A new macaque study looked at how immune memory forms after infections with different SARS-CoV-2 variants.
The main pattern is familiar from other viruses -
immune imprinting tends to stay biased toward earlier variants, even after later infections.🧵
The main pattern is familiar from other viruses -
immune imprinting tends to stay biased toward earlier variants, even after later infections.🧵
https://twitter.com/atranscendedman/status/2022349101623624030
The model is useful because it allows sequential infections under controlled conditions (Wuhan - Delta - Omicron), something that’s hard to observe clearly in humans.
Omicron as a primary infection = relatively weak new immune imprint
After first Omicron infection in macaques -
variant-specific anti-Omicron RBD antibodies developed slowly
overall immunogenicity was lower
T-cell responses were also weaker.
After first Omicron infection in macaques -
variant-specific anti-Omicron RBD antibodies developed slowly
overall immunogenicity was lower
T-cell responses were also weaker.
This suggests that a single Omicron infection may not generate particularly strong variant specific protection against reinfection with similar strains.
Prior infection with earlier variants = persistent imprinting
When animals had previous exposure (eg Delta or earlier strains), later infections - including Omicron - tended to boost antibodies targeting Wuhan-like epitopes more strongly than Omicron-specific ones.
When animals had previous exposure (eg Delta or earlier strains), later infections - including Omicron - tended to boost antibodies targeting Wuhan-like epitopes more strongly than Omicron-specific ones.
This pattern reflects what immunology describes as
original antigenic sin (immune imprinting) -
where the first strong antigenic exposure continues to shape responses to later variants.
original antigenic sin (immune imprinting) -
where the first strong antigenic exposure continues to shape responses to later variants.
So even after reinfection with a different variant, the immune system often recalls and amplifies earlier memory responses rather than fully shifting toward new variant-specific targets.
Imprinting here is not specific to Delta.
It reflects the effect of the first strong antigenic exposure - whether that was Wuhan, Alpha, or Delta.
Delta simply represents the last highly immunogenic preOmicron variant in this dataset.
It reflects the effect of the first strong antigenic exposure - whether that was Wuhan, Alpha, or Delta.
Delta simply represents the last highly immunogenic preOmicron variant in this dataset.
Sum:
In this model -
Primary Omicron infection - relatively weak variant-specific imprinting
Earlier variant exposure - lasting immune bias toward ancestral epitopes during later infections.
In this model -
Primary Omicron infection - relatively weak variant-specific imprinting
Earlier variant exposure - lasting immune bias toward ancestral epitopes during later infections.
Urano at al., Pathological characteristics of SARS-CoV-2 variants and immune responses induced in a COVID-19 macaque model. nature.com/articles/s4200…
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