Researchers are infusing patients with blood products containing antibodies in hopes they will recover, Our Q&A with Charles River’s Katherine Vousden.
To fight a virus our immune system generates Y-shaped proteins, called antibodies, which latch onto the surface of the virus and inactivate or neutralize it. Many preventive vaccines are designed to induce these antibodies as a way of shielding us from exposure to a pathogen.
But antibodies can also be used to treat viruses. During the COVID-19 pandemic, we’ve been hearing a lot about how doctors are infusing patients with blood products containing antibodies in hopes it will help them recover. While we know vaccines that induce antibody protection work, the literature on how well therapeutic uses perform is still premature. Fortunately, many studies are underway and we should begin to gain a better understanding of whether this is a viable option for severely ill COVID-19 patients.
To answer some common questions people might have about how this therapy works, we interviewed Katherine Vousden, PhD, Science Director at Charles River and an expert in antibodies.
Q: It may be awhile before researchers identify an effective treatment or preventive vaccine for COVID-19. In the interim, some doctors have been giving patients transfusions of antibodies obtained from recovered patients. What is the rationale for this approach?
A: When you are infected with a virus your body mounts an immune response to help fight it, and a part of that immune response is the generation of antibodies able to neutralize, or prevent, the virus from infecting more cells. However, if you are immune-compromised or elderly, this response is less robust or even absent. The good news is that, in individuals that have successfully mounted a healthy immune response to the virus, these antibodies hang around and prevent you being infected again. The theory is that you can isolate the fraction of blood that contains these antibodies (plasma) from recovered patients, and infuse it into those individuals who have a compromised immune response. The antibodies present in the donor plasma will be able cure the new recipient of their viral infection. This type of treatment is called ‘convalescent plasma therapy’.
Q: When you give a sick patient antibodies does it help them fight SARS-CoV-2?
A: Once antibodies have been administered to a sick patient, the effects can be very rapid. As well as blocking virus from entering new cells, once bound to virus the antibody can direct it for clearance by other specialist cells of the immune system. So not only is the virus neutralized but it is also destroyed. It should be noted though, that the lung damage caused by the viral infection can persist long after the virus is cleared – leaving patients struggling with respiratory symptoms and tiredness for many more weeks.
Q: What does the literature tell us about how effective these antibody infusions are against COVID-19?
A: It’s a little early for many robust studies on convalescent plasma therapy to have been completed and reported on for COVID-19, however there are promising data published on a very small pilot study of 10 severe patients.
The authors of this peer-reviewed study show that one dose of convalescent plasma was well-tolerated (i.e. safe) and led to the rapid improvement of clinical symptoms in these patients after 3 days, and disappearance of detectable levels of virus at 7 days after dosing. There are limitations reported with this study – not least the very small sample size – but it’s certainly very promising early data. There are a large number of similar trials on-going in various hospitals around the world, so it’s definitely one to watch.
Q: Are there individual genetic differences that might hamper the efficacy of these treatments?
A: We don’t yet understand why it is that the same virus in one patient can produce mild symptoms, versus acute respiratory failure in someone else – even once any known underlying disease or age factor is taken into account. Ultimately there may be genetic or even environmental factors found to be linked to disease severity, and these may also influence how effective any one treatment is against it, but this research is all at an early stage.
Q: Do we currently use this strategy against other diseases?
A: Convalescent plasma treatment has been used for many years to successfully treat a wide range of viral infections, including Severe Acute Respiratory Syndrome (SARs), Middle-Eastern Respiratory Syndrome (MERs) and Ebola epidemics.
Q: Are there limitations to this type of plasma therapy? If so, are there other ways that antibodies can be generated that might offer hope against covid-19?
A: One limitation with convalescent plasma therapy is getting hold of enough plasma from recovered patients to offer it widely as a treatment. Another limitation is the consistency in antibody titers and consistency of viral neutralization activity in plasma between donors. Both these limitations can be overcome through recombinant antibody engineering and manufacturing approaches.
Antibodies can be individually isolated and characterized from specific antibody expressing cells (B-cells) isolated from recovered patients – or identified through other antibody isolation methods such as phage display or mouse immunization. These can then be produced and characterized in a laboratory before being manufactured at an industrial scale.
This removes plasma donation as a bottle-neck and also allows for the antibodies to be carefully formulated and then dosed at optimal concentrations to achieve the best results.
Q: How are the antibodies chosen for these novel drugs?
A: Any one patient will produce many different antibodies to COVID-19 but not all of them will be neutralizing. By use of next generation sequencing and high-throughput screening methods, the entire repertoire of antibody responses from many different recovered patients can be explored, and only the best antibodies taken forward for further study and ultimately treatment.
These recombinant antibodies can be delivered individually, or combined into cocktails of multiple antibodies. The main thing is that each antibody dosed is at a very specific and tightly controlled concentration for maximum effect.
Q: Are there currently any strategies to give at-risk individuals infusions of antibodies as a preventive measure in case of exposure?
A: In theory, the same antibodies that can be given as a treatment could also be optimized for prophylaxis – to prevent viral infection in high-risk individuals. This may be a useful alternative to vaccination, in those individuals who may not be able to mount a very effective immune response. There are prophylactic antibodies against a number of viruses already on the market (for example Synagis ™ for prophylactic protection against Respiratory Syncytial Virus in high risk infants), which gives hope that the same may one day be true for COVID-19.
Antibody expert Katherine Vousden joined Charles River in early 2020 as a Science Director for Discovery, where she is leading the integration of large molecule projects. She was most recently an Associate Director at AstraZeneca within the Department of Antibody Discovery and Protein Engineering.