Introduction
The mAb, which has now received emergency use authorization in India by the central drug standards control, is the cocktail drug of monoclonal antibodies, Casirivimab and Imdevimab. It also has gained approval in the United States and other European countries. Developed by Roche India and Cipla, antibody cocktails Casirimivab and Imdevimab act directly on the spike protein of the viral genome of the SARS COV-2 virus. This authorization makes it easier for reducing the hospitalization risk of COVID-19 patients who are at high risk and prone to developing severe COVID symptoms:
It is valuable for older adults above the age of 55-60 years, with type 1 or type 2 diabetes, chronic kidney diseases, hypertension, cardiovascular disease, chronic pulmonary obstructive disease, Immunosuppressive disorders, cancers, chronic liver disease, and asthma. Also, individuals with neurodevelopmental or congenital conditions between the ages of 12 to 17 who are prone to COVID infection, obese individuals with a high BMI >35 can be benefitted from this treatment.
Structure of SARS COV-2 Genome:
The deadly SARS COV-2 genome mainly comprises or encodes four major structural proteins along with accessory proteins and non-structural proteins. The four significant proteins encoded by the viral genome are
1. Spike (S)- Further divided into two subunits S1 and S2 (for invasion and host cell attachment):
i). S1- It has a receptor-binding domain (RBD) that attaches to the ACE 2 host cell receptors (Angiotensin-converting enzyme receptors).
ii). S2- Post binding to the receptors, the S2 subunit manipulates or initiates the viral entry into the host cells apart from membrane fusion as it structurally or conformationally changes as soon as the S1 begins cell binding.
2. Envelope (E).
3. Membrane (M).
4. Nucleocapsid (N).
Mainly, the spike protein that is responsible for mediating host cell attachment and invasion is the target of the monoclonal antibodies, which have been evidently proved to be clinically beneficial and acceptable by physicians.
What Is a Monoclonal Antibody Cocktail?
Casirivimab and Imdevimab are laboratory-made proteins (produced by recombinant DNA technology) or rather IgG1 (Immunoglobulin G-1) directed explicitly to the spike proteins S1 and S2 of SARS COV-2 antigen, thus blocking both the viral attachment as well as the replication in the host cells. They are administered after dilution by Intravenous infusion only after being prescribed by a highly qualified healthcare professional. These IV infusions of mAb’s typically take around 20-30 minutes for administration. However, both Casirivimab and Imdevimab are not authorized for use by physicians, especially in chronic comorbid patients who are hospitalized due to the infection or who require supportive oxygen therapy for COVID-19.
Patients treated with this antibody cocktail should continue to self-isolate and use precautions of necessary distancing, frequent handwashing, proper physical hygiene, and usage of face masks. Each pack of the antibody cocktail contains one vial that totals 2400 mg (1200 mg of Casirivimab and 1200 mg of Imdevimab). The dosage per patient is 1200 mg overall containing 600 mg of Casirivimab and 600 mg of Imdevimab.
Subcutaneous administration of the drug is also possible apart from IV infusion. For the subcutaneous route, four syringes of 2.5 ml (2 each of Casirivimab and Imdevimab) are concurrently administered at four different sites on the abdomen or the thigh region. These antibody cocktail vials are usually stored between 2 degrees to 8 degrees Celsius. Patients are monitored both during the infusion and one hour after the injection by qualified healthcare providers or professionals in a clinical setting. It is done to make sure emergency access to medications are possible by the physician in the possibility of anaphylaxis.
How Do Monoclonal Antibodies Act?
Monoclonal antibody therapies are the only drugs proven efficacious apart from vaccines to treat and prevent COVID infection, especially in high-risk groups like unvaccinated or individuals with multiple comorbidities. These monoclonal antibodies don’t generate host immunity like vaccines. Instead, they have a mechanism of action where the viral antigen gets bound by these mAb’s, thus penetrating and eliminating them faster from the host immune system. A similar technique developed 35 years ago by scientists and researchers was most recently used against the Ebola virus outbreak. The primary reason why physicians are recommending mAb’s is that they are prophylactically effective in preventing the transmission of the SARS COV-2 virus within households.
The monoclonal antibody cocktails also have a longer duration acting potential. For example, AstraZeneca’s monoclonal cocktail uses a half-life extension technique YTE that increases the duration of therapeutic release of these antibodies beyond a specific time limit that makes this treatment potentially three times more durable than conventional antibodies. Research also shows an intramuscular injection of mAbs for immunocompromised cases and in high-risk frontline health workers and staff can last therapeutically in the host immune system for approximately a year.
Availability of mAb:
These monoclonal antibodies are not widely deployed for public use and are approved only for emergency administration by the FDA in the United States. It is used in mild to moderate COVID-19 patients who are non hospitalized and are at severe or high risk of infectious progression that may lead to hospitalization and emergency support. In the recent past, it was selectively administered only to high-profile patients suffering from the novel coronavirus in the United States. Also, it was given for recovered individuals from an active COVID-19 infection as a prophylactic regimen after viral exposure.
The limited and high-cost treatment of these mAbs can be attributed to the logistic difficulties and not the full-fledged nod from the FDA or the central governments to use it prophylactically in the general population. The general public may not be able to afford the high-cost treatment. In addition, its use is questionable due to the ten high production costs that already hamper the limited availability and decrease the extensive scale application of antibody-based therapies.
Against the newer delta variant and its mutations, researchers speculate the presence of monoclonal antibodies to act more effectively and for a longer duration than the COVID vaccine as these mAbs maintain a high defense level against mutating variants of the novel pathogen. One more drawback would be that in people receiving mAb’s, the COVID vaccination should be deferred by 90 days to prevent a vaccine-induced immune response.
What Are the Limitations of Monoclonal Antibodies, Casirivimab and Imdevimab?
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The COVID-19 vaccine is not a replacement for post-exposure prophylaxis with mAb (Casirivimab and Imdevimab).
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It is not permitted to use mAb (Casirivimab and Imdevimab) as pre-exposure prophylaxis to prevent COVID-19.
Conclusion:
Monoclonal antibody cocktail is highly efficacious in high-risk patients prone to coronavirus infection. It is currently being implemented for emergency treatment that would be combative against the emerging variants/strains of the SARS COV-2 pathogen. However, authorization, logistics, and limited supply are the main drawbacks of utilizing mAb’s in the general population.