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Proposed Vaccines, Treatments in the Context of COVID-19

Coronavirus disease 2019 (COVID-19)

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Vaccines

  • Vaccines prevent or mitigate infections.
  • They are designed to induce a protective immune response in the body against the viruses.
  • When vaccinated, the immune system of the body produces a specific response, consisting of specific T cells & specific antibodies that fight off the infection when exposed to the virus occurs at a later stage.
  • More importantly, vaccination also leads to the induction of a specific immunological memory against the viruses represented in the vaccine.
  • There are about a half-dozen basic types of vaccines, including killed viruses, weakened viruses, & parts of viruses, or viral proteins.
  • All aim to expose the body to components of the virus so specialized blood cells can make antibodies.
  • In the past, it has been difficult to manufacture vaccines for new zoonotic diseases quickly.
  • A lot of trial & error is involved in making a vaccine. Hence it could take years to invent a vaccine.
  • A new approach being taken by Moderna Pharmaceuticals, which recently began clinical trials of a vaccine, is to copy genetic material from a virus & add it to artificial nanoparticles.
  • This makes it possible to create a vaccine based purely on the genetic sequence rather than the virus itself.

Differences between Vaccine & Drugs

Vaccines

Drugs

  • Vaccines are almost always biological products – Subject to widespread variation even between batches.
  • Drugs may be chemical or biological
  • Chemical drugs have remarkable identity between batches & even between manufacturers.
  • All vaccines require special conditions of storage – usually cold storage.
  • Chemical drugs do not usually require cold storage.
  • Some biological drugs may require cold storage e.g. Insulin.
  • Most chemical drugs are administered orally as tablets, capsules, suspensions etc.
  • Vaccines are large molecules usually administered parenterally.
  • Some vaccines may be given orally (e.g. polio vaccines) or intranasally.
  • Some drugs are given through various other routes e.g. IV, IM., SC, dermally etc.
  • Vaccines are normally given in “schedules” which must be adhered to– For whole populations and/or age groups.
  • Use of drugs is individualised.
  • Vaccines are given mostly to PREVENT disease.
  • Drugs are given to treat, diagnose or prevent disease.
  • Vaccines are supposed to protect whole populations (“herd immunity”)
  • Drugs are normally for the benefit of the individual.
  • Examples- Covaxin, ChAdOx1, SputnikV.
  • Examples- Itolizumab, Hydroxychloroquine, Dexamethasone, Remdesivir

Antiviral treatments for COVID-19

Antivirals

  • Antivirals are drugs that can treat people who have already been infected by a virus.
  • They also can be used to prevent or limit infection when given before or shortly after exposure, before illness occurs.
  • A key difference is that the antiviral drug is effective only when administered within a certain time frame before or after exposure & is effective during the time that the drug is being administered.

Antibiotics

  • Antibiotics are medicines that interfere with the reproduction of bacteria & are, therefore, only useful for treating bacterial infections.
  • Viral diseases, like influenza, can therefore not be treated with antibiotics.
  • Inappropriate use of antibiotics contributing to the development of antibiotic resistance.
  • Secondary bacterial infections that may occur in tissues that have been damaged by influenza virus infection may well be treated with antibiotics.
  • Antiviral treatments use various tactics to slow down the virus’s spread, though it is not yet clear how effective any of these are.
  • Chloroquine & hydroxychloroquine, typically used to fight malaria, might inhibit the release of the viral RNA into host cells.
  • Favipiravir, a drug from Japan, could keep viruses from replicating their genomes.
  • Combination therapy of lopinavir & ritonavir, a common HIV treatment that has been successful against MERS, prevents cells from creating viral proteins.
  • Some believe the ACE2 protein that the coronavirus latches onto could be targeted using hypertension drugs.
  • Another promising approach is to take blood serum from people who have recovered from the virus & use it & the antibodies it contains as a drug.
  • It could be useful either to confer a sort of temporary immunity to health-care workers or to combat the virus’s spread in infected people.
  • This approach has worked against other viral diseases in the past, but it remains unclear how effective it is against SARS-CoV-2.

Major Vaccines in News in the context of COVID-19

What is ZyCoV–D?

  • ZyCoV-D is a plasmid DNA vaccine, under the Vaccine Discovery Programme supported by the Department of Biotechnology under the National Biopharma Mission.
  • Plasmids are circular deoxyribonucleic acid (DNA) vectors that can be used as vaccines to prevent various types of diseases.
  • In the pre-clinical phase, the vaccine was found to elicit a strong immune response in multiple animal species like mice, rats, guinea pigs & rabbits.

What is Oxford’s ChAdOx1 Covid–19 vaccine?

  • Vaccine, based on a chimpanzee adenovirus called ChAdOx1, elicited antibody & T-cell immune responses.
  • Oxford’s AZD1222 vaccine is made from a genetically engineered virus that causes the common cold in chimpanzees.

What is COVAXIN?

