COVID Vaccine: A RAY OF HOPE

Emergency Department in General Hospital, Thrissur, Kerala with symptoms of dry cough and sore throat. She had travelled from Wuhan city to Kerala. Since then the number of COVID-19 cases in India has steadily risen. As of 21 January 2021, the statistics for India were as follows:

The year 2020 which began on a bonhomie note completely derailed as the world slowly fell victim to the COVID-19 virus. From China the virus spread to Europe, the Middle East and the rest of the world.

The first confirmed case of the virus in India was reported  on 27th January 2020. A 20 year old lady was admitted to the Total cases:   1,06,11,719

Total deaths: 1,52,906

Total recovered:  1,02,65,706

Active cases: 1,93,107

Serious critical: 8,944

Total tests conducted: 18,93,47,782

Source:https://www.worldometers.info/

coronavirus/#countries

Vaccine to the rescue

Since the advent of this virus, researchers, scientists and pharmaceutical companies have been in the race to develop a vaccine affording immunity from COVID-19. This brings us to the question - how would a vaccine be able to provide immunity? We can understand this by looking at the basic structure of the COVID-19 virus.

As seen in the image, the virus has a very simple design. Early on, researchers and scientists realised that the simple action of washing hands with soap and water had the ability to destroy the virus. This is because the ingredients in the soap wedge themselves into the outer coating (lipid membrane) and pry it apart. They break the protective covering leaving the inner nucleocapsidprotein vulnerable to destruction.

Tiii date, all vaccines (whether they are to counter MMR, BCG, Chickenpox, Polio) have worked on the simple premise that:

Any pathogen (bacterium/virus/parasite/ fungus) which enters the body causes disease within the body.

•      Every pathogen has sub-parts, unique to it, which form antigens.

•      In a healthy individual, the immune system creates antibodies to seek and destroy these antigens.

•      But learning to defeat a new enemy takes time and during this interval, the individual falls ill.

•     In time, the body produces antibodies to defeat the antigen. It also creates antibody-producing memory cells. These unique cells linger on after the antigen has been destroyed. This is the

body's way to remember how to destroy the antigens if the illness recurs. The second time around, the antibody response is quicker and far more effective. This is because the memory cells have the know-how to start pumping out antibodies to defeat the antigens.

Vaccines contain non-dangerous or inactive parts of the antigen that trigger our immune system to respond. Vaccines protect against disease as they carry either the weakened antigen or the actual blueprints of the antigens. This is immensely helpful, as without falling prey to the disease, the body is able to produce specific antibodies to destroy the antigen and defeat the disease. Immunising enough people, about 60 per cent of the country's population, prevents the virus from causing an outbreak. This concept is known as herd immunity.

Designer vaccines

The prior-mentioned  process sounds straight forward. But the reality is that vaccine development is a lengthy process invoMng numerous man-hours, extensive research and rigorous testing before vaccines can be introduced to the general public. Many state and non-state entities from the public and private sectors need to collaborate in order to successfully create disease defeating vaccines.

All vaccines undergo screenings and assessments to identify the antigen which will activate an immune response. If the vaccine triggers an immune response in animals, it is then tested in human clinical trials in three phases.

While being evaluated, every vaccine undergoes six stages of review -

Pre-clinical testing stage

This phase is done without any testing on humans. An experimental vaccine is first tested in mice or monkeys to evaluate if an immune response is generated, if it is safe and if it has the potential to prevent disease.

Phase 1 safety trials

The vaccine is given to a small number of volunteers to assess its safety, confirm that it generates an immune response and to determine the right dosage.Young, healthy adult volunteers are selected to receive the vaccine in this phase.

Phase 2 expanded trials

The vaccine is administered to several hundred volunteers including healthy adults; children and the elderly to determine if different populations respond differently to the vaccine. There are usually multiple trials in this phase. A placebo group (that is given a comparator vaccine and not the actual vaccine) is also included in phase. This group and the vaccinated group are compared with each other to comprehend whether the changes in the vaccinated group are due to the vaccine or have happened  by chance.

