Thread by @vipintukur

An interesting study!

Researchers investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including 3rd dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S & Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. 1/

They analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. 2/

Antibody breadth against viral variants is less after infection compared to all vaccines evaluated, but improves over several months. 3/

Antigenic imprinting: Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. 4/

In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA & spike antigen up to 8 weeks post-vaccination in some cases. 5/

However, the most significant finding of the study was wrt ‘Antigenic Imprinting’ or the “Original Antigenic Sin” (OAS), a phenomenon hated by the most experts! 6/

“that prior vaccination w/ Wuhan-like antigens followed by infection w/ Alpha or Delta variants gives rise to Ab responses w/ apparent Wuhan-specific imprinting manifesting as relatively ⬇️ responses to variant virus epitopes, compared to unvaxxed infected w/ those variants. 7/

This finding may have huge implications since the current booster vaccinations are still based on the Wuhan-Hu-1-like antigens!! The Omicron’s spike is highly mutated in comparison to Wuhan’s spike. 8/

No wonder the vaccine manufacturers are in the process of evaluating updated vaccines encoding sequences from one or more circulating variants. 9/

The study also acknowledges this: “Initial results from 3rd dose boosting with Beta spike-encoding mRNA vaccines after prior 2-dose mRNA-1273 vaccination are consistent with the findings of significant imprinting of serological responses by the first antigen encountered….10/

…..indicating that vaccine-derived imprinting affects subsequent antibody responses stimulated by vaccination as well as infection. 11/

The extent to which vaccine boosting or infection w/ diff variants will effectively elicit Ab responses to new epitopes, or rather increase responses to epitopes of antigens encountered previously, as in the “original antigenic sin” will be an important topic of ongoing study 12/

The degree of #imprinting may depend on the particular variants and the order in which they are introduced to the individual’s immune system, and the number of exposures, such as the number of vaccine doses received. 13/

Additional data for evaluating the magnitude of these effects & their consequences for protection from infection are likely to become available in coming months, as people w/ diff histories of SARS2 vaccination or variant infection become infected w/ highly mutated #Omicron 14/

However, the very high spike-specific IgG concentrations generated by mRNA vaccination & periodic boosting may be able to compensate
for relatively ⬇️ binding to new viral variant antigens, potentially ⬇️ the public health impact of Ab response imprinting. 15/

Taken together, #SARS2 antibody specificity, breadth and maturation are affected by #imprinting from exposure history, and distinct histological and antigenic contexts in infection compared to vaccination. 16/

cell.com/cell/fulltext/…