  • It has been developed by the company Bharat Biotech India (BBIL) in collaboration with ICMR’s National Institute of Virology (NIV).
  • It is an “inactivated” vaccine — one made by using particles of the Covid–19 virus that were killed, making them unable to infect or replicate, ie non replicating.
  • Injecting particular doses of these particles serves to build immunity by helping the body create antibodies against the deadly virus.

What is Non–Replicating Viral Vector?

  • The SARS–CoV–2 virus uses the spike on its surface, the ‘spike protein’, to enter & infect cells & multiply.
  • A non–replicating viral vector vaccine uses a weakened version of a different virus to carry this Covid–19 spike protein into the body, but it is modified not to replicate.

What is the mRNA vaccine?

RNA Vaccine

DNA Vaccine

  • These use messenger RNA (mRNA) molecules that tell cells what protein to build.
  • In this case, the mRNA is coded to tell cells to build the molecular structure on the surface of SARS–Cov–2 — which the immune system will recognise & build antibodies against.
  • These vaccines use genetically engineered DNA molecules that, again, are coded with the antigen against which the immune response is to be built.
  • The genetic blueprint (or code) in living organisms is stored in a double-stranded molecule called DNA (deoxyribonucleic acid), which makes proteins that are responsible for nearly every function in the human body.
  • The conversion of DNA code into proteins requires a single-stranded molecule called the mRNA (messenger ribonucleic acid).
  • In an analogy with computers, one may think of the DNA as the hardware, the mRNA as the software & proteins as the applications.
  • The mRNA-1273 is a piece of RNA that carries the code to make the COVID-19 virus Spike protein when introduced into cells.
  • This protein present on the virus surface is critical for its entry into cells. Immunity (antibodies) to the Spike protein can block virus entry & its multiplication, & thus ameliorate the disease.

Sputnik-V

  • This vaccine has been developed by Moscow’s Gamaleya Institute in collaboration with Russia’s defence ministry.
  • The vaccine is based on the DNA of a SARS-CoV-2 type adenovirus, a common cold virus.
  • In this vaccine, adenovirus is used as a tool to deliver genes or vaccine antigens to the target host tissue.
  • The vaccine uses the weakened virus to deliver small parts of a pathogen & stimulate an immune response.
  • The vaccine is administered in two doses & consists of two types of human adenovirus, each carrying an S-antigen of the new coronavirus, which enter human cells & produce an immune response.

Which is the Best Vaccine Suited for India?

  • Comparing the top three vaccines based on:

Efficacy Rates

COVID-19 VaccinesCovishield vs Covaxin

Pricing

  • Pfizer’s candidate is the steepest one right now, costing $20 per dose.
  • Moderna’s make comes up to cost somewhere around $15-$17 per dose.
  • Oxford-Astrazeneca’ shot is by far the cheapest vaccine under offering, as little as $5- $6 (Rs.1000).

Side Effects

  • Both Moderna & Pfizer-BionTech haven’t reported the occurrence of undue or alarming side-effects.
  • Neither have reports of adverse reactions emerged from people who have been vaccinated right now.
  • In comparison to this, the Oxford-Astrazeneca vaccine has been surrounded by controversies in the past months with the many ‘strange’ side-effects being reported from volunteers

Storage & shelf-life

  • Storage & shelf-life are prime factors that determine how effective a vaccine would be in real-world settings.
  • Many experts claimed that Pfizer’s vaccine model will not be well-suited for developing nations, since it requires extreme temperature settings to be stored in & additional shipping ingredients.
  • The vaccine can be stored for use for up to 5 days’ time in a regular refrigerator, for 30 days in a dry-ice freezer, or 6 months’ time in ultra-cold freezers, which are not feasible to arrange everywhere.
  • Moderna faces similar challenges but is slightly less expensive to ship & can stay stable for a longer time, as compared to Pfizer.
  • Oxford’s dose, wins since it is a vaccine prepared using traditional settings, can be stored for use for longer months, easily delivered & administered.

Important Drugs in News in the context of COVID-19

What is Itolizumab?

  • This was used for treating chronic plaque psoriasis.
  • Plaque psoriasis is a chronic autoimmune condition in which skin cells build up & form scales & itchy, dry patches.
  • It can also be used in the treatment of CRS in moderate to ARDS in severely affected patients of the corona.
  • CRS (cytokine release syndrome) & ARDS (acute respiratory distress syndrome) happen due to COVID–19 suffering.
  • CSS is an uncontrolled attempt by the immune system to neutralise the virus that often ends up damaging the lungs & other organs & even death.
  • ARDS is a disease in which the lung loses its capacity to expand further.
  • Biocon’s biomanufacturing facility which is located at Biocon Park in Bengaluru will be manufacturing & formulating Itolizumab as an intravenous injection.
  • Biocon has licensed Itolizumab from Cuba twenty years ago & this is an original innovative Indian drug.

What is Hydroxychloroquine?

