Original antigenic sin

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The original antigenic sin: When the body first encounters an infection it produces effective antibodies against its dominant antigens and thus eliminates the infection. But when it encounters the same infection, at a later evolved stage, with a new dominant antigen, with the original antigen now being recessive, the immune system will still produce the former antibodies against this old "now recessive antigen" and not develop new antibodies against the new dominant one. This results in the production of ineffective antibodies and thus a weak immunity.

Original antigenic sin, also known as antigenic imprinting, the Hoskins effect,

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

human immunodeficiency virus (HIV) [4] and to several other viruses.[5]

History

This phenomenon was first described in 1960 by

Richard Krause:[7]

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

A memory B cell specific for Virus A is preferentially activated by a new strain, Virus A1, and produces antibodies that ineffectively bind to the A1 strain. These antibodies inhibit activation of a naive B cell that produces better antibodies against Virus A1. This effect leads to a diminished immune response against Virus A1 and heightens the potential for serious infection.

During a primary

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

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.[8]

Original antigenic sin has important implications for vaccine development.[9] In dengue fever, for example, once a response against one serotype has been established, it is unlikely that vaccination against a second will be effective. This implies that balanced responses against all four virus serotypes must be established with the first vaccine dose.[10]

Activation of naive B cells that recognize novel epitopes may be attenuated with repeated infection with variant influenza viruses.

2009 pandemic H1N1 influenza vaccine in individuals who had been vaccinated against the seasonal A/Brisbane/59/2007 (H1N1) within the previous three months.[9]

The relative ineffectiveness of the bivalent booster against the SARS-CoV-2 Omicron variant in patients who had previously received COVID-19 vaccines has been attributed to immunological imprinting.[12]

In cytotoxic T cells

A similar phenomenon has been described in

dengue hemorrhagic fever.[14]

Several groups have attempted to design vaccines for HIV and hepatitis C based on induction of CTL response. The finding that the CTL response may be biased by original antigenic sin may help to explain the limited effectiveness of these vaccines. Viruses like HIV are highly variable and undergo mutation frequently; due to original antigenic sin, HIV infection induced by viruses that express slightly different epitopes (than those in a viral vaccine) might fail to be controlled by the vaccine. It has been hypothesized that: if original antigenic sin is a common phenomenon, a naively designed single-component vaccine could conceivably make an infection even worse than if no vaccination at all had occurred. The hypothesized mechanism is that the immune response would be "trapped" in a less effective response. Therefore, a recommendation was made for vaccines with multiple components or that target conserved epitopes.[13]

See also

References

  1. S2CID 26802171
    .
  2. ^
    PMID 33915711
    .
  3. bioRxiv 10.1101/2022.08.29.505743
    .
  4. PMID 12471109
    . Retrieved May 14, 2021.
  5. ^ Deem, Michael W.The Adaptive Immune Response Archived 2008-07-04 at the Wayback Machine Rice University
  6. JSTOR 985534
    .
  7. ^
    PMID 16494715
    .
  8. ^
    S2CID 11685892
    .
  9. ^
    PMID 21813667
    .
  10. PMID 20980526
    .
  11. PMID 19648276
    .
  12. S2CID 255748794
    .
  13. ^
    PMID 9697760
    .
  14. PMID 16517753
    .
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