Periodic Mesoporous Organosilica as a Nanoadjuvant for Subunit Vaccines Elicits Potent Antigen-Specific Germinal Center Responses by Activating Naive B Cells

Abstract

Infection diseases such as AIDS and COVID-19 remain challenging in regard to protective vaccine design, while adjuvants are critical for subunit vaccines to induce strong, broad, and durable immune responses against variable pathogens. Here, we demonstrate that periodic mesoporous organosilica (PMO) acts as a multifunctional nanoadjuvant by adsorbing recombinant protein antigens. It can effectively deliver antigens to lymph nodes (LNs), prolong antigen exposure, and rapidly elicit germinal center (GC) responses by directly activating naive B cells via the C-type lectin receptor signaling pathway. In mice, both the gp120 trimer (HIV-1 antigen) and the receptor-binding domain (SARS-CoV-2 antigen) with the PMO nanoadjuvant elicit potent and durable antibodies that neutralize heterologous virus strains. LN immune cells analysis shows that PMO helps to effectively activate the T-follicular helper cells, GC B cells, and memory B cells and eventually develop broad and durable humoral responses. Moreover, the PMO nanoadjuvant elicits a strong cellular immune response and shapes this immune response by eliciting high levels of effector T helper cell cytokines. This study identifies a promising nanoadjuvant for subunit vaccines against multiple pathogens.

The Fourth Symposium of Grand Challenges on HIV (2023.12.28)

“…By exploring several immunogenicity enhancement strategies, including novel nanoparticle adjuvants, nanoparticle vaccine design and optimization, and virus vector vaccines, immunization with the gp120 trimer immunogen induced highly effective and broad-spectrum neutralizing antibodies through mechanisms such as enhancing germinal center responses and activating cellular immune reactions. [11] Caijun Sun (Sun Yat-Sen University) presented a novel therapeutic HIV vaccine strategy using optimized HSV vectors. The recombinant vectors could elicit strong HIV antigen-specific humoral and cellular immune responses in mice.…”

“…By exploring several immunogenicity enhancement strategies, including novel nanoparticle adjuvants, nanoparticle vaccine design and optimization, and virus vector vaccines, immunization with the gp120 trimer immunogen induced highly effective and broad-spectrum neutralizing antibodies through mechanisms such as enhancing germinal center responses and activating cellular immune reactions. [11]…”