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<p>Germinal centers (GCs) are a complex and important aspect of humoral immunity. How GCs deal with changing antigens remains unclear, yet this biology could be central to next-generation vaccine strategies such as germline targeting. Here we demonstrate, in a mouse model with human immunodeficiency virus envelope surface protein immunogens, that rapid delivery of homologous or heterologous boosts results in highly positive outcomes. Rapid reimmunization expands on-target GC B cell (B<sub>GC</sub>) populations, which emerge almost exclusively from existing B<sub>GC</sub> cells. Early homologous boosting avoids prohibitive antibody titers and utilizes off-target antibodies to maximize the B<sub>GC</sub> response. Heterologous rapid boosting shifts affinity maturation towards the new antigen. The ‘refueled’ GCs are sustained, developing large affinity gains and evolving rapidly to bind wildtype HIV Env trimer within 56 days, even when using as few as two distinct antigens. These findings provide insights into GC biology and translatable paths to leveraging accelerated GC function.</p>

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Rapid boosting increases germinal center responses to sequential vaccines

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Sonya Haupt,
  • Christopher A. Cottrell,
  • Xiaoya Zhou,
  • Jeong Hyun Lee,
  • Alessia Liguori,
  • Nushin Alavi,
  • Danny Lu,
  • Nicole Phelps,
  • Diana Goodwin,
  • Elana Ben-Akiva,
  • Agnes A. Walsh,
  • Darrell J. Irvine,
  • William R. Schief,
  • Shane Crotty

摘要

Germinal centers (GCs) are a complex and important aspect of humoral immunity. How GCs deal with changing antigens remains unclear, yet this biology could be central to next-generation vaccine strategies such as germline targeting. Here we demonstrate, in a mouse model with human immunodeficiency virus envelope surface protein immunogens, that rapid delivery of homologous or heterologous boosts results in highly positive outcomes. Rapid reimmunization expands on-target GC B cell (BGC) populations, which emerge almost exclusively from existing BGC cells. Early homologous boosting avoids prohibitive antibody titers and utilizes off-target antibodies to maximize the BGC response. Heterologous rapid boosting shifts affinity maturation towards the new antigen. The ‘refueled’ GCs are sustained, developing large affinity gains and evolving rapidly to bind wildtype HIV Env trimer within 56 days, even when using as few as two distinct antigens. These findings provide insights into GC biology and translatable paths to leveraging accelerated GC function.