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Immune disorders – why even ‘updated’ vaccines struggle to keep up with emerging coronavirus strains
Nurse Natalie O’Connor loads syringes with the Modern COVID-19 vaccine in February 2021. Joseph Prezioso / AFP via Getty Images Despite the success and optimism of the new COVID-19 vaccination campaigns launched worldwide, the emergence of new virals threatens strains undermine their effectiveness. South Africa was indeed forced to reconsider its strategy, as the initial vaccine it had chosen could not protect an emerging, but now dominant, viral variant. The hope is still high that the mRNA vaccines licensed in the US, with their spectacular efficacy, will continue to provide protection, despite the attenuation of new strains. The jury is still looking for viral vector vaccinations, such as the new Johnson & Johnson vaccine, but early data showing reduced efficacy against the South African variant has sounded the alarm. RNA viruses, such as coronaviruses, are known for their ability to mutate. With continued widespread infection, the chances for the virus to change and evade continuous vaccination attempts are still high. Many in the scientific community have felt comfortable knowing that mRNA-based vaccines can be rapidly adapted and redeployed. If our current vaccinations fail, we re-vaccinate individuals with outdated immunity against the new strains and we play a global blow to the virus. But it may not be that easy. As an immunologist studying how antibody responses choose their targets, I am concerned that these “vaccine updates” may be less effective in patients who have already received their original shots. Immunological memory, the thing that provides sustained protection against a virus long after vaccination, can sometimes adversely affect the development of slightly updated immune responses. The scientific community must anticipate this emerging problem and investigate vaccine approaches that reduce the potential for viral escape. Former FDA commissioner Dr Scott Gottlieb discusses coronavirus variants and adaptation. Vaccines are designed to generate immune memory. In the simplest terms, vaccines are a way to give your immune system a look at a pathogen. There are different ways to do this. One way is to inject inactivated versions of a virus, as was done with polio. Another is to use non-infectious viral components, such as the proteins used for flu vaccines. And recently, scientists have found ways to give ‘mRNA’ instructions’ that tell your body how to make the non-infectious viral components, as was done with the Moderna and Pfizer vaccines against COVID-19. These vaccines all train your immune system to identify and respond to critical components of a potential invader. An important part of the response is to have your body produce antibodies that will hopefully prevent future infections, which will break the cycle of person-to-person transmission. However, it takes time for your immune system to respond to those protective reactions. Your immune system is extremely powerful and can destroy dangerous pathogens as well as your own tissue. The risk of accidentally producing antibodies that attack your own body is very real and potentially catastrophic. To prevent this, your immune system carefully tests immune cells that produce antibodies – called B cells – to make sure they respond with high specificity to the pathogen and not your own tissue. This process can take weeks. Its rush carries risks, and may be an important component of the manifestations of severe COVID-19. Vaccination gives your body the time to carry out the process safely – to generate antibodies against the pathogen that pose no risk to your own cells. The antibodies you produce during that time will last for months, and your immune system will also remember how to make them. The establishment of immune memory is a critical component of vaccines. The ability to remember what your immune system has reacted to in the past gives it an important advantage when it gets the same pathogen in the future. But what happens if the virus develops, and the memory becomes “obsolete”? mRNA vaccines work differently than older vaccines. The Ghost of ‘Original Antigen Probe’ During a reaction to a pathogen, such as a virus, your immune system produces large amounts of a limited set of antibodies. Think of a virus as a car trying to drive you. You can produce one type of antibody against the hood, one against the bumper and one against the hub covers that prevent the wheels from turning. You have made three types of antibodies that are specific to the car, but only the wheel cover antibodies slow down the car. Your immune system will remember how to produce all three, and will not distinguish between them. Now the virus engine is mutating. It changes the shape of the hub covers, changes the material or removes it completely. Your immune system will remember the car – but not the wheel covers. The system does not know that the most important part of the wheel cover was aimed, so it will increase the attack on the hood and bumper, which reduces the importance of all other answers. It may “adapt” its hubcap response or even develop a new one from scratch, but the process will be slow and definitely of lower priority. By ignoring the new wheel response, the memory of the immune system to the original car is not only obsolete, but also the reaction needed to direct the wheels of the new car is active. This is what immunologists call ‘original antigenic probe’ – ineffective immune memory that inhibits the desired responses to new pathogen strains. This phenomenon is well documented in influenza where seasonal variants and repeated vaccinations dominate the landscape. However, this type of interference is extremely difficult to quantify, making it difficult to study regularly. Scientists and public health officials cannot ignore this threat in COVID-19 and must come out before the virus. Fortunately, there is a way forward. [Get the best of The Conversation, every weekend. Sign up for our weekly newsletter.] Multiple vaccinations offer hope To tackle this problem, significant efforts are being made to prioritize the pursuit of a single-flu vaccine or a universal vaccine. The goal is to make a vaccine that can neutralize many different viral strains simultaneously. For this, researchers have begun to advance with the development and use of complex multi-strain vaccines, with the benefit of emerging research showing that if your immune system is presented with multiple versions of the same pathogen, it will tend to choose targets that are shared between them. Presented with a Model-T, Ford F150 and electric Mustang at the same time, choose your immune system to ignore differences between the targets. Instead of focusing on the hood, or even on the easily adjustable hub shells, your immune system can recognize the shape and rubber on the tires. This altered response will not only interfere with the function of all three vehicles, but also on a generalized area of the vehicle. You did not create a vaccine against Mustangs, you also created a vaccine against vehicles on the road that use tires. The recent knowledge gains in vaccination of influenza should be applied immediately to SARS-CoV-2. I am hopeful that the current class of mRNA vaccines will continue to protect against emerging strains, but this pandemic has taught us that hope is not enough. In recent years, governments around the world have stepped up to provide resources for the basic investigation into immune responses to COVID-19 and ongoing vaccination efforts. They had the foresight and courage to fund a new mRNA-based vaccination technology that ushered in a new era of vaccination. Let’s build on the momentum and prioritize research on innovative approaches to vaccination that benefit billions of people around the world. This article was published from The Conversation, a non-profit news site dedicated to sharing ideas from academic experts. It was written by: Matthew Woodruff, Emory University. Read more: Setback to Johnson & Johnson’s COVID-19 vaccine is real and risky – here’s how to make its implementation successful. Two gaps need to fill for the winter wave COVID-19 cases in 2021-2022. Matthew Woodruff’s research is supported by the National Institutes of Health. He is also a co-founder of Jefferson’s Electorate.