The COVID-19 pandemic brought about many changes in the way we live, work, and conduct business. This is especially true for those working in the field of public health. COVID-19 exposed shortcomings in the way we track, contain, and treat emergent, rapidly mutating viruses.
Virus Control – A Shifting Paradigm
Over the past century, controlling outbreaks of illnesses has mostly been a matter of vaccination. Chickenpox, smallpox, polio, and other diseases are eradicated or nearly eradicated in the modern world thanks to vaccination.
While vaccination has been instrumental in responding to COVID-19, the virus itself has brought about many challenges. Free vaccines have been widely available for over a year, but the virus continues to spread throughout many communities, spawning treatment-resistant variants as it spreads. Rapid mutations have created a long-term challenge for public health officials. This has left researchers and medical professionals scrambling to find answers: how do you go beyond vaccines to effectively deal with such a rapidly spreading, rapidly mutating virus?
COVID-19 and Polyclonal Antibodies
One of the keys to treating COVID-19 and its variants could be found in polyclonal antibodies. In simplified terms, a polyclonal antibody is made of multiple immune cells that bind to the same antigen by way of different epitopes (the protein structures by which the antibody and antigen bind together). A monoclonal antibody drug, in contrast, is produced using identical clones of a single genetic source, hence the name “monoclonal.”
SAB-185 is a polyclonal antibody currently undergoing trials for the treatment of SARS-CoV-2 in humans. It was developed by SAB Biotherapeutics of South Dakota, and trials have been supported by the National Institutes of Health (NIH) through their “ACTIV” (Accelerating COVID-19 Therapeutic Interventions and Vaccines) initiative.
Data from the trials so far have been promising, with SAB-185 demonstrating an ability to neutralize live SARS-CoV-2 in volunteer subjects. A variety of doses were tested, with placebo groups and several alternate COVID-19 treatments evaluated in the course of the same NIH project. SAB-185’s ACTIV trials are currently entering Phase 3 and have been redesigned in response to the emergent Omicron variant.
The emergence of new variants has a major impact on the efficacy of polyclonal antibody treatments due to the way that antibody treatments function. The therapeutic antibodies must bind to the unwanted antigens by way of protein structures on their surfaces, called epitopes. As viruses like COVID-19 mutate, so do their epitopes. This is how a virus becomes resistant to vaccines and other treatments and can be thought of as analogous to evolution at an increased speed. The well-known “spiky” structure of COVID-19 proteins offers a binding target for antibody-based treatments, but as of yet, no antibody capable of binding to these spikes across all COVID-19 variants has been identified.
Polyclonal antibodies may offer an edge over monoclonal antibodies in the treatment of COVID-19 because they leverage multiple epitopes in the course of binding to antigens. If the necessary epitope features can be identified, such a mechanism could potentially be used to develop a “mutation resistant” form of COVID-19 antibody therapy. A polyclonal antibody of this nature would be able to bind to all variants of COVID-19, potentially including future mutations.
While the fact that SARS-CoV is not well neutralized by SARS-CoV-2 antibodies seems troubling, it also offers an important angle from which further COVID-19 research can be approached. Researchers hope that a broadly effective COVID-19 treatment based on polyclonal antibodies might be the answer.
Sources:
https://www.nih.gov/news-events/news-releases/large-nih-clinical-trial-will-test-polyclonal-antibody-therapeutic-covid-19
https://www.nature.com/articles/s41586-021-04005-0?f
https://www.mdpi.com/2076-393X/9/3/300
https://www.globenewswire.com/news-release/2022/02/25/2392191/0/en/SAB-Biotherapeutics-Announces-Update-to-the-Phase-3-NIH-ACTIV-2-Trial-Design-Evaluating-SAB-185-for-Treatment-of-COVID-19.html
