Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, or immunological imprinting, is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a second slightly different version of that foreign pathogen (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. Antibodies or T-cells induced during infections with the first variant of the pathogen are subject to repertoire freeze, a form of original antigenic sin. The phenomenon has been described in relation to influenza virus, SARS-CoV-2, dengue fever, human immunodeficiency virus (HIV) and to several other viruses. History 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 Christian theological concept of original sin. According to Francis as 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." In B cells During a primary infection, long-lived memory B cells are generated, which remain in the body and protect from subsequent infections. These memory B cells respond to specific epitopes on the surface of viral proteins to produce antigen-specific antibodies and can respond to infection much faster than naive B cells can to novel antigens. This effect lessens time needed 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) change through natural mutation. This allows the virus to escape the immune system. The altered virus preferentially reactivates previously activated high-affinity memory B cells and spurs antibody production. However, the antibodies produced generally ineffectively bind to the altered epitopes. In addition, these antibodies inhibit activation of naive B cells that could make more effective antibodies to the second virus. This leads to a less effective immune response and recurrent infections may take longer to clear. Original antigenic sin has important implications for vaccine development. In dengue fever, for example, once a response against one serotype has been established, it is