Phase 3 efficacy trials

In this phase, the vaccine is administered to thousands of volunteers in various cities and towns across multiple countries.This phase also has two groups those who receive the actual vaccine and those who receive the comparator vaccine or placebo. The effectiveness of the actual vaccine is judged by comparing how both groups are protected against the disease. The efficacy rate of the vaccine is measured during this phase.Possible rare side-effects of the vaccine are usually discovered during this phase.This phase of trial is mainly to ensure that the findings of the vaccine performance apply to many different populations.

Emergency or limited authorisation

Emergency or limited authorisation to vaccines is approved by countries based on preliminary evidence that they are safe and effective.

Approval

Prior to approval of the vaccine, efficacy and safety is reviewed by the country's regulatory authority.Data is minutely reviewed and the vaccine must be deemed safe and effective across a broad population before it will be approved.

Combined phases

Phases 1 and 2 or 2 and 3 are often combined to fast track vaccine development. This was seen during the making of the COVID-19 vaccine.

Vaccine ingredients

All vaccines contain components which serve a specific purpose. They are:

Antigen

All vaccines contain an active component (the antigen) which generates an immune response, or the blueprint for making the active component.

Preservatives

Preservatives prevent the vaccine from becoming contaminated once the vial has been opened, if it will be used for vaccinating more than one person.

Stabilisers

Stabilisers prevent chemical reactions from occurring within the vaccine and keep the vaccine components from sticking to the vaccine vial.

Surfadants

Surfactants keep all the ingredients in the vaccine blended together. They prevent lumps being formed in the liquid form of the vaccine.

Residuals

Residuals are tiny amounts of various substances used  during manufacturing  or production of vaccines that are not active ingredients in the completed vaccine.

Diluent

Diluent is a liquid used to dilute a vaccine to the correct concentration immediately prior to use.

Adiuvant

Adjuvant improves the immune response to the vaccine, sometimes by keeping the vaccine at the injection site for a little

longer or by stimulating local immune cells.

Different approaches to the COVID-19 vaccine

Researchers and scientists are creating vaccines that target the spike proteins which cover the virus and help it invade human cells. The immune system can develop antibodies that latch onto spike proteins and stop the virus. A successful COVID-19 vaccine will instruct the body's immune system to make antibodies without causing disease. The most common types of approaches include:

DNA vaccines

DNA vaccines contain an engineered DNA which is delivered into the cells. The cells read the viral gene, make a copy in a molecule called messenger RNA (mRNA), and then use the mRNA to assemble viral proteins.The immune system detects the proteins and mounts a defence.

RNA vaccines

RNA vaccines are genetic vaccines that deliver one or more of the coronavirus's own genes into our cells to provoke an immune response. These vaccines deliver messenger RNA into the cells. The cells read the mRNA and make antibodies that provoke an immune response.

Viral vedor vaccines

Viral vector vaccines contain viruses engineered to carry the coronavirus genes. Some viral vector vaccines enter cells and cause them to make viral proteins. Other viral vectors slowly replicate, carrying coronavirus proteins on their surface.

Coming into contact with these proteins causes the body to develop antibodies and launch an attack.

lnadivated or attenuated coronavirus vaccines

Inactivated or attenuated coronavirus vaccines are created from weakened coronaviruses or coronaviruses that have been killed with chemicals. These vaccines incorporate an inactivated or weakened form of a virus that is not able to cause disease. When immune cells encounter them, they make antibodies.

Protein-based vaccines

Protein-based vaccines contain coronavirus proteins but no genetic material. Some vaccines contain whole proteins and some contain fragments of them. Some pack many of these molecules on nanoparticles. These proteins trigger the immune system to make antibodies.

 En garde coronavirus

By mid-December 2020, 57 vaccine candidates were under clinical research. Of these, 40 were in Phase 1-2 trials and 17 in Phase 2-3 trials. In Phase 3 trials, several COVID-19 vaccines demonstrated efficacy as high as 95 per cent in preventing COVID-19 infection.

