immediately prior to use. The most commonly used diluent is sterile water.
vii. RESIDUALS
Residuals are the remaining minute quantities of substances that have been used during the manufacturing or production process of individual vaccines. Residuals depend on the process used, which may have involved cell culture mediums, egg proteins or other animal derived ingredients, culture cells, yeast, antibiotics such as neomycin or streptomycin, or inactivating agents such as formaldehyde. These substances are only present as traces and often measured as parts per million and parts per billion in the final vaccine formulation.
What are antibodies?
ILLUSTRATION OF AN ANTIBODY
Antibody, also called immunoglobulin, is a protective protein produced by the immune system in response to the antigen. Antibodies recognize and latch onto antigens in order to remove them from the body. When an alien substance enters the body, the immune system is able to recognize it as foreign because molecules on the surface of the antigen differ from those found in the body. To eliminate the invader, the immune system calls on a number of mechanisms, including one of the most important, the antibody production. Antibodies are produced by specialized white blood cells called B-lymphocytes or B cells. When an antigen binds to the B-cell surface, it stimulates the B cell to divide and mature into a group of identical cells called a clone. The mature B cells, called plasma cells, secrete millions of antibodies into the bloodstream and lymphatic system. As antibodies circulate, they attack and neutralize antigens that are identical to the one that triggered the immune response. Antibodies attack antigens by binding to them. By attaching themselves to some invading microbes, other antibodies can render such microorganisms immobile or prevent them from penetrating body cells.
How do vaccines help?
WORKING MECHANISM OF VACCINES
Vaccines contain weakened or inactive parts of a particular organism (antigen) that triggers an immune response within the body. Newer vaccines contain the blueprint for producing antigens. Regardless of whether the vaccine is made up of the antigen itself or the blueprint so that the body will produce the antigen, this weakened version will not cause the disease in the person receiving the vaccine, but it will prompt their immune system to respond much as it would have on its first reaction to the actual pathogen. Some vaccines require multiple doses, given weeks or months apart. This is sometimes needed to allow for the production of long-lived antibodies and development of memory cells. In this way, the body is trained to fight the specific disease-causing organism, building up memory of the pathogen so as to rapidly fight it when exposed in the future.
There are four categories of COVID vaccines - WHOLE VIRUS, PROTEIN SUBUNIT, VIRAL VECTOR and NUCLEIC ACID (RNA AND DNA)
WHOLE VIRUS VACCINES:
This vaccine uses inactivated virus to trigger an immune response, without the virus infecting the body. When the body comes in contact with the weakened virus, the immune system produces antibodies and T cells to attack it. In the process, specialised memory cells take note of the specific antigen so that the next time the body comes in contact with the same virus, the immune system can fight it.
PROTEIN SUB-UNIT VACCINES:
Instead of using the whole virus, this vaccine uses fragments of it like the spike protein. These fragments produce a weaker immune response. Hence, these vaccines often include chemical agents called adjuvants, which are designed to stimulate a stronger immune response. These sub-unit vaccines have the advantage of being relatively cheap ad easier to produce.
VIRAL VECTOR VACCINES:
Viral vector-based vaccines differ from most conventional vaccines where they do not actually contain antigens, but rather use the body’s own cells to produce them. They do this by using a harmless modified virus (the vector) to deliver genetic code of the virus into the body cells. Once injected into the body, these vaccine viruses begin infecting the cells and insert their genetic material – including the antigen gene – into the cell’s nuclei. Human cells manufacture the antigen as if it were one of their own proteins and this is presented on their surface alongside many other proteins. When the immune cells detect the foreign antigen, they mount an immune response against it.This has the advantage of triggering a strong cellular immune response by T cells as well the production of antibodies by B cells. Oxford-AstraZeneca is the first viral vector vaccine to be approved for Covid-19.
