Nanovaccine Shows Promise in Reducing Plaque Formation in Mice

A research team from Nanjing University of Science and Technology is developing a preventive vaccine aimed at combating atherosclerosis, a chronic inflammatory condition characterized by lipid deposits in arterial walls. Their recent study, published in the journal Nature Communications, investigates the potential of immunological strategies to either prevent or treat this disease.

Atherosclerosis has been a focus of various therapeutic approaches, particularly those utilizing antibody and cell-based strategies to eliminate lipid-rich plaques. One of the key targets has been Apolipoprotein B (ApoB), found in low-density lipoproteins (LDL), which has been identified as a promising antigen for eliciting a protective immune response. Among the peptides derived from ApoB, the peptide p210 has emerged as a suitable candidate for atherosclerotic vaccines.

The researchers introduced a nanotechnology-based vaccine that incorporates the p210 antigen alongside an immunostimulatory adjuvant, CpG-oligodeoxynucleotide (CpG-ODN). These components were attached to superparamagnetic iron oxide nanoparticles (SPION) to optimize antigen presentation and effectively activate dendritic cells.

The characterization of these nanoparticles revealed a uniform particle size of approximately 15 nm, with hydrodynamic diameters around 58.6 nm. The targeted functional coating with the CpG-ODN adjuvant and p210 peptide significantly enhanced uptake by dendritic cells (DCs).

While CpG-ODN was predominantly taken up through the Scavenger Receptor A (SR-A), which mediates the uptake of oxidized lipoproteins, the p210 uptake occurred through macropinocytosis and mannose receptor-mediated pathways. This dual transport mechanism improved antigen cross-presentation and DC activation, as evidenced by increased expression of co-stimulatory molecules (CD86, CD80) and MHC class I and II molecules.

In vitro studies demonstrated that the nanovaccine cocktail enhanced cytokine release from dendritic cells, particularly IL-12p70, IL-6, and TNF-?, promoting a Th1-dominant immune response. Functional analyses in co-cultures of dendritic cells with murine splenocytes showed an increased expansion of CD8+ effector cells exhibiting pronounced effector/memory phenotypes. The vaccines also induced a significant IgM and IgG response against p210, which persisted over time.

The efficacy of the nanovaccine was further tested in an atherosclerosis mouse model (ApoE-/- mice), where three doses of the vaccine led to a significant reduction in atherosclerotic plaque development. The plaques observed in the aortas of treated mice were not only smaller but also exhibited improved stability characterized by increased collagen enrichment. Immunohistochemical analyses indicated reduced infiltration of macrophages and dendritic cells, along with decreased expression of the adhesion molecule ICAM-1, suggesting an attenuated inflammatory response.

Mechanistically, the nanovaccine modulated both CD4+ and CD8+ T cell populations, resulting in an overall decrease in pro-inflammatory T cell activity. Due to its formulation, the vaccine preferentially accumulated in lymphatic organs, minimizing non-specific organ distribution and potential side effects.

These findings indicate that the SPION-based nanovaccine approach could represent a promising strategy for preventive immunization against atherosclerosis. The combination of targeted antigen presentation, enhanced DC activation, and the induction of a protective humoral and cellular immune response may pave the way for new treatments for inflammatory cardiovascular diseases.