Periodic Mesoporous Organosilica as a Nanoadjuvant for Subunit Vaccines Elicits Potent Antigen-Specific Germinal Center Responses by Activating Naive B Cells.
Fangshen LiXinyao FengJiaxing HuangMo ZhangWenmo LiuXupu WangRui ZhuXun WangPengfei WangBin YuWei LiZhen-An QiaoXianghui YuPublished in: ACS nano (2023)
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.
Keyphrases
- immune response
- dendritic cells
- sars cov
- signaling pathway
- regulatory t cells
- hiv infected
- induced apoptosis
- antiretroviral therapy
- lymph node
- toll like receptor
- pi k akt
- respiratory syndrome coronavirus
- human immunodeficiency virus
- coronavirus disease
- hiv positive
- gram negative
- hepatitis c virus
- escherichia coli
- epithelial mesenchymal transition
- metal organic framework
- antimicrobial resistance
- type diabetes
- cell therapy
- hiv aids
- protein kinase
- mesenchymal stem cells
- endoplasmic reticulum stress
- inflammatory response
- early stage
- dna methylation
- south africa
- amino acid
- mass spectrometry
- high resolution
- cell free
- multidrug resistant
- gene expression
- transcription factor