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 is it?
- Who created it?
- What does it contain?
- Who can take it?
- Who are high risk patients?
- Is it really worthwhile to get administered?
So, let’s gear up for the 1st question.
What is it?
To able to answer this, look into both of the terms in its name- ‘Antibody’ and ‘Cocktail’.
Antibody(Ab)- These are the proteins that fight pathogens, bacteria and viruses by recognising immune system triggering molecule i.e. antigen. These are also known as by Immunoglobulins, Ig. There are few isotypes- IgM, IgE, IgG, IgA, IgD. These are produced by plasma cells, which are differentiated B lymphoctyes.
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, for ex.- 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) the distribution will be carried out worldwide. Regeneron will conduct the manufacturing and distribution in US and Roche will be responsible for distribution outside US. Eg- 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 enables precisely manipulation of mouse genome very rapidly. It is performed to create animals(mice) expressing human diseases. The mouse are 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.
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 Abs that are IgG1. These are- Casirivimab(IREGN10933)and Imdevimab(REGN10987), which are potent human mAbs(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, let us know about some terms that are somehow related to antibody cocktail.
IgG- These are one of the five main types of immunoglobulins present in our body. This is the most abundant Ab in blood that neutralizes bacterial and viral infection.
Hybridoma- These are hybrid cells that are created by fusing 2 cells. One is monoclonal Ab-producing B lymphocyte and other is a myeloma(cancer of immune system) cell for immense growth of hybridoma.
Monoclonal antibody(mAb)- It is an Ab which are 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.
Question for you: What is the main difference between mAbs and polyclonal antibodies?
Ans: It’s on the basis of epitopes. pAbs bind to different epitopes while mAbs bind to only one type of epitope.
Epitopes- Part of antigen where Ab 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(RBD)- 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 regions.
- 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.
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-administeration 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 hospitalized as it could worsen their conditions. Therefore, it is beneficial mainly in those which follows above 2 conditions.
The high risk patients should be the first candidates for the drug as there is limited number of supply of 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
- 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 reaction 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
- Arrythmia(bradycardia or tachycardia)
- 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 hospitalization rate to 70% when administered at right time i.e. within 7 days of infection.
- Its 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 Abs, 1200 mg of each.
- One patient has to be administered 600 mg of dose from the vials of each Ab.
- After administration, patient need to be monitored atleast 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 found to be successful.
Also, Germany was first EU country to use antibody cocktail.
In India, Mohabbat Singh, 84 year old, from Haryana became the first one to be administered the drug cocktail.
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 hence a quick effect.
What is passive immunity you ask?
In this, ready-made Ab fight for infection unlike active immunity where our body creates its own Ab which is the path the vaccine takes. They guide our body to create Ab for a given pathogen.(To know more about it, you can read about my 1st article)
- 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).
Hence, you may have understand how it is a breakthrough in development of new treatments towards covid free world.