At present, six vaccines have been approved for public use world-wide:

•     Two mRNA vaccines (Tozinameran from Pfizer-BioNTech and mRNA-1273 from Moderna)

•     Two viral vector vaccines (Sputnik V from the Gamaleya Research  Institute and AZD 1222 from the University of Oxford and AstraZeneca)

•     Two conventional inactivated vaccines (BBlBP-CorV from Sinopharm and CoronaVac from Sinovac)

 Tozinameran from Pfizer-BioNTech

This vaccine contains a blueprint to create a coronavirus protein referred to as spike protein. When injected, it causes cells to

make the spike proteins. These are released into the body and provoke a response from the immune system. Clinical trials showed that volunteers produced antibodies against COVID as well as immune cells called

T-cells that counter the virus.

Tozinameran protected volunteers after the first dosage was injected. The second dose (three weeks later) further boosted immunity. The vaccine efficacy did not vary in people of different races. The vaccine was successful in protecting people with

pre-existing conditions like obesity or Diabetes.People over 65 were as protected as younger adults.

The vaccine received emergency authorisation in USA, UK, Argentina, Chile, Costa Rica, Ecuador, Kuwait, Mexico, Panama, Singapore and the European Union. Bahrain, Canada, Saudi Arabia and Switzerland have approved the vaccine. The Pfizer vaccine is the first to be approved by both the World Health Organization and the US Food and Drug Agency. Pfizer has set a target of delivering 1.3 billion vaccines doses in 2021.

mRNA-1273 from Moderna­ NationaI Institute of Health

This vaccine introduces genetic material (mRNA) upon inoculation. When these genetic instructions, that encode the viral protein, are injected into the upper arm the muscle cells translate them to make the viral protein directly in the body. This gives the immune system a blueprint of what the

real virus looks like without causing disease. This blueprint gives the immune system time to design powerful antibodies that can destroy the real virus in case of a future infection. mRNA vaccines eliminate much

of the manufacturing process because rather than having viral proteins injected, the human body uses the instructions to manufacture the viral proteins itself.

Modema has found that after three months the phase 3 participants still have a strong immune defence against COVID.On 2nd December, Moderna registered a trial to test the vaccine on adolescents between 12 and 18 years of age.

The most important difficulty during development, transport and storage of mRNA vaccines is that they have to be constantly kept below freezing temperatures. mRNA vaccines tend to be unstable and break apart above freezing temperatures.

This vaccine was funded by the US government and the Moderna vaccine is the second vaccine to be authorised by the US Food and Drug Agency. The vaccine received emergency authorisation in US, European Union and Canada. Japan, Qatar and South Korea have sought to purchase the Moderna vaccine. Moderna hopes to produce 500 million to 1billion vaccine in 2021.

Sputnik V from the Gamaleya National Center of Epidemiology & Microbiology and the Russian Dired Investment Fund

This vaccine is a combination of two adenoviruses called Ad5 and Ad26. By combining them, the Russian researchers hoped to prevent the immune system from attacking the vaccine. The immune system learns that the vaccine, though a foreign object, should not be destroyed.

Phase 3 trials showed that this vaccine successfully created antibodies to fight COVID-19 and improved cellular immune response with mild side-effects. Not a single participant of the clinical trials got infected with COVID-19 after being administered

with the vaccine.Sputnik V also was found to have an efficacy of over 90 per cent in people over 60. The dry form of the vaccine can be stored at 2-8 °C, making transportation relatively easier.

The Russian Direct Investment Fund announced  the second interim  analysis of clinical trial which showed 91.4 per cent efficacy for the vaccine on day 28 after the first dose and over 95 per cent efficacy

42 days after the first dose.

Sputnik V website states that 'the vaccine is named  after the first Soviet space satellite. The launch of Sputnik-1 in  1957 reinvigorated  space research  around  the world. The vaccine is therefore called Sputnik V.