  • It is a drug used in the treatment of autoimmune diseases such as rheumatoid arthritis & lupus.
  • Hydroxychloroquine (HCQ) is also used for the prevention of malaria & its treatment; it is a derivative of the antimalarial drug chloroquine.
  • Hydroxychloroquine can only be used in places where chloroquine is still effective.
  • There are only a few places left in the world where hydroxychloroquine is still effective including parts of Central America & the Caribbean.
Hydroxychloroquine: Why is it so much in the spotlight?
  • The prime mover of the theory that HCQ works against Covid–19 has been President Trump, starting with his tweet in March: “HYDROXYCHLOROQUINE & AZITHROMYCIN (antibiotic), taken together, have a real chance to be one of the biggest game-changers in the history of medicine.

What is Dexamethasone?

  • Dexamethasone reduces the production of the chemicals that cause inflammation & also reduces the activity of the immune system by affecting the way white blood cells function.
  • Dexamethasone falls in a category called corticosteroids, which closely mimic cortisol, the hormone naturally produced by the adrenal glands in humans.
  • It is commonly used in treatment for rheumatological inflammatory conditions: inflammations of muscles, inflammation of blood vessels, chronic arthritis, & lupus.
  • It is used in lung diseases, kidney inflammation & eye inflammation, & to reduce swelling associated with tumours of the brain & spine.
  • In cancer patients, it is used to treat nausea & vomiting caused by chemotherapy drugs.

How Useful is it in Covid–19 Treatment?

  • During the SARS outbreak in 2003, corticosteroid therapy was used to reduce inflammatory–induced lung injury.
  • In Covid–19, too, many countries are investigating the effectiveness of corticosteroid therapy on patients with an acute respiratory infection.
  • Also, the World Health Organization (WHO) has prioritised the evaluation of corticosteroids in clinical trials to assess safety & efficacy.

What is Remdesivir?

  • Its an antiviral drug being used to treat COVID–19 patients.
  • Remdesivir is designed to obstruct the stage of replication, when the virus creates copies of itself, followed endlessly by the copies creating copies of themselves.
  • Polymerase enzyme is targeted by remdesivir

How does replication take place?

  • Once the virus enters the human cell, it releases its genetic material, which is then copied using the body’s existing mechanism.
  • At the replication stage, the key viral protein at play is an enzyme called RdRp (an enzyme is a kind of protein that speeds up chemical reactions within a cell).
  • It is RdRp that makes the copies, by processing components of the RNA of the virus.
  • In scientific literature, such an enzyme is called a polymerase (the p is RdRp stands for polymerase) or a replica. In any case, this is the enzyme that is targeted by remdesivir.

How exactly does remdesivir target this enzyme?

  • In order to replicate, the copy machine processes raw material from the virus RNA, broken down by another enzyme with that specific function.
  • When a patient is given remdesivir — the inhibitor — it mimics some of this material, & gets incorporated in the replication site.
  • With remdesivir replacing the material it needs, the virus fails to replicate further.
How far has this action been established?
  • The drug itself was designed to act against the Ebola virus, which is not a coronavirus.

Favipiravir

  • Favipiravir is an antiviral given to inhibit viral replication.
  • It is used as an anti-influenza drug.
  • It is being used for moderately symptomatic to severely ill Covid patients, but access is not easy.

Plasma Therapy

What is Plasma?

  • Plasma is the almost–clear liquid left behind after RBCs; WBCs & platelets are removed from the blood.
  • Plasma fluid carries the blood components throughout the body.

    Link– Source & Credits

  • Plasma is the largest part of your blood. It makes up more than half (about 55%) of its overall content.
  • When separated from the rest of the blood, plasma is a light–yellow liquid.
  • Plasma carries water, salts & enzymes.
  • The main role of plasma is to take nutrients, hormones, & proteins to the parts of the body that need it.
  • Cells also put their waste products into the plasma.
  • The plasma then helps remove this waste from the body.

What is Convalescent Plasma Therapy?

  • Convalescent plasma therapy is an experimental treatment that some doctors are using for people with severe coronavirus disease in 2019 (COVID–19).
  • People who’ve recovered from COVID–19 have antibodies — proteins the body uses to fight off infections — to the disease in their blood.
  • The blood from people who’ve recovered is called convalescent plasma.
  • Researchers hope that convalescent plasma can be given to people with severe COVID–19 to boost their ability to fight the virus.
  • It also might help keep people who are moderately ill from becoming more ill & experiencing COVID–19 complications.

    Link– Source & Credits

Plasma vs Serum

  • Serum is plasma minus the clotting factors & blood cells.
  • While removing the clotting factors (by centrifugation), the protein fibrinogen is converted to fibrin.
  • Fibrin is an insoluble protein that is used to assist in the repair of tissue damage by forming a clot.
  • A key difference between plasma & serum is that plasma is liquid, & serum is fluid.
  • Plasma contains fibrinogen which is absent in serum.
  • Both plasma & serum can be extracted from blood but it’s worth noting that serum is obtained after the clotting of blood, while plasma can be obtained before the coagulation of the blood.
  • Serum is mostly used for blood typing but is also used for diagnostic testing.
  • Plasma, on the other hand, is mostly used for blood-clotting related problems.

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