NUCLEIC ACID VACCINES:
This vaccine also involves inserting the genetic material of the virus it the cell to produce antigens. This is done either by attaching it to a molecule or by forcing into the cells by a gene gun. This is a relatively new technology
VACCINE EVALUATION:
Each vaccine under development must first undergo screenings and evaluations to determine which antigen should be used to invoke an immune response. This preclinical phase is done without testing on humans. An experimental vaccine is first tested in animals to evaluate its safety and potential to prevent disease. If the vaccine triggers an immune response, it is then tested in human clinical trials in three phases.
Phase 1
The vaccine is given to a small number of volunteers to assess its safety, confirm if it generates an immune response, and determine the right dosage. Generally, in this phase vaccines are tested in young, healthy adult volunteers.
Phase 2
The vaccine is then given to several hundred volunteers to further assess its safety and ability to generate an immune response. Participants in this phase have the same characteristics (such as age, sex) as the people for whom the vaccine is intended. There are usually multiple trials in this phase to evaluate various age groups and different formulations of the vaccine. A group that did not get the vaccine is usually included in phase as a comparator group to determine whether the changes in the vaccinated group are attributed to the vaccine, or have happened by chance.
Phase 3
The vaccine is next given to thousands of volunteers and compared to a similar group of people who did not get the vaccine, but received a comparator product, to determine if the vaccine is effective against the disease it is designed to protect against and to study its safety in a much larger group of people. Most of the time phase three trials are conducted across multiple countries and multiple sites within a country to assure the findings of the vaccine performance apply to the various populations.
During phase two and phase three trials, the volunteers and the scientists conducting the study are shielded from knowing which volunteers had received the vaccine being tested or the comparator product. This is called “blinding” and is necessary to assure that neither the volunteers nor the scientists are influenced in their assessment of safety or effectiveness by knowing who got which product. After the trial is over and all the results are finalized, the volunteers and the trial scientists are informed who received the vaccine and who received the comparator. When the results of all these clinical trials are available, a series of steps is required, including reviews of efficacy and safety for regulatory and public health policy approvals. Officials in each country closely review the study data and decide whether to authorize the vaccine for use. A vaccine must be proven safe and effective across a broad population before it will be approved and introduced into a national immunization programme.
What is vaccine efficacy?
Vaccine efficacy is the percentage reduction of disease in a vaccinated group of people compared to an unvaccinated group, using the most favourable conditions. Vaccine efficacy differs from vaccine effectiveness. Vaccine efficacy shows how effective the vaccine could be given in ideal circumstances and vaccine effectiveness measures how well a vaccine performs when it is used in routine circumstances in the community. If a vaccine has, for example, 70% efficacy, it means a person vaccinated in a clinical trial is around two-thirds less likely to develop the disease than someone in the trial who did not get the vaccine.
What is an Emergency Use Authorization (EUA)?
An Emergency Use Authorization (EUA) is a mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies, such as the current COVID-19 pandemic. Under a EUA, FDA may allow the use of unapproved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met. Taking into consideration input from the FDA, manufacturers decide whether and when to submit an EUA request to FDA.Once submitted, FDA will evaluate an EUA request and determine whether the relevant statutory criteria are met, taking into account the totality of the scientific evidence about the vaccine that is available to FDA. For a EUA to be issued for a vaccine, FDA must determine that the known and potential benefits outweigh the known and potential risks of the vaccine. Part of FDA’s evaluation of a EUA request for a COVID-19 vaccine includes, evaluation of the chemistry, manufacturing, and controls information for the vaccine. Sufficient data should be submitted to ensure the quality and consistency of the vaccine product.
