Original antigenic sin

Original antigenic sin refers to the phenomenon where the first exposure to an antigen shapes the immune system's response to subsequent exposures to related antigens. This concept is particularly relevant in the context of influenza viruses and vaccine development. The term was first coined in the 1960s to describe the observation that the antibody response to a second influenza virus was often dominated by antibodies against antigens of the first virus to which an individual was exposed. This can lead to a less effective immune response to the new virus, as the immune system preferentially utilizes memory responses to the original virus rather than generating a new response to the current strain.

The mechanism behind original antigenic sin involves the immune memory, which is established by B cells and T cells after the first infection or vaccination. When the immune system encounters a new, but related, antigen, it tends to rely on these memory cells rather than generating new ones. This can be beneficial if the subsequent antigens are similar enough to the original, as it allows for a rapid immune response. However, if the antigens are sufficiently different, this reliance on memory cells can result in a suboptimal response to the new challenge.

Understanding original antigenic sin is crucial for the design of effective vaccines, especially for rapidly evolving pathogens like the influenza virus. It suggests that vaccine formulations might need to be tailored not just to the current circulating strains but also consider the immune history of the population to avoid suboptimal immune responses. This has implications for both seasonal influenza vaccines and the development of universal influenza vaccines, which aim to provide broad protection against a wide range of influenza strains.