Burmas Lauren, Lee Wen Shi, Kelly Andrew, Webster Rosela, Esterbauer Robyn, Kent Stephen J, Wheatley Adam K, Juno Jennifer A, Tan Hyon-Xhi
Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
J Immunol. 2025 Mar 9. doi: 10.1093/jimmun/vkae067.
Human clinical trials have reported immunological outcomes can differ between ipsilateral (same side) and contralateral (alternate sides) prime-boost vaccination. However, our mechanistic understanding of how keeping or shifting the anatomical sites of immunization impacts the resultant germinal centers (GCs) and antibody responses is limited. Here, we use an adjuvanted SARS-CoV-2 spike vaccine to dissect GC dynamics in draining lymph nodes and serological outcomes following ipsilateral or contralateral prime-boost vaccination in C57BL/6 mice. Contralateral vaccination elicited independent GCs at distinct lymph nodes, where robust secondary GCs only appeared upon secondary distal vaccination, while ongoing GCs from the primary site were not boosted. In contrast, ipsilateral vaccination resulted in sustained GC activity. Ipsilateral vaccination accelerated the development of antibody titers against ancestral (wild-type [WT]), Beta, and BA.1 but were later comparable between ipsilateral and contralateral groups in terms of magnitude, durability, and neutralization capacity beyond 28 d. Using a heterologous SARS-CoV-2 WT/BA.1 spike prime-boost model, cross-reactive GC responses were generated against WT and BA.1 spike, with analogous serological and GC dynamics to our homologous model. Within the cross-reactive GC B cells, differential recognition of WT and BA.1 antigens was observed and were further compartmentalized in primary or secondary GCs, depending on ipsilateral or contralateral regimes. Collectively, maintaining a common prime-boost site augments the kinetics of memory B cell recall and transiently drive higher antibody titers, but longer-term serological outcomes are unaffected by the anatomical localization of immunization.
人体临床试验报告称，同侧（同一侧）和对侧（另一侧）初免-加强疫苗接种的免疫结果可能存在差异。然而，我们对于保持或改变免疫解剖部位如何影响生发中心（GCs）和抗体反应的机制理解有限。在此，我们使用一种佐剂化的SARS-CoV-2刺突疫苗，剖析C57BL/6小鼠在同侧或对侧初免-加强疫苗接种后引流淋巴结中的GC动态和血清学结果。对侧接种在不同淋巴结引发独立的GCs，强大的二级GCs仅在二次远端接种时出现，而来自初次接种部位的持续GCs未得到增强。相比之下，同侧接种导致GC活动持续。同侧接种加速了针对原始株（野生型[WT]）、β株和BA.1株的抗体滴度的产生，但在28天之后，同侧和对侧组在抗体滴度、持久性和中和能力方面后期相当。使用异源SARS-CoV-2 WT/BA.1刺突初免-加强模型，产生了针对WT和BA.1刺突的交叉反应性GC反应，其血清学和GC动态与我们的同源模型类似。在交叉反应性GC B细胞内，观察到对WT和BA.1抗原的差异识别，并根据同侧或对侧接种方案在初级或二级GCs中进一步分区。总体而言，保持共同的初免-加强接种部位可增强记忆B细胞召回的动力学，并短暂驱动更高的抗体滴度，但长期血清学结果不受免疫解剖定位的影响。
