What Makes Monoclonal Antibodies a Safer Alternative to Rabies Antisera?

Rabies is a viral disease that affects the central nervous system – the brain and spinal cord. It is one of the deadliest infections known. And once the symptoms appear, it is always fatal.

It is caused by the rabies virus, which belongs to the Lyssavirus genus. This virus is present in the saliva of infected animals, such as:

• Dogs
• Bats
• Raccoons
• Foxes
• Skunks
• Cats

It typically spreads through a bite or scratch from an infected animal. The virus enters the body via broken skin or mucous membranes, like the eyes, nose, or mouth. 

Once an infected animal’s saliva comes into contact with a wound or scratch, the virus enters the body. It travels along the nerves toward the brain. This process can take days or months, depending on:

• The location of the bite
• The amount of virus transmitted
• The person’s immune response

When the virus reaches the brain, it causes inflammation. This further leads to neurological symptoms and, eventually, death.

While rabies can be prevented via Post-Exposure Prophylaxis (PEP). This includes:

• Wound cleaning
• Rabies vaccination
• Passive immunization with rabies immunoglobulin (RIG), also known as rabies antisera.

What is Rabies Antisera?

Rabies antisera are antibodies collected from the blood of immunized humans or animals. There are two types:

• Human Rabies Immunoglobulin (HRIG)
• Equine Rabies Immunoglobulin (ERIG)

While both forms of rabies antisera have been effective, they come with some limitations and safety concerns, such as:

• Risk of Allergic Reactions: Equine-derived antisera usually cause hypersensitivity reactions, including anaphylaxis and serum sickness. Despite purification steps, some animal proteins may remain and trigger severe immune responses in humans.
• Batch-to-Batch Variation: Since antisera are biologically derived, they vary between batches. As a result, it has inconsistent antibody potency, which can further affect treatment outcomes.
• Limited Supply: HRIG is expensive and difficult to produce, especially on a large scale. ERIG is more affordable but has a few side effects. So, both types of rabies antisera can’t fulfill the global demand, especially in rabies-endemic regions.
• Blood-Borne Infection Risks: Although rare, there’s a theoretical risk of transmission of infectious agents due to the nature of plasma-derived products.

In order to overcome these challenges, researchers seek a safer alternative to rabies antisera. Here is where monoclonal antibodies come into play.

What are Monoclonal Antibodies?

Monoclonal antibodies (mAbs) are a homogeneous mixture of identical antibodies that are produced from a single clone of immune cells. These antibodies are designed to recognize and bind to one specific epitope (a part of an antigen) with high precision.

They are known for their high specificity and reproducibility. 

For instance:

When it comes to rabies, mouse anti-rabies virus glycoprotein mAbs are used to identify the rabies virus glycoprotein. They block its ability to attach and enter nerve cells. As a result,  this not only provides immediate protection but also time to stimulate the body’s own immune response.

Why mAbs are a Safer Alternative to Rabies Antisera?

Monoclonal antibodies are a safer alternative to rabies antisera because they offer a targeted, consistent, and safer approach to rabies post-exposure treatment, thanks to the following reasons:

Reduced Risk of Allergic Reactions

Rabies antisera are made from human or animal blood. They can cause allergic reactions like:

• Anaphylaxis (a severe reaction)
• Serum sickness
• Other immune problems

Monoclonal antibodies are made in a lab, where environmental factors like temperature, humidity, contaminants, etc., are under control. They do not contain animal proteins. So, the chance of allergic reactions is much lower.

High Specificity and Potency

Antisera contain many types of antibodies. Some of them may not work well against the rabies virus.

mAbs are made to target one specific part of the virus. They stick to it tightly and block the virus from entering nerve cells. This provides strong protection, helping the body fight the virus more effectively.

Consistency Across Batches

Antisera can vary from batch to batch. Some may be weaker than others.

However, monoclonal antibodies are made using a standard process. Each batch has the same strength and quality. There is a negligible risk of wrong prediction. 

Moreover, this eliminates the batch-to-batch variability seen in biologically sourced rabies immunoglobulin. So, this makes mAbs a reliable rabies treatment. This gives more reliable treatment.

Scalable and Sustainable Production

Making rabies antisera takes time and needs donors. Supplies can run out, especially in poor countries.

However, mAbs can be produced in large quantities using recombinant DNA technology. This makes them:

• Easier to scale up during outbreaks
• Less dependent on human or equine donors
• More affordable over time 

Lower Risk of Contamination

Since monoclonal antibodies are produced in controlled lab environments using sterile bioreactors, the risk of contamination with blood-borne pathogens (like HIV or hepatitis viruses) is virtually eliminated. This provides:

• A cleaner safety profile
• Greater confidence in public health settings
• No reliance on blood donations

Potential for Combination Therapy

Researchers are developing cocktails of monoclonal antibodies that can target multiple variants of the rabies virus. This provides:

• Broad-spectrum protection
• High neutralizing activity
• Defense against regional rabies virus strains

This flexibility is hard to achieve with polyclonal antisera, which may not neutralize all circulating strains effectively.

The Bottom Line

While rabies antisera helps treat rabies, it has some side effects. At times, researchers seek a safer alternative – mAbs. This is because they cause fewer allergic reactions, work better against the virus, and are made in a clean, controlled way. Each batch is the same, so the results are more predictable. They can also be made in large amounts without needing human or animal donors. This makes them easier to use, even in countries where rabies is common. With their strong protection and low risk, monoclonal antibodies are a better choice for rabies treatment.