Original Antigenic Sin

Lt A.T. Waters: For our sins

Sgt Ellis 'Zee' Pettigrew: Hooyah.
--Tears of the Sun

When a virus infects the body, white blood cells called B lymphocytes (a.k.a. B cells) imprint on specific virus proteins (a.k.a. antigens) presented to them. Subsequently, many of those B cells become 'memory B cells,' specializing in producing antibodies to combat those antigens. 

When different viral infections arrive in the future, memory B cells quickly pour forth antibodies that they learned to produce in the original case, essentially hogging areas around antibodies that slower moving naïve B-cells would use utilize to learn about new viral features. Although the immune system continues to adapt, it does so with 'path dependence.' Stated differently, immune system responses are shaped by the early stimuli that B cells encounter.

This is the central notion of original antigenic sin. Original virus infections during childhood govern antibody responses thereafter. 

The concept of original antigenic sin carries important implications. Different age cohorts in a population are likely to have overlapping or layered immunity to different viral strains. For example, children exposed to the swine flu develop immune responses that differ from a childhood cohort exposed to the Hong Kong flu. Consequently, different generations interlock to attenuate the influence of a particular pathogen.

One reason that flu shots lack effectiveness is that they may have limited power to redirect the adult immune systems against novel influenza strains since those immune systems have long since been primed along a different path by childhood infections.

The influence of original antigenic sin on vaccine effectiveness has been contested, however. Opponents point toward studies suggesting that all cause mortalities decline after administration of flu shots. Counter studies suggest that such research is subject to confounding variables that produce spurious relationships between flu shots and effectiveness.

To the extent that the theory of original antigenic sin is valid, it suggests ominous consequences for policies that encourage or require vaccines across large swaths of populations. Instead of layered, population-wide resistance to successive SARS-2 strains that are certain to evolve as the virus adapts to its environment, inoculating the majority of a population with a vaccine designed to combat narrow strains of the virus is likely to attenuate antibody responses to future variants. Most people will have their primary immune responses to SARS-2 conditioned to the spike protein of the vintage 2020 configuration, leaving them less adaptive capacity moving forward.

Vaccinating children would be particularly problematic. The virus is not a threat to them, and as they become naturally infected with future CV19 strains they will help the entire population develop the layered immunity essential to long term resistance to the virus. By narrowly conditioning childhood immune systems to current strains via the shot, these policies risk creating a perpetual pandemic state.

Of course, it is not outside the realm of possibility that this is precisely what some policymakers may have in mind.