As of April 2021, 16 vaccines are authorized by at least one national regulatory authority for public use:
v Two RNA vaccines -Pfizer–BioNTech and Moderna
v Seven conventional inactivated vaccines BBIBP-CorV, CoronaVac, Covaxin, WIBP-CorV, CoviVac, Minhai-Kangtai and QazVac
v Five viral vector vaccines -Sputnik Light, Sputnik V, Oxford–AstraZeneca, Convidecia, and Johnson & Johnson
v Two protein subunit vaccines -EpiVacCorona and RBD-Dimer
NUCLEIC ACID VACCINES:
Pfizer–BioNTech
The Pfizer–BioNTech COVID-19 vaccine is an mRNA-based COVID-19 vaccine. On May 10, 2021, the FDA expanded the emergency use authorization for the Pfizer-BioNTech COVID-19 Vaccine to include adolescents 12 through 15 years of age. BioNTech, a German company, developed the vaccine and collaborated with Pfizer, an American company, for support with clinical trials, logistics, and manufacturing. The mRNA is delivered to the body's cells by lipid nanoparticles, which instructs the cells to generate the spike protein found on the surface of the novel coronavirus that initiates infection. Instructing cells to generate the spike protein spurs an immune response, including generation of antibodies specific to the SARS-CoV-2 spike protein. Phase 3 study through March 13, 2021, showing the Pfizer-BioNTech COVID-19 vaccine, BNT162b2, was 91.3% effective against COVID-19, measured seven days through up to six months after the second dose.
Moderna
The Moderna COVID‑19 vaccine, codenamed mRNA-1273, is developed by Moderna Inc. (an American pharmaceutical and biotechnology company), the United States National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA). On December 18, 2020, the U.S. Food and Drug Administration issued an emergency use authorization for its use. It is used in people aged 18 years and older. It is authorized for use at some level in 45 countries including the United States, Canada, the European Union, the United Kingdom, Israel, and Singapore. High efficacy is achieved with full immunization, two weeks after the second dose, and was evaluated at 94.1%: at the end of the vaccine study that led to emergency authorization in the USA
WHOLE VIRUS VACCINES:
Sinopharm BBIBP-CorV
Sinopharm BBIBP-CorV also known as the Sinopharm COVID-19 vaccine is one of two inactivated virus COVID-19 vaccines developed by Sinopharm's Beijing Institute of Biological Products. Sinopharm's SARS-CoV-2 strain was isolated from a patient in the Jinyintan Hospital, Wuhan, China. The virus was cultivated in a qualified Vero cell line for propagation, and the supernatant of the infected cells was inactivated with β-propiolactone (1:4000 vol/vol at 2 to 8 °C) for 48 hours. Following clarification of cell debris and ultrafiltration, the second β-propiolactone inactivation was performed in the same conditions as the first inactivation. The vaccine was adsorbed to 0.5-mg alum and packed into prefilled syringes in 0.5-mL sterile phosphate-buffered saline without preservative. On December 31, 2020, China's National Medical Products Administration announced the experimental vaccine, developed by State-owned Sinopharm, was approved. On May 7, 2021, the WHO announced the vaccine's approval. In April 2021, a study conducted by the Abu Dhabi Public Health Centre found the vaccine was 93% effective in preventing hospitalization and 95% effective against admission to intensive care.
WIBP-CorV
WIBP-CorV is another inactivated virus vaccine developed by Sinopharm. Peer-reviewed results show WIBP-CorV 72.8% effective against symptomatic cases and 100% against severe cases. According to New York Times, the WIBP-CorV is only approved for limited use in United Arab Emirates.
CoronaVac
CoronaVac also known as the Sinovac COVID-19 vaccine is an inactivated virus COVID-19 vaccine developed by the Chinese company Sinovac Biotech. CoronaVac is being used in vaccination campaigns in various countries in Asia, South America, North America, and Europe. Final Phase III results from Turkey announced on 3 March 2021 showed an efficacy of 84%.
CoviVac
CoviVac is an inactivated virus-based COVID-19 vaccine developed by the Chumakov Centre, which is an institute of the Russian Academy of Sciences. It was approved for use in Russia in February 2021, being the third COVID-19 vaccine to get approval in Russia. It has not yet gone through a phase III clinical trial as of early March 2021.
