Any extracts used in the following article are for non commercial research and educational purposes only and may be subject to copyright from their respective owners.
Original Antigenic Sin: How First Exposure Shapes Lifelong AntiâInfluenza Virus Immune Responses (2019)
Abstract
The term âoriginal antigenic sinâ (OAS) was first used in the 1960s to describe how oneâs first exposure to influenza virus shapes the outcome of subsequent exposures to antigenically related strains. In the decades that have passed, OAS-like responses have been shown to play an integral role in both protection from and susceptibility to infections. OAS may also have an important deterministic role in the differential efficacy of influenza vaccine responses observed for various age cohorts across seasons. In this article, we review how the understanding of OAS has progressed from its initial description and highlight important outstanding questions in need of further study.
Introduction
Original antigenic sin (OAS) describes the phenomenon whereby the development of immunity against pathogens/Ags is shaped by the first exposure to a related pathogen/Ag.
The original âoriginal antigenic sinâ
The term was first coined by Thomas Francis in 1960 (1). In his seminal study, Francis observed that hemagglutination inhibition assay titers were highest against seasonal influenza strains to which specific age cohorts had first been exposed (2). These observations were supported by serum absorption experiments, which confirmed that the vast majority of antiâinfluenza virus Abs in a population were cross-reactive against the pioneer strain of that age group (3).
Taken together, these data led Francis to postulate that subsequent infections with similar influenza virus strains preferentially boost the Ab response against the original strain (2). Although OAS has often historically been depicted as a problematic response, recent data have demonstrated that, in certain contexts, eliciting OAS may also be beneficial.
The critical role of primary exposure in shaping the composition of the Ab repertoire was not only observed in humans after influenza virus infections; this phenomenon was also observed in animal models and in the context of other infectious agents. For example, additional serum absorption experiments in ferrets infected in succession with three different influenza virus strains demonstrated that nearly all of the host Abs after the infection series were reactive against the first strain, only a fraction of serum Abs could be absorbed by the secondary virus, and fewer yet by the tertiary virus (3). These results could be replicated using sera of human donors who had been vaccinated against various influenza virus strains (3â6) and also using sera from rats that had been serially infected (7). In addition to influenza virus infections, OAS has also been reported in children who were exposed to sequential dengue virus infections (8). In all cases, the manifestation of OAS is fundamentally dependent upon the relatedness of Ags between primary and secondary infections as this phenomenon is not observed in the context of sequential exposure to distantly related (or unrelated) Ags (9).
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Spike protein (inc vax) induced immunodeficiency & carcinogenesis megathread #8: Original Antigenic Sin: How First Exposure Shapes Lifelong AntiâInfluenza Virus Immune Responses
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Any extracts used in the following article are for non commercial research and educational purposes only and may be subject to copyright from their respective owners.
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Original Antigenic Sin: How First Exposure Shapes Lifelong AntiâInfluenza Virus Immune Responses (2019)
Abstract
The term âoriginal antigenic sinâ (OAS) was first used in the 1960s to describe how oneâs first exposure to influenza virus shapes the outcome of subsequent exposures to antigenically related strains. In the decades that have passed, OAS-like responses have been shown to play an integral role in both protection from and susceptibility to infections. OAS may also have an important deterministic role in the differential efficacy of influenza vaccine responses observed for various age cohorts across seasons. In this article, we review how the understanding of OAS has progressed from its initial description and highlight important outstanding questions in need of further study.
Introduction
Original antigenic sin (OAS) describes the phenomenon whereby the development of immunity against pathogens/Ags is shaped by the first exposure to a related pathogen/Ag.
The original âoriginal antigenic sinâ
The term was first coined by Thomas Francis in 1960 (1). In his seminal study, Francis observed that hemagglutination inhibition assay titers were highest against seasonal influenza strains to which specific age cohorts had first been exposed (2). These observations were supported by serum absorption experiments, which confirmed that the vast majority of antiâinfluenza virus Abs in a population were cross-reactive against the pioneer strain of that age group (3).
Taken together, these data led Francis to postulate that subsequent infections with similar influenza virus strains preferentially boost the Ab response against the original strain (2). Although OAS has often historically been depicted as a problematic response, recent data have demonstrated that, in certain contexts, eliciting OAS may also be beneficial.
The critical role of primary exposure in shaping the composition of the Ab repertoire was not only observed in humans after influenza virus infections; this phenomenon was also observed in animal models and in the context of other infectious agents. For example, additional serum absorption experiments in ferrets infected in succession with three different influenza virus strains demonstrated that nearly all of the host Abs after the infection series were reactive against the first strain, only a fraction of serum Abs could be absorbed by the secondary virus, and fewer yet by the tertiary virus (3). These results could be replicated using sera of human donors who had been vaccinated against various influenza virus strains (3â6) and also using sera from rats that had been serially infected (7). In addition to influenza virus infections, OAS has also been reported in children who were exposed to sequential dengue virus infections (8). In all cases, the manifestation of OAS is fundamentally dependent upon the relatedness of Ags between primary and secondary infections as this phenomenon is not observed in the context of sequential exposure to distantly related (or unrelated) Ags (9).
Full paper:
https://www.jimmunol.org/content/202/2/335
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