SARS-CoV-2-targeting monoclonal antibody therapies: A complementary strategy to vaccination.
Vaccines are a cornerstone of the battle against COVID-19, caused by SARS-CoV-2 virus. However, some people cannot get vaccinated for safety reasons (e.g., allergies, contra-indications) or they may not have an adequate immune system (e.g., immunocompromised, pre-existing conditions). Also, even though vaccines against SARS-CoV-2 deliver high initial protection, they quickly wane over time, leading to breakthrough infections. In combination with the emergence of new variants this requires frequent booster campaigns, leading to compliance issues. In fact, many of the people who were initially vaccinated did not opt for a booster.
Moreover, vaccines may have yet unknown side-effects that might only become apparent after many years of use. Even if that is only perception, it still means that many people are hesitant to get vaccinated. Especially when they assume their individual risk of serious illness is limited anyway. An issue now even more apparent with the rise of the less virulent Omicron variant. Together with other societal issues, like misinformation and government distrust, this will lead to continued viral spread (ref.1). Also, vaccine inequity is not helping.
So, not everybody can be fully protected by a vaccine, or would even like to get vaccinated in the first place. Therefore, many people remain at risk of severe disease. In fact, 100.000 serious cases of COVID-19 are still reported every day, even now Omicron dominates (ref.2). A huge unmet clinical need since 10.000 or so of these cases will be fatal. And, as Omicron is more transmissible, worldwide mortality, and pressure on hospitals, will remain high in the foreseeable future.
Also, high prevalence will enhance the emergence of new variants, which impacts the efficacy of current vaccines. Also, it is possible that new variants following Omicron will be more virulent again. In fact, all variants so far emerged at times of high infection rates Going back to the drawing board to develop new, or even adapted, vaccines takes time, making it a rat race. All this means that we need alternatives to vaccination if we are to get a long-term grip on the COVID-19 pandemic (ref 3,4,6). Moreover, pandemics are likely to occur with increasing frequency in the coming decades.
Antibody therapies can be used in the same context as vaccines, as a prophylactic treatment, preventing infection and disease. As antibody therapies work immediately, they are particularly useful when there is a high expectancy of contracting a disease in the immediate future. Vaccines take weeks to be fully effective as it requires the recipient’s body itself to build an appropriate immune response.
Moreover, because of their short-term applicability, they can also be used as a viral inhibitor after people have already contracted a virus. In fact, this is currently the primary use for SARS-CoV-2-targeting antibodies in the clinic. Importantly, if it is clear someone already has a disease, ethics change and treatment becomes more acceptable. Vaccination is always tricky from an ethical standpoint because you treat, and induce a risk, before infection even occurs. So, people who oppose vaccination from that point of view might in fact be willing to opt for antiviral treatment.
Here it is important to note that antibodies block viruses in the blood or in tissues before they can enter a cell. Therefore, antibodies do not influence a cell’s biology and side-effects are not expected. Other types of viral inhibitors work downstream of cellular infection and target the intracellular processes that the virus needs to replicate, but also influence the cell’s normal function (ref.5). Treatment with viral inhibitors that act this late in the infection process, like the so-called COVID-pills for example, will thus have side-effects (see figure).
Also important to note is that most antibodies produced for this kind of therapy are derived from human B-cells. Therefore, adverse reactions upon administration of pure human antibody products are not expected.
So, because antibodies are relatively safe, work immediately and can either be given prophylactically or as a treatment, they are the superior treatment option around the initial stages of disease. Also, an antibody treatment can consist of several different antibodies, given as a cocktail, which will make it less prone to loss of efficacy against new variants. To manage any disease, and especially COVID-19, a full complement of armouries is required that address the different technical and societal problems. Antibodies are a key part of that armoury.
Literature:
1. https://www.nature.com/articles/d41586-021-03569-1
2. https://www.worldometers.info/coronavirus/
3. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02790-2/fulltext
4. https://www.weforum.org/agenda/2022/01/covid-19-pandemic-experts-what-next/
5. https://www.nature.com/articles/d41586-022-00112-8
6. https://www.science.org/content/article/after-omicron-some-scientists-foresee-period-quiet
7. https://www.nature.com/articles/d41586-022-00210-7
8. https://www.nature.com/articles/d41586-022-00200-9
9. https://www.nature.com/articles/d41586-022-00220-5
More background can also be found in previous blogs. For example:
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