Monoclonal antibodies are a sophisticated class of medical interventions that have transformed the approach to treating various diseases, including infectious diseases and certain cancers. These laboratory-produced proteins are designed to augment the body’s natural defenses, offering a targeted strategy against specific threats. They offer new therapeutic options, especially for patients who may not respond to traditional treatments.
What Monoclonal Antibodies Are
Monoclonal antibodies (mAbs) are laboratory-made proteins that mimic the antibodies naturally produced by the human immune system. Antibodies are specialized proteins that identify and neutralize foreign invaders, such as viruses and bacteria, by binding to specific targets called antigens. The term “monoclonal” signifies that these antibodies are clones, meaning they are exact copies of a single antibody designed to bind to only one particular antigen.
These engineered proteins are created by exposing immune system cells to a specific viral protein, allowing scientists to design antibodies that precisely target a particular virus or infection process. Unlike polyclonal antibodies, which are mixtures derived from multiple immune cell types and can bind to various antigens, monoclonal antibodies offer highly specific targeting. This specificity makes them a powerful medical tool, enabling precise interventions against various conditions, from infectious diseases to cancers.
How They Work Against COVID-19
Monoclonal antibodies specifically designed for COVID-19 target the SARS-CoV-2 virus, which causes the disease. These lab-made proteins attach to the virus’s spike protein, a structure on its surface that the virus uses to enter human cells. By binding to the spike protein, the monoclonal antibodies effectively block the virus from attaching to and infecting healthy cells.
This binding action prevents the virus from replicating and spreading further within the body, thereby reducing the viral load. Lowering the viral load can lead to milder symptoms and decrease the likelihood of the disease progressing to a severe stage that might require hospitalization. Different monoclonal antibodies were developed to target various parts of the spike protein or specific variants of the virus, adapting to the evolving nature of SARS-CoV-2.
Eligibility and Administration
Eligibility for monoclonal antibody treatment for COVID-19 focuses on individuals at high risk for severe illness, hospitalization, or death. This includes adults and pediatric patients aged 12 years and older weighing at least 40 kg who have tested positive for COVID-19 with mild to moderate symptoms and do not require oxygen therapy due to COVID-19. Specific risk factors for severe disease include:
Older age (e.g., 65 years or older)
Obesity (BMI over 25 or 35)
Chronic kidney disease
Diabetes
Immunosuppression
Cardiovascular disease
Hypertension
Chronic lung diseases
Sickle cell disease
Neurodevelopmental disorders
Medical-related technological dependence
Early administration is important for treatment effectiveness. The therapy should be given as soon as possible after a positive COVID-19 test result and within 7 to 10 days of symptom onset. Monoclonal antibodies are administered as an intravenous (IV) infusion, often in an outpatient setting, with infusion duration approximately 30 minutes to over an hour. After administration, patients are monitored for about an hour for potential side effects such as infusion reactions, allergic reactions, fever, nausea, or headache.
Efficacy and Ongoing Use
Monoclonal antibodies were effective in preventing severe COVID-19, hospitalization, and death, particularly when administered early. However, the evolution of the SARS-CoV-2 virus, especially the emergence of new variants like Omicron, has impacted the efficacy of many earlier monoclonal antibody treatments. Many anti-spike protein monoclonal antibodies have shown a decrease in their neutralizing activity against newer circulating variants.
As a result, several previously authorized monoclonal antibody therapies are no longer recommended or authorized for emergency use in the United States due to their reduced effectiveness against prevalent variants. While some older monoclonal antibodies may still be effective against certain variants, the landscape of recommended treatments is constantly changing. Currently, non-monoclonal antibody antiviral treatments with different mechanisms of action are more widely used for treating mild-to-moderate COVID-19. For pre-exposure prophylaxis in specific vulnerable populations, such as immunocompromised individuals, newer monoclonal antibodies like pemivibart (Pemgarda) have received emergency use authorization, providing protection against circulating variants.