Pathogenic priming

Original antigenic sin (OAS) is a colloquial way of describing how the first exposure to a virus shapes the outcome of subsequent exposures to antigenically related strains.  Notably through vaccination, the immune system is primed by deliberate exposure to respond with a specific antibody.  This impedes its short-term versatility to future exposures of a variant or similar virus because it mounts responses to a now defunct virus.  Immune system responses to a newly infecting variant of a virus may be ineffectual because it is stuck in a mode of producing immune responses specific to the antigen from the initial immunologic priming from a previous exposure. After immunologic priming, the immune response to any subsequent viral exposures will always be suboptimal and the person will be increasingly prone to symptomatic infections.

Depending on the virus, original antigenic sin can occur either with infection or with vaccination. In the case of vaccination, original antigenic sin means not only that the immune responses from vaccination are a mismatch to a newly infecting variant, but also that the immune system fails to adequately adapt its responses to the new variant.

“The term ‘original antigenic sin’ was first used in the 1960s to describe how one’s 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 …

“OAS describes the phenomenon whereby the development of immunity against pathogens/Ags is shaped by the first exposure to a related pathogen/Ag … subsequent infections with similar influenza virus strains preferentially boost the Ab response against the original strain …

“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.”

Simplified example

People whose immune systems were primed by COVID-19 vaccines may experience “breakthrough” infection, they do not mount as robust an antibody response to the nucleocapsid spike protein as people whose immunologic priming is from infection.

Data from the US Centers for Disease Control and Prevention confirm that people who got two or three COVID-19 jabs are more likely to get ill with COVID-19 six to eight months after the last dose than had they gotten none.

Here’s a layman’s summary to illustrate this phenomenon as simply as possible, within the context of COVID-19:

• Exposed to the original Wuhan SARS-CoV-2 strain, your humoral immune system is programmed to produce antibodies against that specific virus. Similarly, if you got the jab, your body will produce antibodies against the viral spike protein formulated into that shot.
• Exposed to the Delta strain, your immune system responds first by boosting the production of the original antibodies, while antibodies specific against Delta are produced in a far lower amount as it takes time for your body to respond to the new strain.
• Exposed to an Omicron variant, your immune system again responds by boosting the original antibodies, while antibodies against Omicron are produced in even lower amounts than those against Delta.

As a result of this process, with each exposure to a new variant, the original antibodies get “back-boosted.” So, over time, those antibodies come to predominate.

The process is (at least theoretically) the same for all vaccinations. Each booster dose back-boosts or strengthens the original antibodies, making them more and more predominant.

The problem is that they may not be effective at neutralizing newer strains (depending on the amount of mutation), thus rendering you more and more prone to symptomatic infection.