The Russian Ambassador to India, Nikolay Kudashev, announced  on 21st December that Russia is working with India to jointly produce  Sputnik V coronavirus vaccine  at Dr Reddy's Laboratories for use in India, Russia and other countries.  India's Hetero Biopharma  has also announced  a deal with the Russian Direct Investment Fund to make more than  100 million  doses of Sputnik V. In all, India will produce about 300 million doses of Sputnik V in 2021.

British drug-maker AstraZeneca has decided to test combining its own

COVID-19 vaccine AZD1222 with Russia's Sputnik. The idea behind this merging of vaccines is to start trials next year using combinations of different kinds of vaccine for the initial and booster vaccinations, in the hope that a mix-and-match approach might maximise the immune response.

Trials are expected to begin in 2021 for a combination AZD 1222-Sputnik V vaccine.

The Sputnik V vaccine received  emergency authorisation  in Russia, Belarus and Argentina. Brazil, Mexico, India and Venezuela  have sought to purchase  the Sputnik V vaccine.

AZD1222 from the University of Oxford and AstraZeneca

This vaccine is called Covishield in India. This vaccine was designed by genetically engineering an adenovirus that normally infects chimpanzees. When researchers gave the vaccine to monkeys, they found that it protected the animals from COVID-19.

Phase 2/3 combined trials looked at how people aged 18 to 70 years and older responded to the vaccine.  In September 2020, AstraZeneca had halted global trials after a trial participant developed transverse myelitis (inflammation of both sides of one section of the spinal cord). Within a week, the trials restarted suggesting that the particular participant had received a placebo. No serious side effects were detected at any age. The older volunteers produced about as many antibodies against the coronavirus as the younger ones.

During these trails, due to human error (incorrect measurement of the vaccine), the volunteers all got two doses, but in some cases the first dose was only half strength. Even at half strength, the dose led to 90 per cent efficacy while two standard-dose shots led only to 62 per cent efficacy. The researchers hypothesised that the lower first dose mimicked the infection perfectly and this led to the higher efficacy rate. This, however, raised questions about the preliminary results as the half dose was administered only to people less than

55 years of age. Eventually the trail data showed that the vaccine had an efficacy rate and was complete protection against severe COVID-19 symptoms.

There were three cases of transverse myelitis (a form of paralysis) after people were inoculated in the trials. One happened

in the placebo group and one in the control group. A third case in the vaccine group was deemed due to pre-existing multiple sclerosis, a form of nerve damage.

Committees of experts have assessed the data and found that the vaccine could be considered as generally safe; and transverse myelitis was unrelated to the vaccination.

The vaccine received emergency authorisation in UK and India. The European Union and South Africa have sought to purchase the AZD1222 vaccine.

Serum Institute of India has already manufactured 50 million doses of this vaccine and can make 1000 million more by March 2020. Serum Institute of India expects Covishield to be available to the general Indian public in 2021. The first 100 million doses of Covishield vaccine will be sold to the Indian government at Rs 200 per dose, after which prices would be higher. The vaccine is expected to be sold in the private market at Rs 1,000 per dose. The vaccine's economy, early storability and transport via simple refrigeration makes it suitable for developing countries like India. BBIBP-CorV from the Beiiing Institute of Biological Products and Sinopharm

This vaccine works by teaching the immune system to make antibodies against

COVID-19. The antibodies attach to viral proteins (spike proteins) on the surface of the virus. The researchers inactivated the COVID-19 virus so it could no longer replicate but its spike proteins remained intact. The researchers then mixed the inactivated viruses with an adjuvant (adjuvants stimulate the immune system to boost its response to a vaccine). The inactivated COVID-19 virus is destroyed by antibodies that stick to the virus and prevent the virus from entering healthy cells.