Minhai-Kangtai
Minhai COVID-19 vaccine is developed by Minhai Biotechnology Co. and Kangtai Biological Products Co. Ltd. On May 14, 2021, the fourth inactivated Chinese Vaccine received authorisation for emergency use.
QazVac
QazCovid-in, commercially known as QazVac, is developed by the Research Institute for Biological Safety Problems in Kazakhstan. QazVac is currently in Phase 3 of the Clinical Trial, which is expected to be fully completed by July 9. The administration of the vaccine for the general population began at the end of April 2021.
VIRAL VECTOR VACCINES:
Sputnik Light
Sputnik Light is a single dose COVID-19 vaccine developed by the Gamaleya Research Institute of Epidemiology and Microbiology. Sputnik Light is the first component of Sputnik V which means, it is the first dose of the Sputnik V vaccine. The institute says this version, with an effectiveness of 79.4%, would be ideally suited for areas with acute outbreaks, allowing more people to be vaccinated quickly.
Oxford–AstraZeneca
The Oxford–AstraZeneca COVID-19 vaccine, codenamed AZD1222 and sold under the brand names Covishield and Vaxzevria among others, is a viral vector vaccine. Developed by Oxford University and AstraZeneca, it is given by intramuscular injection. The vector used is the modified chimpanzee adenovirus ChAdOx1.The efficacy of the vaccine is 76.0% at preventing symptomatic COVID-19 beginning at 22 days following the first dose and 81.3% after the second dose. Two versions of the vaccine, produced by AstraZeneca-SKBio (Republic of Korea) and the Serum Institute of India have been listed for emergency use by WHO. The EMA has thoroughly assessed the data on the quality, safety and efficacy of the vaccine and has recommended granting a conditional marketing authorisation for people aged 18 and above.
Convidecia
AD5-nCOV, trade-named Convidecia, is a single-dose viral vector vaccine for COVID-19 developed by CanSino Biologics, a Chinese vaccine company. In February 2021, global data from Phase III trials and 101 COVID cases showed that the vaccine had a 65.7% efficacy in preventing moderate symptoms of COVID-19, and 91% efficacy in preventing severe disease. While the efficacy rates were lower than the Pfizer–BioNTech and Moderna vaccines, its single-dose regimen and normal refrigerator storage requirement (2 to 8 °C) could make it a favourable option for many countries.
Johnson & Johnson
On February 27, 2021 Johnson & Johnson received Emergency Use Authorization (EUA) for its single-dose COVID-19 vaccine, developed by the Janssen Pharmaceutical Companies of Johnson & Johnson, to prevent COVID-19 in individuals 18 years of age and older. This decision was based on the totality of scientific evidence, including data from the Phase 3 study that demonstrated the vaccine was 85 percent effective in preventing severe disease across all regions studied, and showed protection against COVID-19 related hospitalization and death, beginning 28 days after vaccination.
PROTEIN SUBUNIT VACCINES:
EpiVacCorona
EpiVacCorona is a peptide-based vaccine developed by the VECTOR centre of Virology, Russia. It consists of three chemically synthesized peptides (short fragments of a viral spike protein) that are conjugated to a large carrier protein. This protein is a fusion product of a viral nucleocapsid protein and a bacterial MBP protein. The third phase of a clinical trial was launched in November 2020 with more than three thousand participants. It is assumed it will be completed in August 2021. The vaccine has received vaccine emergency authorization in a form of government registration and is available for vaccination outside the clinical trials.
RBD-Dimer
ZF2001, trade-named ZIFIVAX, is an adjuvant protein subunit vaccine developed by Anhui Zhifei Longcom in collaboration with the Institute of Microbiology at the Chinese Academy of Sciences. As of December 2020, the vaccine was in Phase III trials with 29,000 participants in China, Ecuador, Malaysia, Pakistan, and Uzbekistan. It is administered in three doses over a period of two months.ZF2001 was first approved for use in Uzbekistan and later China. Phase II results published in The Lancet on the three-dose administration showed seroconversion rates of neutralizing antibodies of between 92% to 97%.
