Monoclonal antibodies (mAbs) are specialized, laboratory-produced proteins designed to mimic the body’s natural immune response. They provide passive immunity, offering immediate defense against disease. This technology has played a significant role in the global response to the SARS-CoV-2 virus, providing both treatment and prevention options for COVID-19.
How Monoclonal Antibodies Work
Monoclonal antibodies are engineered to target a specific part of the invading virus with high precision. For SARS-CoV-2, the target is the spike protein, which the virus uses to attach to and enter human cells. Scientists design the mAb to bind tightly to the spike protein’s receptor-binding domain. This binding action effectively neutralizes the virus by preventing it from interacting with the human cell receptor known as ACE2. The spike protein acts like a key, and the ACE2 receptor is the lock, allowing the virus entry into the cell. When the mAb attaches to the spike protein, it blocks the key from turning in the lock, stopping the infection process.
Application in COVID-19
Monoclonal antibodies have been used in two primary ways: as a treatment for active infection and as a preventative measure. Treatment is intended for individuals who have recently tested positive and are experiencing mild to moderate symptoms. The goal is to administer the antibodies early in the disease course, before the infection progresses to a severe stage. The second application is pre-exposure prophylaxis, a method of prevention for certain high-risk groups, specifically immunocompromised individuals who may not generate a sufficient protective antibody response from vaccination. For both treatment and prevention, the introduction of ready-made antibodies provides an immediate defense, helping to control the viral load or prevent infection from taking hold.
Patient Eligibility and Administration
Eligibility criteria are strictly defined to ensure mAbs reach the patients most likely to benefit. To qualify for treatment, an individual must be at high risk for progressing to severe COVID-19. This typically includes those with underlying medical conditions such as obesity, chronic kidney disease, or immunosuppressive diseases. Furthermore, the patient must be non-hospitalized and not require supplemental oxygen for COVID-19 symptoms, as treatment is most effective in the early stages of viral replication. Timing is a critical factor; treatment must be initiated within a narrow window, usually within five to seven days of symptom onset or a positive test. Administration is often done through an intravenous infusion in an outpatient clinic or infusion center, followed by a mandatory observation period to monitor for immediate reactions.
Current Authorization Status
The effectiveness of monoclonal antibodies is highly susceptible to the continuous evolution of the SARS-CoV-2 virus. As the virus mutates, particularly in the spike protein region, older authorized mAbs often lose their ability to bind to new variants, rendering them ineffective. This dynamic requires the U.S. Food and Drug Administration (FDA) to constantly review and update the Emergency Use Authorization (EUA) status for these products. Many initial treatment-focused monoclonal antibodies were withdrawn because they lacked sufficient activity against newer, dominant variants, such as the Omicron sublineages. Currently, authorized mAbs are primarily focused on pre-exposure prophylaxis for the most vulnerable populations. For example, Pemivibart (marketed as Pemgarda) has received an EUA for the prevention of COVID-19 in moderately to severely immunocompromised adolescents and adults who are unlikely to mount an adequate immune response to vaccination.