The Beijing Institute of Biological Products created an inactivated coronavirus vaccine that was put into clinical trials by the

state-owned Chinese company Sinopharm. Beijing Institute researchers reported that the vaccine produced promising results in monkeys. Phase 1/2 combined trial showed that the vaccine didn't cause any serious side effects and enabled people to make antibodies against coronavirus.

Though Sinopharm announced that the vaccine had efficacy of 76.34 per cent, the Ministry of Health and Prevention, U.A.E. announced it had an efficacy rate of

86 per cent. 1111 date, Sinopharm has not commented on this discrepancy.

The vaccine received emergency authorisation in China, U.A.E and Bahrain. The European Union has sought to purchase the Sinopharm vaccine. China plans to vaccinate 50 million people using this vaccine by mid-February.

CoronaVac from Sinovac

Sinovac Biotech, a private Chinese company, developed an inactivated vaccine called CoronaVac. Phase 1/2 trials found no severe adverse effects and produced an immune response. Efficacy data from phase 3 trial is unknown, at the time of this magazine going to print, as the phase 3 trial findings are yet to be published.

Sinovac has said that this vaccine has an efficacy rate of over 50 per cent. It is to be administered in two doses, given two weeks apart. It is a muscle injection which can be stored at refrigeration temperature.

Sinovac said it has manufactured

300 million doses in 2020 and will increase their vaccine production to 600 million doses in 2021. The vaccine received emergency authorisation in China. It was administered to people in relatively high-risk jobs in the eastern Chinese city of Jiaxing. Indonesia and Ukraine have sought to purchase the CoronaVac vaccine.

The Desi vaccine

Covaxin, being developed by Bharat Biotech, the Government-run  Indian Council of Medical Research and the National Institute of Virology, is considered to be India's first indigenous COVID-19 vaccine. Covaxin is an inactivated vaccine. It introduces a part of the novel coronavirus, instead of the whole,  into the

human body to provoke the sort of immune response that the body will remember.

When in future, the immune system faces the actual novel coronavirus infection, it will know what to do to flush the virus out of the body and end the infection.

The Indian Council of Medical Research provided the virus-isolate to Bharat Biotech in May 2020. The company cultured the virus at its facility, purified and chemically inactivated  it to obtain the candidate known as Covaxin. Bharat Biotech ran a combined phase 1/2 trials of Covaxin to test its safety and capacity to stimulate immune responses against the virus. Currently in its Phase 3 clinical trial, the vaccine could to be launched as early as February 2021 as last-stage trials began in November 2020. Efficacy data from phase 3 trial is unknown, at the time of this magazine going to print, as the phase 3 trial is still on-going.

Bharat Biotech estimates its efficacy to be 60 per cent. Covaxin has been designed to be efficacious based on receipt of

two-doses, given 28-days apart. Bharat Biotech has also clarified that the vaccine efficacy will be determined 14-days after the second dose. Covaxin can be stored at least a week at room temperature

 Approval by Indian authorities

The Subject Expert Committee JOUR NEY OF A VACCINE - THE 'COLD CHAIN'(SEC)oftheCentralDrugsStandardControlOrganisation(COSCO),India'sdrugregulator,meton1stJanuary2021toreviewtheemergencyuseauthorisationforSerumInstituteofIndia (Sii)andBharatBiotechCovishieldandCovaxinvaccinesrespectively.

Subsequently, the Oxford-AstraZeneca - Sii Covishield vaccine received a nod from the SEC for emergency  authorisation use. Covaxin received emergency use authorisation for clinical trial mode where all vaccine recipients will be tracked and monitored as if they are in a trial.

Distribution and delivery

Serum Institute of India (Sii) has stockpiled 75 million doses of AstraZeneca-Oxford University COVID vaccine and will be increasing it to 100 million doses by the frrst week of January. In his statement, Mr Adar Poonawalla, the CEO of Serum Institute, said "50 per cent of the vaccine supplies would go to India and the rest would go to COVAA, a consortium of 190 world governments formed to ensure free and fair distribution of COVID-19 vaccine around the world.

However, during the initial months, India would prioritise supplies".

