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Immunological interference – why even “updated” vaccines may find it difficult to keep up with emerging strains of coronavirus
Nurse Natalie O’Connor loads syringes with the Modern COVID-19 vaccine in February 2021. Joseph Prezioso / AFP via Getty ImagesDespite the success and optimism of the new COVID-19 vaccination campaigns being launched worldwide, the emergence of new ones Viral strains threaten to undermine its effectiveness. Indeed, South Africa was forced to rethink its strategy, as its initial vaccine of choice failed to provide protection for an emerging but now dominant viral variant. There is still great hope that mRNA-based vaccines licensed in the United States, with their spectacular effectiveness, will continue to provide protection, despite the harmed targeting of new strains. The jury has yet to decide on viral vector vaccines, such as the new Johnson & Johnson vaccine, but early data showing reduced efficacy against the South African variant has raised alarms. RNA viruses, such as coronaviruses, are known for their ability to mutate. With the continued spread of the infection, the opportunity for the virus to mutate and escape ongoing vaccination efforts remains high. Many in the scientific community were comfortable with the knowledge that mRNA-based vaccines can be quickly modified and redeployed. If our current vaccines fail, we revaccinated individuals with obsolete immunity against the new strains and played whack-a-mole globally as the virus evolved. But it may not be so easy. As an immunologist who studies 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 vaccines. Immune memory, the only thing that offers continuous protection against a virus long after vaccination, can sometimes negatively interfere with the development of slightly up-to-date immune responses. The scientific community needs to anticipate this emerging problem and investigate vaccine approaches known to reduce the potential for viral escape. Dr. Scott Gottlieb, a former FDA commissioner, discusses and adjusts coronavirus variants. Vaccines are designed to generate immune memory In the simplest terms, vaccines are a way of giving your immune system a preview of 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 proteins used in flu vaccines. And more recently, scientists have found ways to provide mRNA “instructions” that tell the body how to make these non-infectious viral components, as was done with the Moderna and Pfizer vaccines against COVID-19. All of these vaccines train your immune system to identify and respond to critical components of a potential invader. An important part of this response is to make your body produce antibodies that will prevent future infections, breaking the person-to-person transmission cycle. However, it takes time for the immune system to generate these protective responses. Your immune system is immensely powerful – capable of destroying 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 rigorously tests the immune cells that produce antibodies – called B cells – to make sure that they are responding with high specificity to the pathogen and not to your own tissue. This process can take weeks. Running carries risks and can be an important component of serious COVID-19 outbreaks. Vaccination gives your body time to carry out this process safely – by generating antibodies against the pathogen that pose no risk to your own cells. The antibodies you make during this period will last for months, and your immune system also remembers how to make them. The establishment of immune memory is a critical component of vaccines. The ability to remember what your immune system responded to in the past gives you a significant advantage when you encounter the same pathogen in the future. But what happens when the virus evolves and that memory becomes “obsolete”? MRNA vaccines work differently than older vaccines. The ‘original antigenic sin’ spectrum During a response 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 run you over. You can produce a type of antibody against the hood, one against the bumper and one against the hubcaps that prevents the wheels from turning. You have produced three types of antibodies specific to the car, but only the antibodies in the hubcap will slow down the car. Your immune system will remember how to produce all three and will not distinguish between them. Now the car virus mutates. It changes the shape of the hubcaps, changes the material or removes them completely. Your immune system will remember the car – but not the hubcaps. The system does not know that aiming at the hubcap was the only important part, so it will increase its attack on the hood and the bumper – minimizing the importance of all other responses. He can “adjust” his cap response, or maybe even develop a new one from scratch, but this process will be slow and certainly of lower priority. By ignoring the new response from the hubcap, the memory of the original car’s immune system not only becomes obsolete, but also actively interferes with the response needed to steer the new car’s wheels. This is what immunologists call ‘original antigenic sin’ – ineffective immune memory that prevents desired responses to new strains of pathogens. This phenomenon is well documented in the flu, where seasonal variations and repeated vaccinations dominate the landscape. However, this type of interference is extremely difficult to quantify, making routine study difficult. Scientists and public health officials cannot ignore this threat in COVID-19 and must get ahead of the virus. Fortunately, there is a way forward. [Get the best of The Conversation, every weekend. Sign up for our weekly newsletter.] Multiple strain vaccinations offer hope To tackle this problem, significant efforts are being made to prioritize the search for a single injection flu vaccine, or a universal vaccine. The goal is to make a vaccine capable of neutralizing many different viral strains at once. To that end, researchers have started to make progress in the development and use of complex multi-strain vaccines, capitalizing on emerging research that shows that if your immune system is presented with multiple versions of the same pathogen, it will tend to choose targets that are shared among they. Presented with a Model-T, Ford F150 and electric Mustang at the same time, your immune system will often choose to ignore differences between targets. Rather than focusing on the hood, or even easily changing hubcaps, your immune system can recognize the shape and rubber of your tires. This altered response not only interferes with the functioning of the three vehicles, but also targets a region of the vehicle that is widespread. You didn’t create a vaccine against Mustangs, you created a vaccine against road vehicles that use tires. Recent knowledge gains in influenza vaccination should be applied immediately to SARS-CoV-2. I am hopeful that the current class of mRNA vaccines will continue to provide protection against emerging strains, but this pandemic has taught us that having hope is not enough. In the past year, governments around the world have stepped up the provision of resources for the basic investigation of immunological responses to COVID-19 and for ongoing vaccination efforts. They had the vision and courage to fund a new mRNA-based vaccination technology that ushered in a new era in vaccination. We will build on that momentum and prioritize research on truly innovative approaches to vaccination that can benefit billions of people around the world. This article was republished 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: The reaction against Johnson & Johnson’s COVID-19 vaccine is real and risky – see how to make its launch a success Two gaps to be filled for the winter wave of 2021-2022 COVID-19 cases Matthew’s research Woodruff is supported by the National Institute of Health. He is also a co-founder of the Jefferson Electorate.