After SARS-CoV-2 booster dose memory B cells have adapted to Omicron

Memory B cells never forget recurrent viral exposure, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is no exception. medRxiv* Preprint survey. Vaccination and previous infections appear to activate long-lived memory B cells and shape them into receptor-binding domain (RBD) -specific B cells. After the third vaccination, the existing Memory B cells became cross-reactive and successfully bound to the Omicron spike protein.

study: Priority expansion during boost of cross-reactive “existing” switched memory B cells that recognize SARS-CoV-2 omicron variant peplomer proteins..

Features of memory and effector B cell subsets

During the study, researchers from various institutions in the United States and South Africa were not infected with subjects who had not been vaccinated with the mRNA vaccine (BNT162b2 or mRNA-1273, respectively) before and 1-2 weeks after vaccination. A fresh blood sample from a small group of subjects was examined. (Postbacks).

Two spike-specific tetramer probes were generated to identify and classify post-vaccination memory and effector B cell subsets. There were 12 clusters identified, but clusters 7 and 9 were classified as high or low for CD27, for a total of 14 clusters.

Effector B cell subsets and switched memory B cell subsets can be found through expression of specific surface proteins such as CD21, CXCR5, CD11c, and CD85j.

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Heterogeneous spike-specific B cells appear after mRNA vaccination. A) Overview of early flow cytometry studies using spike-specific probes and bias-free clustering. B) UMAP dimension displaying all spike-specific B cells from previously unexposed healthy individuals (n = 6) and post-vaccinated dose # 2 (n = 6) pairs from the same individual. Reduction. The plots are color adjusted based on pre-vaccination (Pre-Vax) and post-vaccination (Post-Vax) time points. C) The same UMAP heatmap overlay of Figure B showing the relative expression patterns of IgD, CD27, CD38, CD20, CD21, CXCR5, CD11c, and CD85j. D) Overlay of color coordination clusters between spike-specific B cells identified using phenograph. E) Histogram showing relative contributions from double negative B cells (CD27Negative) and switched memory B cells (CD27 +) between phenograph clusters 7-10. F) Contour diagrams of clusters 7-10 showing the relative expression of CD21 and CD11c.

Proliferation of Memory B cells after vaccination and COVID-19 infection

In people who were later infected with SARS-CoV-2 and vaccinated, the team noticed the presence of spike-bound circulating B cells, which normally attach to them for at least 2-3 months after vaccination. Induction of spike-bound circulating B cells was associated with a change in the CD27 + SWM type phenotype between spike-bound B cells compared to pre-vaccinated B cells.

Among all the changes, vaccination induced the proliferation of IgDCD85j + CD27 + B cells. B cell proliferation persisted for several months after vaccination. IgDCD85j + CD27 + B cells were also found in convalescent patients with COVID-19.

IgDCD85j + CD27 + B cells were not detected or vaccinated in uninfected individual plasma samples. However, researchers have pointed out that these cells do not last more than 6 months after vaccination, suggesting that they are effector B cells rather than memory B cells.

Another group of B cells, IgD-CD27 + CD85j-CD38int, expanded most after vaccination and infection.

Change to existing dormant memory B cells

Uninfected and unvaccinated individuals showed high levels of pre-existing spike-bound B cells targeting SARS-CoV-2.However, exposure only to other seasons coronavirus It becomes difficult to recognize Spike protein Of other coronaviruses such as SARS-CoV-2.

Numerous spike-bound B cells are found in IgD + CD27- “naive” gates, unswitched memory populations, “switched memory” B cell gates, and IgDCD27-switched CD27-B cell populations.

The majority of spike-bound B cells targeting SARS-CoV-2 and Omicron mutants are composed of naive follicular B cells. Unvaccinated, uninfected individuals lack RBD-binding B cells.

After vaccination or infection, the number of spike-bound naive follicular B cells is reduced, suggesting proliferation of other B cells and potential activation of spike-bound naive follicular B cells as needed.

A small portion of spike-bound B cells dormant unswitched memory B cells composed of marginal zone B cells. However, the proportion of marginal zone B cells does not decrease after infection and vaccination, suggesting that activation of this naive B cell population is restricted or not at all.

Infection and vaccination also caused the decline of the existing dormant CD27 + switched memory B cell compartment. However, the existing CD27-negative switch memory B cell compartment of spike-binding protein expanded further after vaccination and infection.

Compared to receptor-bound B cells targeting wild-type SARS-CoV-2, the existing CD27 dormant switch memory B cell compartment is one of the most predominant and long-lasting. antigen-A specific memory B cell population of individuals vaccinated 6 months after vaccination and prior to booster vaccination.

Cross-reactivity of B cell memory population to Omicron

Six months after vaccination, the majority of existing memory B cells were transformed into RBD-bound memory B cells. Researchers also observed that RBD-binding B cells were the most predominant among vaccinated individuals.

Given the increase in Omicron-related COVID-19 cases, researchers investigated how booster shots affect the effects of memory B cells on new concerns.

Boost did not increase the frequency of RBD-bound B cells that recognize Omicron’s RBD. However, it induced the differentiation and expansion of existing switched memory B cells such as CD27 + and CD27-. In addition, boosters increased the frequency of wild-type spike-bound B cells that target and expand to bind to Omicron.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they have not been peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.