Mesoporous silicon microparticles enhance antiviral immunity and memory responses against SARS-CoV-2

Silica-based materials have attracted considerable interest as vaccine adjuvants due to their ability to potentiate immune responses. In this study, we evaluated the immunogenicity and protective efficacy of heteromorphous mesoporous silicon microparticles (MSMPs) as an adjuvant in the context of SARS-CoV-2 vaccination. MSMPs conjugated with the S1 subunit of the spike protein (MSMPs-S1) elicited a robust and sustained humoral immune response in BALB/c mice, comparable to that induced by aluminum-based adjuvants. Following a booster dose, MSMPs-S1 significantly increased IgG2a titers and neutralizing antibody levels, surpassing those observed with Al(OH)₃-based formulations. In addition, MSMPs-S1 enhanced cellular immunity, as reflected by higher IFN-γ production in T cells relative to the aluminum-adjuvanted group. In k18-hACE2 transgenic mice, vaccination with MSMPs-S1 conferred protection against a lethal SARS-CoV-2 challenge, resulting in marked reductions in viral loads in both lung and brain tissues. In vitro, stimulation of human peripheral blood mononuclear cells (PBMCs) with MSMPs-S1 increased IFN-γ production in T cells, particularly in the presence of dendritic cells. Collectively, these findings support the potential of MSMPs as an effective adjuvant capable of promoting both humoral and cellular immunity, with relevance for the development of vaccines targeting emerging viral pathogens.