What is a vaccine patent?
Patents give vaccine makers exclusive rights to manufacture the shot they developed. They are also free to charge a price that covers their research and development costs, but deep profit margins can be controversial during times of crisis, such as the ongoing Covid pandemic. A patent waiver would allow any company with the required capacity to start manufacturing the shot, even without an agreement with the original developer.
India and South Africa’s proposal suggests that patents on different Covid vaccines be waived until there is widespread vaccination and most parts of the world develop herd immunity. In need of accelerated vaccine manufacturing and production across the globe, companies have offered different alternatives to patent waivers. For instance, AstraZeneca, in June 2020, shared their licence so that vaccines can be manufactured at multiple sites to increase production. It forged agreements with Epidemic Preparedness Innovations (CEPI), Gavi the Vaccine Alliance and the Serum Institute of India. In October 2020, Moderna released a statement where it announced that it would not enforce Covid-related patents. In January 2021, French Pharmaceutical Company Sanofi announced that it had arrived at an agreement with BioNTech to supply its vaccines to the European Union. The French company will help manufacture 125 million doses of the shot. In April 2021, Russia announced that it would be offering free technological transfer of its Covid-19 vaccine, Sputnik V, to India.
COVID-19 VACCINATION IN INDIA
India began administration of COVID-19 vaccines on 16 January 2021 .As of 27 May 2021, India has administered 205,720,660 doses overall, including first and second doses of the currently approved vaccines. Two vaccines received approval for emergency use in India at the onset of the programme; Covishield, a brand of the Oxford–AstraZeneca vaccine manufactured by the Serum Institute of India and Covaxin, which was developed by Bharat Biotech. In April 2021, the Indian government approved the Russian Sputnik V vaccine as a third vaccine, which began use in May 2021.
The first phase of vaccination involved health workers and frontline workers including police, paramilitary forces, sanitation workers, and disaster management volunteers. By 1 March 2021, 14 million healthcare and frontline workers had been vaccinated.
The second phase of the vaccine rollout covered all residents over the age of 60, residents between the ages of 45 and 60 with 1 or more qualifying comorbidities, and any health care or frontline worker that did not receive a dose during phase 1. Online registration began on 1 March via the Aarogya Setu app and Co-WIN.
On 19 April, it was announced that the next phase of the vaccine program would begin on 1 May, extending eligibility to all residents over the age of 18. On 13 May, the DCGI approved phase two and phase three trials of Covaxin among children. On 14 May, health officials projected that based on the anticipated approval of additional vaccine options; it could receive at least 2.17 billion more vaccine doses from August to December 2021.
COVAXIN
COVAXIN is India's first indigenous COVID-19 vaccine by Bharat Biotech, which has been developed in collaboration with the Indian Council of Medical Research (ICMR) and National Institute of Virology (NIV). The vaccine is developed and manufactured in Bharat Biotech's BSL-3 (Bio-Safety Level 3) high containment facility. It is an inactivated vaccine, which has been prepared on a tried and tested platform of dead viruses. The Central Drugs and Standards Committee (CDSCO) (India’s drug regulator), issued an emergency approval for Covaxin on 3 January 2021, even though phase III clinical trials were still ongoing .This vaccine is developed with Whole-Virion Inactivated Vero Cell-derived technology. Covaxin includes adjuvants, which are added to the vaccine to increase and boost its immunogenicity. Analysis from the National Institute of Virology indicates that vaccine-induced antibodies can neutralize the UK variant strains and other heterologous strains.
It is recommended that the second dose of COVAXIN should be administered in the interval of 4 to 6 weeks from the date of first dose administration. The side effects include injection site pain, headache, fatigue, fever, body ache, abdominal pain, nausea and vomiting, dizziness-giddiness, tremor, sweating, cold, cough and injection site swelling.
