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Review
. 2021 Dec:1:13-16.
doi: 10.1016/j.clicom.2021.10.001. Epub 2021 Oct 8.

The "original antigenic sin" and its relevance for SARS-CoV-2 (COVID-19) vaccination

Ger T Rijkers  1   2 , Frans J van Overveld  1
Affiliations
Review

The "original antigenic sin" and its relevance for SARS-CoV-2 (COVID-19) vaccination

Ger T Rijkers et al. Clin Immunol Commun. 2021 Dec.

Abstract

Imprinting of the specific molecular image of a given protein antigen into immunological memory is one of the hallmarks of immunity. A later contact with a related, but different antigen should not trigger the memory response (because the produced antibodies would not be effective). The preferential expansion of cross-reactive antibodies, or T-lymphocytes for that matter, by a related antigen has been termed the original antigenic sin and was first described by Thomas Francis Jr. in 1960. The phenomenon was initially described for influenza virus, but also has been found for dengue and rotavirus. The antibody dependent enhancement observed in feline coronavirus vaccination also may be related to the original antigenic sin. For a full interpretation of the effectivity of the immune response against SARS-CoV-2, as well as for the success of vaccination, the role of existing immunological memory against circulating corona viruses is reviewed and analyzed.

Keywords: Antibody dependent enhancement; Corona vaccines; Influenza; Original antigenic sin.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Original Antigenic Sin, illustrated by the immune response to the viral protein SP1. During a primary response to SP1, either during a viral infection or vaccination with an SP1 containing vaccine, specific B cells response will generate plasma cells (PC), producing anti-SP1 antibodies as well as SP1 memory B cells (BM). A subsequent encounter with the same virus, but carrying a mutated SP1 protein, SP1a, will stimulate SP1a primary B cells and may also activate SP1 BM cells. Latter case, termed the original antigenic sin, will result in the production of large amounts of SP1 antibodies, which may bind to SP1a but could be functional inactive.
Fig. 2
Fig. 2
Back boosting of memory B cells of conserved sequences of related proteins. Upper panel shows the specific response of SP1 specific B cells to infection or vaccination. The lower panel illustrates the activation of existing memory B cells against related SP1 proteins from 3 different but related viruses.
Fig. 3
Fig. 3
Antibody dependent enhancement (ADE) of virus infection. Upper panel illustrates ADE during infection and the lower panel shows the mechanism of vaccination induced ADE.
See this image and copyright information in PMC

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