In America, public health officials, healthcare regulators, the federal government, and conservative politicians normally averse to state intervention in healthcare, are currently sharing common ground in their unstinting support for the use of monoclonal antibodies to treat, and even prevent, COVID-19. According to the US Department of Health and Human Services, 2.17 million doses of monoclonal antibodies have been supplied across America as of 20 September 2021, with 70 per cent of the requests coming from the seven southern “red” low-vaccination states of Alabama, Florida, Georgia, Louisiana, Mississippi, Tennessee, and Texas. Florida’s Governor Ron DeSantis has become particularly vociferous in his support for antibody treatment, having directly overseen the setting of up of the first of 25 state-run monoclonal antibody treatment sites on 12 August 2021. On the other hand, allegations of stockpiling and inequities in distribution of doses have led the Biden administration to take control of monoclonal antibody supplies to ensure equitable distribution across the country, much to the displeasure of leading southern politicians, including DeSantis himself, who has reportedly threatened to approach suppliers directly for antibodies if so required.
Monoclonal antibodies have been around for some time, being first developed in 1975 by Georges Kohler and Cesar Milstein-pioneering work for which they shared a Nobel Prize for Medicine in 1984. These antibodies are now mass produced in laboratories using genetic engineering techniques. The original method involved the fusion in the laboratory of spleen cells (B lymphocytes), obtained from mice injected with the target antigen, with human myeloma (a form of blood cancer) cells in tissue cultures to produce unique and “immortal” cell clones of B lymphocytes (a form of white blood cells). These hybrid cell lines, commonly referred to as hybridomas, then produce identical copies of monoclonal antibodies against the selected antigen. Since the original discovery, advances in recombinant genetic engineering and the use of alternative animal sources for B lymphocytes have led to refinements in techniques for monoclonal antibody production.
Several monoclonal antibodies are currently prescribed for a wide variety of conditions, including certain types of cancers (such as breast cancer), autoimmune disorders, inflammatory bowel disease, among others. All monoclonal antibody names end in -mab, allowing easy recognition . The source sub-stem, included earlier as a prefix to the common -mab stem, has not been used since May 2017, making it more difficult to identify the precise animal source of the antibody in question.
Neutralising monoclonal antibodies can substitute for antibodies that are naturally produced by the human body in response to either infection or vaccination. This method of providing pre-formed antibodies is particularly important for immunocompromised people, who are unable to produce sufficient antibodies on their own, and for those who are not yet fully vaccinated. In the case of SARS-Cov-2, monoclonal antibodies are targeted against the coronavirus’s surface spike glycoprotein, which attaches to ACE2 receptors on human cell membranes, thereby preventing entry of the virus into host cells.
Treatment with monoclonal antibodies does not require admission to hospital only requiring an intravenous infusion, administered over about an hour. Infusion-related reactions (flushing of the skin, itching, difficulty in breathing, a fall in blood pressure) and allergic reactions, including potentially life-threatening hypersensitivity reactions, usually occur during, or shortly after cessation, of antibody administration, but have rarely been reported more than 24 hours after treatment.
On 21 November 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to Regeneron Pharmaceuticals to allow use of its combination of casirivimab and imdevimab (REGEN-COV) to treat mild to moderate COVID-19 symptoms in adults and children aged 12 years and older and weighing at least 40 kilograms. Recipients required to have tested positive for SARS-Cov-2 and to be identified as being at high risk of progressing to severe COVID-19. This followed a randomised, double-blind, placebo-controlled clinical trial in which the antibody cocktail was found superior to placebo in reducing the viral load on day seven in treated patients. Ex-President Donald Trump was one of the early beneficiaries of this new form of treatment. Other monoclonal antibodies soon followed. On 9 February 2021, the FDA issued an EUA for a combination of bamlanivimab and etesevimab (Eli Lilly), followed by an EUA for sotrovimab (Eli Lilly) on 26 May.
Since August 2021, the FDA has issued EUAs allowing post-exposure prophylaxis for immunocompromised people, or those not fully vaccinated, who have been exposed to infection and are at high risk of developing severe COVID-19, while stressing that this treatment is only a temporising measure and not a substitute for vaccination. On 20 August 2021, Ronapreve (casirivimab and imdevimab) (Regeneron/Roche) became the first monoclonal antibody to be authorised for COVID-19 prevention and treatment by the Medicine and Healthcare products Regulatory Agency (MHRA) in the UK, in at-risk seronegative patients lacking adequate antibody levels.
Monoclonal antibody therapy is yet another addition to our growing therapeutic armamentarium against SARS-Cov-2, but not quite the panacea as touted by many of its more enthusiastic supporters. The emergency approval of monoclonal antibodies, still considered to be investigational treatments, does not extend to patients actually hospitalised with severe COVID-19, nor for any form of pre-exposure prophylaxis against infection. But the initial results in suppressing the progression of mild to moderate COVID-19 into severe COVID-19 appear promising and certainly justify their use for this purpose. The potential benefits await confirmation by the results of ongoing trials.
Ashis Banerjee