Ipsilateral boosting of the COVID-19 mRNA vaccine promotes the positive selection and plasma cells differentiation of pre-existing germinal center B cells

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B918
Abstract ID: 4740

Presenting Author:
Wenxia Jiang , Postdoc at Indiana Univ. Sch. of Med.

Abstract:

COVID19 mRNA vaccines require a prime-boost strategy to stimulate a robust protective antibody response. In our study, we observed that an ipsilateral boost triggered more efficient germinal center (GC) B cell and long-lived plasma cell responses in mice compared to a contralateral boost. To delve into the underlying mechanism, we focused on how these distinct boosting approaches affected pre-existing GC cells induced by the prior vaccination. Examining GC responses two to four days post mRNA booster vaccination, we found that ipsilateral boosting, unlike contralateral boosting, significantly enhanced the positive selection of pre-existing GC B cells, evident through heightened c-MYC expression—a well-established marker of positive selection. Moreover, only ipsilateral boosting enhanced the differentiation of GC B cells into plasma blasts at these early time points. This likely contributed to the rapid induction of higher affinity receptor binding domain (RBD)-specific antibodies observed following ipsilateral boosting. Notably, ipsilateral boosting prompted a rapid expansion of T follicular helper cells (TFH) and a substantial increase in the TFH to T follicular regulatory cells (TFR) ratio four days after the boost. Our results suggest that ipsilateral boosting may directly impact pre-existing GC B and T cells, indicating feasible approaches to optimize vaccine efficacy.