Why you should not miss antibody cocktail?

Hello everyone. Have you ever taken a cocktail?

No! Do you want to?

Well, I have new type of cocktail for you. You may have heard about it. It is an antibody cocktail. Sounds weird, isn’t it? So, let’s have a deep discussion on the very topic. After reading this, you will have complete idea about-

  • What it is?
  • Who created it?
  • What does it contain?
  • Who can take it?
  • Who are high risk patients?
  • Is it worthwhile to get administered?

So, let’s gear up for the 1st question.

What is it?

To able to answer to this, look into the combined words- ‘Antibody’ and ‘Cocktail’. Antibody(Ab)- These are the proteins that fight pathogens such as bacteria and viruses by recognising immune system triggering molecule i.e. antigen. These are also known as by Immunoglobulins, Ig. There are main 5 isotypes- IgM, IgE, IgG, IgA, IgD. These are produced by plasma cells, which are differentiated B lymphoctyes. To know more, click here.

Cocktail- It is a drink formed by combinations of different spirits or spirits with fruit juice or creams.

Therefore antibody cocktail means- ‘A mixture which is formed by two antibodies.’

Here, we will focus on REGN-COV2.

Who created REGN-COV2?

It is created by Regeneron (an American biotechnology company based in New York) with collaboration with Roche (a Swiss multinational pharmaceutical company) for distribution across the globe.

Regeneron will conduct the manufacturing and distribution in US and Roche will be responsible for distribution outside US.  Roche India and Cipla limited brought the first batch of antibody cocktail in India in May, 2021.

How is it created?

To answer this, we need to know about:

VelociSuite:

  • These are technologies that include VelociGene and VelocImmune that are used to produce new drugs.

VelociGene:

  • These are technologies that enable precisely manipulation of mouse genome very rapidly.
  • It is performed to create animals (mice) expressing human diseases. The mouse is known as by VelociMouse, which are directly created from modified embryonic stem cells to have human immune system.
  • Means, no one needs to perform multiple generations of breed, hence it is very rapid.
Fig. 1

VelocImmune: The technology that gives ability to produce new drugs in a rapid manner. In this, fully human monoclonal antibodies are produced from VelociMouse that are modified with genetically humanized immune system.

The scientists in Regeneron, assess human antibodies produced by VelociMouse that are genetically modified by VelociGene technology to have antibodies from covid recovered patients.

What does it contain?

As stated, they contain two antibodies that are IgG1. These are- Casirivimab (IREGN10933) and Imdevimab (REGN10987), which are potent human monoclonal antibodies created in labs. They strongly and non-competitively bind with virus’s spike protein in 2 different and non-overlapping locations shrinking the chance of viral escape.

Before going ahead, we have to learn about some terms that are somehow related to antibody cocktail.

IgG:

  • These are one of the five main types of immunoglobulins (Ig) present in our body.
  • This is the most abundant Ig in blood that neutralizes bacterial and viral infection. To know more, click here.

Hybridoma

  • These are hybrid cells that are created by fusing two cells. One is monoclonal antibody-producing B lymphocyte and other is a myeloma (A#1) cell for immense growth of hybridoma.

A#1. Myeloma: Or multiple myeloma, is a bone marrow cancer. Its origin is unknown. Though it is associated with males more, with elderly age, in black people and is highly associated with history of myeloma in family.

In this, a kind of white blood cell (WBC) called plasma cell is affected.

Plasma cells are needed to form antibodies. Here, the plasma cells become abnormal and increased in number hence causing many complications.

Symptoms: Could be asymptomatic.

  • Recurrent infections as the antibody production is affected.
  • Fatigue or muscle weakness
  • Weight loss
  • Appetite loss
  • Constipation
  • Nausea or sometimes vomiting

Later on it can lead to:

  • Anemia, as normal blood cells are not formed now.
  • Renal failure
  • Prone to fracture as bones get weakened with the cancer progression

Treatment:

  • Immunotherapy (stimulating immune system)
  • Chemotherapy (cancer killing drugs)
  • Radiotherapy (high energy radiations like X-Ray to kill cancer cells preventgin them from spreading further)
  • Using steroidal drugs such as corticosteroids for pain and inflammation.

Monoclonal antibody:

  • It is an Ig which is made of identical copies made from a single unique B cell that targets a specific antigen.
  • These are used to treat cancers like brain and breast cancer by stimulating immune response that consumes cancer cell membrane arresting their survival.

Q#1: What is the main difference between monoclonal and polyclonal antibodies?

A: It’s on the basis of epitopes. Ponyclonal antibodies bind to different epitopes while monoclonal antibodies bind to only one type of epitope.

Epitopes:

  • Part of antigen where antibody attaches itself.

Spike proteins:

  • These are glycoprotein structure overhanging from virus surface. Also known as Peplomers.
  • It is the main antigenic component of SARS-COV2 by which they attach and cause infection.

Receptor Binding Domain

  • A part of S1 subunit on spike protein from where it binds to host cells, infecting them.

So without further ado, let’s understand the mechanism of action of these two.  

  • Casirivimab and Imdevimab are unmodified in the Fc region (A#2).
  • They both bind non-competitively to the non-overlapping epitopes of spike protein’s receptor binding domain (RBD) at 2 different locations of SARS-CoV2.
  • This prevents the RBD to bind to ACE2 receptor of the host cells which is the receptor for SARS-COV2 virus.
  • Hence, preventing their entry into the cell itself and the progression to severe state in return.

