Ipsilateral immunization after a prior SARS-CoV-2 mRNA vaccination elicits superior B cell responses compared to contralateral immunization
Wenxia Jiang,
Alexander R. Maldeney,
Xue Yuan,
Martin J. Richer,
Scott E. Renshaw,
Wei Luo
Affiliations
Wenxia Jiang
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Alexander R. Maldeney
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Xue Yuan
Department of Otolaryngology – Head and Neck Surgery, School of Medicine, Indiana University, Indianapolis, IN 46202, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Martin J. Richer
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana University Cooperative Center of Excellence in Hematology (CCEH), Indiana University School of Medicine, Indianapolis, IN 46202, USA
Scott E. Renshaw
Department of Family Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Wei Luo
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana University Cooperative Center of Excellence in Hematology (CCEH), Indiana University School of Medicine, Indianapolis, IN 46202, USA; Corresponding author
Summary: mRNA 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.