The Indian government is planning to vaccinate 300 million people in the first wave of vaccinations. The frrst phase will target 10 million frontline health workers by February 2021. In the second phase,

20 million frontline and essential workers would be administered the jab by March 2021 and in the third phase, 270 million people aged over 50 and with co-morbidities would be vaccinated by August 2021.

Registration for the vaccine

The Government of India has set up an official app called CoWIN (COVID-19 Vaccine Intelligence Network) app.

The Ministry of Health and Family Welfare website states, 'The app has four modules - user administrator module, beneficiary registration, vaccination and beneficiaiy acknowledgment, and status updation. The CoWIN app or website will give three options for registration including

self-registration, individual registration, and bulk  upload.

For self or individual registrations, users will have to upload their photo identity to register on the app. This could be an aadhaar card, driving license, Health Insurance Smart Card issued under the scheme of Ministry of Labour, MNREGA job card, PAN card, passbook  issued by banlq' post office,  passport,  pension  document, service ID card issued to employees by CentraVState Govt./PSUs/ Public Limited Companies, smart card  issued  by RGI under NPR and voter ID.

Demographic details like name, date of birth, permanent and current address and details of co-morbidities if any will need to be provided. There will be no on the spot registration.

 Vaccination drive

As per the operational guidelines drafted by the Centre and issued to states and union territories:

Every vaccination centre will have three rooms - waiting room/ area, vaccination room and an observation room.

Vaccinations will occur between 9 am to 5 pm. Each centre will be manned by:

Vaccination officer 1will pre-check registration status and verify photo ID prior to the person entering the waiting area. (They will mostly be police, home guard, civil defence, NCC, NSS, NYK)

Vaccinator officer 2 will be in charge of vaccinating people. They will be doctors (MBBS/BDS), staff nurse, pharmacist, auxiliary nurse midwife, lady health assistant- anyone legally authorised to administer an injection - may be considered as potential vaccination officer.

Vaccination Officer 3 will verify the ID document in the CoWIN system after vaccination of the beneficiary. Then, the vaccination officer 3 will tick the vaccination completion checkbox in CoWIN system.

The vaccine receiver will receive the SMS notification with a link for the date and time of subsequent dose.

Vaccination officers 3 and 4 will be in charge of ensuring people wait up to 30 minutes after receiving the vaccine.

They will monitor people for any adverse event following immunisation.

The guidelines also state that a multi-department  effort will be necessary. Some examples provided  include - the department  of power  supply must ensure unhindered supply of electricity, the state AIDS control society will ensure hesitancy is taken  care of. The animal husbandry department would support provision  of dedicated  cold  storage  equipment  and facilities, if required. The department of food and civil supplies would be supporting provision  of cold storage spaces and transport system, if needed. There would be biometric  authentication  at session  sites.

Defence forces would be involved in support registration  of armed forces'

beneficiaries and supply for vaccine delivery in hard to reach and security sensitive At present,  though  the Pfizer and Moderna vaccines have higher efficacy, in terms of affordability, accessibility, storage  and  transport,  the AstraZeneca-Oxford-Sil vaccine  is more suitable for more inoculations at scale. The deviation from the 0 to 28th day dose is probably 0 to 90th day dose, while deviating from evidence,  is rooted in pragmatism  and reach. This aspect  requires  further  debate.India plans to receive and utilise millions doses of vaccines against the disease  and immunise up to 300 million people by August 2021. A dry run for COVID vaccination  was conducted  by all states and union territories on 2nd and 8thJanuary 2021 to test the delivery systems required  to inoculate millions of people starting  January. The Ministry of Health and Family Welfare has also released  a document to address misgivings  about the vaccine  as well as any vaccine hesitancy felt by Indians. This document acknowledges the role of key influencers in spreading correct information and ensuring vaccine compliance.

Please Note: Diabetes Health recommends readers to dial the state helpline no - 104 - for up-to-date information and guidance on Covid-19 vaccination.