A#2. Fc region: Short of Fragment crystallisable region. It means that the region of antibody that binds with cell surface receptors by amino acid crystallisation. It contains constant region of Heavy chain of antibody.

Other region is Fab region which is antigen-binding region which well… the name is enough to know about its function.

Now, till now we have learned about its basic structure and has gotten idea of its action mechanism. Now, about the people who can take and how.

How is it administered and to whom?

  • These are administered either intravenously (IV) or subcutaneously (SQ) by doctor or professional nurse where they observe for post-administration effects for one hour.
  • SQ administration should be done consecutively at different locations i.e. thigh, back of upper arm and abdomen.
    • Navel region, damaged skin and waistline should be avoided.
  • IV is preferred over SQ.
    • SQ is performed when IV is not practical for any cause and would be a setback in the treatment.

Who can take it?

  • It is especially is to be administered in those adults or pediatric patients ( 12 years or older) who have mild to moderate symptoms
  • These patients are at the high risk of developing severe covid symptoms and have no requirement of oxygen.

Here, you have to remember it is not benefiting those who are already in serious condition and are hospitalised as it could worsen their conditions.

The high risk patients should be the first candidates for the drugs. As considering India, 1st batch arrived in May and 2nd batch in mid June (100K packs).

So, Who are high risk patients?

  • Age >=60 years 
  • Obesity
  • Pregnancy
  • Neurodevelopmental disorders like Cerebral palsy (Brain disorders where person in unable to maintain balance and posture).
  • Cardiovascular disease, including hypertension
  • Chronic lung disease, including asthma 
  • Type 1 or type 2 diabetes mellitus 
  • Chronic kidney disease, including those on dialysis 
  • Chronic liver disease
  • lmmunosuppressed, based on investigator’s assessment.
    • Examples of immunosuppressed includes: Patients gone through cancer treatment, bone marrow or organ transplantation, immune deficiencies like HIV (if poorly controlled or evidence of AIDS), sickle cell anemia, thalassemia or prolonged use of immune-weakening medications.

Isn’t there any side-effect?

There are no side-effects. Well, it would be wishful thinking if I say so. But there are a few to mention. These are hypersensitivity reactions like anaphylaxis (life threatening allergic reactions leading to shock) and infusion-related reactions.

During infusion or in a period of 24 hours after infusion, sometimes adverse reactions have been observed. These are:

  • Fever and chills
  • Difficulty breathing and chest pain
  • Arrhythmia
  • Altered blood pressure
  • Fatigue, weakness and muscle pain
  • Disturbed mental status

If any of these are observed, immediately it should be stopped or supportive care should be provided.

So, why should we take risk of antibody cocktail if there are these many adverse effects?

Is it beneficial?

Yes, it is, and in many ways like:

  • It shortens the symptoms duration by four days.
  • Most of the time covid infected persons have seen improvement in their conditions within 12 hours of the treatment.
  • It effectively reduces the hospitalisation rate to 70% when administered at right time i.e. within 7 days of infection.
  • It’s also found to be treating delta variant and is said to be effective against other variants too.
  • In the trails, in phase III, it was found out that it not only is effective in treating and inhibiting the disease progression but it is also beneficial in prevention of the infection.

What are its dosage and storage instructions?

  • It needs to be stored at temperature range from 2o to 8oC.
  • The antibody cocktail after refrigeration is calmed down to normal room temperature for 20 minutes.
  • If the solution is not administered immediately then can be stayed at room temperature (25oC) for 4 hours or should be put in refrigerator again but not more than for 36 hours.
  • Each pack can be used for 2 patients as it contains 2400 mg of both the antibodies, 1200 mg of each.
  • One patient has to be administered 600 mg of dose from the vials of each antibodies.
  • After administration, patient needs to be monitored at least for one hour.

We have talked about who can take it. But do you know who have taken it? There was one person who made this therapy into spotlight.

I am talking former US president Donald Trump who received this treatment after reported covid positive last year in October. At that time it was in trial stages and even at that time found to be highly effective.

Also, Germany was first EU country to use antibody cocktail.

Why can’t everyone get it?

The economy of the world is already down. And the same problem is here.

Therefore, despite positive results, it won’t be convenient for everyone as even one pack costs around 1,600 USD (1,20,000 in INR) but because it can be used for 2 patients for each pack, it costs 800 USD (60,000 in INR) for each patient. This is not in everyone’s hand to afford.So, it brings to us to the question.

Is it really worthwhile to get administered?

I mean, we already have vaccines. Even more, they are being administered free of cost under central government vaccination program. To understand this, we must know how it is actually different from vaccines in the sense.

  • Unlike vaccines, it provides passive immunity (A#3) hence a quick effect.
  • Unlike vaccines, a single dose is enough where vaccines require 2 dosages with a few weeks gap.
  • Vaccines are administered before the actual infection where antibody cocktail is administered after infection (Antibody cocktail should be administered within 2 to 3 days for best results). So if some unvaccinated person or person despite of vaccination has covid19. This is the approach one can follow.

A#3. Passive immunity: In this, ready-made antibodies fight for infection unlike active immunity where our body creates its own antibody which is the path the vaccine takes. They guide our body to create antibody for a given pathogen

Thus you can think how much of revolutionary it is in development of new treatments towards covid free world.

I hope you have learned something new and it may come useful to you. Let me know your views on it in the comment section.

Later.

Published by signaturedoctor

I am a doctor-to-be pursuing my medical studies. I want to share my knowledge to fellow medical students and to other interested people.

3 thoughts on “Why you should not miss antibody cocktail?

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