Rodrigues, K.A., et al. Vaccines combining slow release and follicle targeting of antigens increase germinal center B cell diversity and clonal expansion.

Rodrigues, K.A., et al. Vaccines combining slow release and follicle targeting of antigens increase germinal center B cell diversity and clonal expansion. Sci Transl Med, 2025 Jun 18, 17(803):eadw7499. PMID: 40531969

• This study explores an innovative vaccine strategy that leverages the combination of two key mechanisms: slow antigen release achieved through the use of alum-pSer anchoring, which helps retain the antigen within lymph nodes over an extended period, and the inclusion of a powerful saponin/TLR agonist adjuvant known as SMNP, which stimulates robust immune activation. By integrating these approaches, at a smart way, the researchers aim to improve the delivery, persistence, and presentation of the vaccine antigen to the immune system, thereby promoting stronger and more durable humoral immune responses.
• Using an HIV Env trimer in mice, the researchers demonstrated that this synergistic formulation promotes sustained antigen presence in B cell follicles and on follicular dendritic cells (FDCs), leading to improved germinal center responses characterized by increased diversity, clonal expansion of B cells, higher numbers of memory B cells and antibody-secreting cells, and stronger antibody production (serum IgG titers). 
• The saponin component plays several critical roles in enhancing the vaccine response as described in the study: A) promoting lymph flow and antigen trafficking, B) triggering inflammatory cytokines, C) enhancing antigen retention and presentation, D) amplifying the humoral immune response. The combination of slow antigen release and saponin adjuvant properties leads to increased germinal center B cell proliferation, diversified BCR repertoire, and higher serum antibody titers. It also promotes better recruitment of B cell clones and helps in developing more broadly neutralizing responses. 
• Combining slow-release antigen delivery with follicle-targeting adjuvants, such as alum-pSer and SMNP, enhances antigen retention in B cell follicles, diversifies the germinal center response, and improves humoral immunity. This strategy offers a promising approach to creating more effective vaccines by promoting sustained antigen availability and diverse B cell activation, especially against complex pathogens like HIV.

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