Jiang, WenxiaMaldeney, Alexander R.Yuan, XueRicher, Martin J.Renshaw, Scott E.Luo, Wei2024-06-112024-06-112024Jiang W, Maldeney AR, Yuan X, Richer MJ, Renshaw SE, Luo W. Ipsilateral immunization after a prior SARS-CoV-2 mRNA vaccination elicits superior B cell responses compared to contralateral immunization. Cell Rep. 2024;43(1):113665. doi:10.1016/j.celrep.2023.113665https://hdl.handle.net/1805/41429mRNA vaccines have proven to be pivotal in the fight against COVID-19. A recommended booster, given 3 to 4 weeks post the initial vaccination, can substantially amplify protective antibody levels. Here, we show that, compared to contralateral boost, ipsilateral boost of the SARS-CoV-2 mRNA vaccine induces more germinal center B cells (GCBCs) specific to the receptor binding domain (RBD) and generates more bone marrow plasma cells. Ipsilateral boost can more rapidly generate high-affinity RBD-specific antibodies with improved cross-reactivity to the Omicron variant. Mechanistically, the ipsilateral boost promotes the positive selection and plasma cell differentiation of pre-existing GCBCs from the prior vaccination, associated with the expansion of T follicular helper cells. Furthermore, we show that ipsilateral immunization with an unrelated antigen after a prior mRNA vaccination enhances the germinal center and antibody responses to the new antigen compared to contralateral immunization. These findings propose feasible approaches to optimize vaccine effectiveness.en-USPublisher PolicyImmunologyAntibodyGerminal centermRNA vaccinePlasma cellArticle