Original antigenic sin

Original antigenic sin, also known as the Hoskins effect, refers to the propensity of the body's immune system to preferentially utilize immunological memory based on a previous infection when a second slightly different version of that foreign entity (e.g. a virus or bacterium) is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections. The phenomenon of original antigenic sin has been described in relation to influenza virus, dengue fever, human immunodeficiency virus (HIV), and to several other viruses.

This phenomenon was first described in 1960 by Thomas Francis, Jr. in the article "On the Doctrine of Original Antigenic Sin". It is named by analogy to the theological concept of original sin. According to Thomas Francis, who originally described the idea, and cited by Richard Krause:

"The antibody of childhood is largely a response to dominant antigen of the virus causing the first type A influenza infection of the lifetime. [...] The imprint established by the original virus infection governs the antibody response thereafter. This we have called the Doctrine of the Original Antigenic Sin."

During a primary infection, long-lived memory B cells are generated, which remain in the body, and provide protection from subsequent infections. These memory B cells respond to specific epitopes on the surface of viral proteins in order to produce antigen-specific antibodies, and are able to respond to infection much faster than B cells are able to respond to novel antigens. This effect shortens the amount of time required to clear subsequent infections.

Between primary and secondary infections, or following vaccination, a virus may undergo antigenic drift, in which the viral surface proteins (the epitopes) are altered through natural mutation, allowing the virus to escape the immune system. When this happens, the altered virus preferentially reactivates previously activated high-affinity memory B cells and spur antibody production. However, the antibodies produced by these B cells generally ineffectively bind to the altered epitopes. In addition, these antibodies inhibit the activation of higher-affinity naive B cells that would be able to make more effective antibodies to the second virus. This leads to a less effective immune response and recurrent infections may take longer to clear.

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