Original antigenic sin

The antigen original sin (English: original antigenic sin ) refers to a phenomenon of the antiviral immune response. Come individuals who were previously infected with a virus variant ever, with a second variant of this virus into contact, there is a strong tendency of the immune system to produce antibodies only against those epitopes that were already present on the original version of the virus.


For example, a two year old child infected with influenza virus for the first time, his immune system will attempt to generate antibodies against all epitopes of the viral proteins, in particular antigens of the virus surface. Infected the same person for years or even decades later with a variant of influenza virus, the immune response will be preferentially directed against those epitopes which are present in both virus variants. However, new epitopes, even if they are highly immunogenic, if at all, give rise to a much weaker antibody reaction.

Physiological basis

During a primary infection go from certain activated B cells long-lived memory cells, also called memory cells that produced that remain from subsequent infections in the body for protection - the so-called " immunological memory ": the following scenario from - At the cellular level plays - according to current knowledge. These memory cells are responsive to certain epitopes of viral proteins and produce against that antigen - specific antibodies.

It is now possible that the immunity- forming surface structures, the antigens of certain viruses, such as influenza or HIV which undergo changes during the period between primary infection and subsequent secondary infection, called antigenic drift. When this occurs, the modified virus may further comprise epitopes, memory B cells are able to activate and induce antibody production.

The antibodies produced by these B- lymphocytes but bind with high probability to the modified mutant epitopes of new virus with a much lower efficiency, with lower affinity. In addition, the existing directed against the initial virus antibodies appear to the immune responses of naive B cells that have specificity for the existing viral variants to new epitopes to suppress, - what is the actual antigen original sin.

It is believed that these naive B cells are actively inhibited in their development, so that no antibodies against the new determinants can be formed. This can in turn lead to a weakening of the immune response and a more protracted phase of the disease, as a potentially effective response ( against new epitopes) is omitted.

Nevertheless, it can be meaningful and useful, this reaction pattern because memory B cells can respond as part of the immune memory is much faster and more efficiently to the new viral attack as naïve B cells, in contrast to the immediately responsive memory cells after a few days can provide adequate amounts of antibodies are available. In addition, increasing with repeated contact with a known antigen, both the affinity and the amount of the antibody to. This is because the DNA of the B cells is, according to the so-called primary response somatic hypermutation, before the cells into antibody -forming plasma cells. Furthermore find a selection by antigens held in the germinal centers.

The antigen original sin will only fail to bear when a previously infected person is exposed to a new virus variant which lacks all of the original epitopes ( influenza ) virus. There are no pre-existing antibodies that could bind to the virus, so that then can react to naive B- cells.

New insights

At an annual booster dose with a current virus strain could be shown that the induced influenza virus -specific antibodies have the strongest affinity to that contained in the vaccine virus strain and not to the original variant of the virus, as would be expected in the case of the interaction of the antigen original sin. It is concluded that the antigen original sin, not a common phenomenon in normal healthy adults receiving a Influenzavakzinierung.

Application in the diagnosis

The phenomenon of antigen original sin can be in certain cases, be useful for the serological diagnosis of viral infections.

Books and References

  • Charles A. Janeway, Jr. et al.: Immunobiology: the immune system in health and disease, Garland Publishing, 5th edition, New York 2001, ISBN 0 - 8153-3642 -X and from this the sections: 10-25. In immune individuals, secondary and subsequent offer responses are mediated Solely by memory lymphocytes and naive lymphocytes not by
  • 14-22. Attenuated microorganisms can serve as vectors for vaccination against many pathogens