Monoclonal Antibody (mAb) Therapy Against COVID-19

  • SARS-CoV-2 swept the world in 2020, leading to blockades, social distancing, and huge economic losses. In addition, COVID-19 also triggered vaccine, treatment, and diagnostics competition, achieving the approval of the first vaccine based on mRNA technology. The European Union also approved the use of this vaccine in December 2020, only 12 months after the discovery of SARS-CoV-2 and the release of its genetic sequence. Since then, 14 other COVID-19 vaccines using various technologies have been approved or authorized for emergency use in many countries, and more than 60 vaccines are under development.

     

    Although many people view vaccine approval as the end of the pandemic, as of June 7, 2021, only 11.8% of the global population had received the first dose and less than 5% had received two doses. This is largely due to the unfair distribution of vaccines and the fact that vaccines have not yet been approved for use in children. Although Pfizer and BioNTech's vaccines have recently been approved by the FDA and the European Medicines Agency (EMA), which can be used in adolescents 12 years and older. In the absence of widespread vaccination in most countries, other preventive measures and treatments against COVID-19 are essential to stop deaths and reduce the burden on the over-stressed healthcare system.

     

    One promising therapeutic agent for COVID-19 is the monoclonal antibody (mAb). According to the experts about the use of mAb therapy to treat COVID-19, "Vaccines will train the immune system against future infections, while antibody therapy can immediately treat existing SARS-CoV-2 infections. These powerful tools will complement each other to ensure that the majority of the population is protected from the severe impact of COVID-19. "

     

    Benefits of utilizing mAb to treat COVID-19

    The main highlights of mAbs are their specificity and safety. "mAbs are engineered proteins that mimic the immune system to resist harmful pathogens (such as viruses) and have advantages over other treatments for infections because they are artificially created to target specific part of the virus," according to a scientist at Creative Biolabs.

     

    In most cases, the mAb used to treat COVID-19 targets the SARS-CoV-2 Spike (S) protein, a glycoprotein expressed on the virus surface that is necessary for the viral infection process. SARS-CoV-2 infects cells through the interaction between the receptor binding domain (RBD) on the S protein and angiotensin-converting enzyme 2 (ACE2) which acts as a receptor for human cells. By inhibiting this interaction, mAbs prevent the spread of viruses through body tissues, thereby reducing the symptom severity. They also have immunomodulatory abilities to modulate the immune system against infections.

     

    Although recent research shows that many COVID-19 patients develop no symptoms or can recover from mild illness, yet high-risk patients are more likely to develop serious illnesses that require hospitalization, oxygen therapy, and even have the risk of death. When mAb treatment is given in the early stage, it can reduce the progression rate of mild to moderate patients to severe COVID-19. In this way, they can prevent high-risk outpatients from being hospitalized, thereby reducing the burden on the healthcare system. In addition, anti-Spike protein mAb is currently the only available specific treatment method against SARS-CoV-2.

     

    Therapeutic mAbs were proved to be more effective in the early administration of various respiratory infections such as influenza, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola. Not only do they reduce the viral load by inhibiting the entry of viruses into cells, but they can also act as immune rate limiting agents, inhibiting overactive immune responses that can cause damage to tissues, both of which are key functions in reducing morbidity and mortality. Some key mAbs currently under development include tocilizumab, sarilumab, and siltuximab, which are all interleukin 6 (IL-6) inhibitors, and are being evaluated for their ability to fight cytokine storms—large volumes of pro-inflammatory factors called cytokines are released into the blood, which are thought to be the cause of immune-mediated tissue damage and the most severe manifestations of COVID-19, including acute respiratory distress (ARDS) and organ failure. Other immunomodulatory targets include but are not limited to granulocyte-macrophage colony stimulating factor (GM-CSF), CCR5 chemokine receptor, IL-1β and interferon γ (IFN…£), and ongoing research is evaluating their clinical use.

     

    In addition, monoclonal antibodies can supplement vaccines through providing rapid protection against infection, especially for those who may have a weakened immune system or are not eligible for vaccination.