COVISHIELD
Covishield vaccine has been developed by Oxford University in collaboration with AstraZeneca. In India, Pune-based Serum Institute of India (SII), the world's largest vaccine manufacturer, has a licence to produce the shot. The vaccine is made by taking a common cold virus called an adenovirus from chimpanzees and deleting about 20% of the virus’s instructions.
The possible adverse events following immunisation are injection site tenderness, injection site pain, headache, fatigue, myalgia, malaise, pyrexia, chills and arthralgia, and nausea. The recommended interval is 4 to 8 weeks while an interval of 6 to 8 weeks gives an enhanced protection.
SPUTNIK V
Russia's Sputnik V works in a way similar to the Oxford-AstraZeneca jab. Sputnik V gives around 92% protection against Covid-19 (late stage trial results published in The Lancet reveal). Sputnik V's approval came as India overtook Brazil to become the country with the second-highest number of cases globally.
Unlike other similar vaccines, the Sputnik jab uses two slightly different versions of the vaccine for the first and the second dose given 21 days apart. They both target the coronavirus's distinctive spike but use different vectors. The idea is that using two different formulas boosts the immune system even more than using the same version twice and may give longer-lasting protection. Some side effects to the vaccine include a sore arm, tiredness and a mild fever. Hyderabad-based pharmaceutical major Dr Reddy's Laboratories will be importing the first batch of 125 million doses to India during this quarter.
Which countries are signing up for India's vaccines?
India has shipped 64 million doses of vaccines to 86 countries in Latin America, the Caribbean, Asia and Africa. The recipient countries include UK, Canada, Brazil and Mexico. Both Covishield and Covaxin have been exported some in the form of gifts, others in line with commercial agreements signed between the vaccine makers and the recipient nations, and the rest under the Covax scheme, which is led by the World Health Organization (WHO) and hopes to deliver more than two billion doses to people in 190 countries in less than a year. However, in March, India placed a temporary hold on all exports of the Oxford-AstraZeneca vaccine.
VACCINE REGISTRATION
Online registration and appointment can be done through Co-WIN portal
Basic information and details of the photo identification card is required to be registered online.
From one mobile phone number, one can register for four people; however, each person will need their own photo identification document.
If Aadhar card is used as identification document, consent will be obtained and recorded.
Through the portal, one can find out the list of available centres, dates and time of available vaccination slots, to book an appointment as per their choice.
For all Private Hospitals, prior registration and appointment will be the only method of registration.
For Government hospitals, a proportion of slots is available for online registration and appointment; the rest will be kept for onsite registration and vaccination. The walk-in option is available for people above the age of 45 only.
The vaccine is supplied to various parts of India as per availability and distribution plan, beneficiaries load , hence at present the option of choice of vaccine is not available
Appointments for any date for a Vaccination Centre will be closed at 12:00 pm on the day prior to the date.
Those who cannot get themselves registered online can contact their local Government health workers, who will help the beneficiaries to the Government Centre for on the spot registration, appointment, verification and vaccination on the same day.
It is advisable to wait for 2-3 weeks after recovery from COVID symptoms before getting the vaccine.
Adequate immune response takes 2-3 weeks after completion of entire vaccination schedule i.e., after the second dose of Covishield and Covaxin, so it is necessary to get both the doses of the same vaccine.
Vaccination is the only way to protect yourself and your family from the COVID 19 virus. So do your part and get vaccinated at the earliest!
AUTHOR:
SHARANYA D
PROJECT EXECUTIVE
MEDCUORE MEDICAL SOLUTIONS PVT LTD.
REFERENCES:
17. https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-use-authorization-vaccines-explained
18. https://www.mohfw.gov.in/covid_vaccination/vaccination/faqs.html#vaccine-registration