Improved biodistribution and enhanced immune response of subunit vaccine using a nanostructure formed by self-assembly of ascorbyl palmitate

• Published in: Nanomedicine Vol. 58; p. 102749
• Main Authors: Marin, Constanza, Ruiz Moreno, Federico N., Sánchez Vallecillo, María F., Pascual, María M., Dho, Nicolas D., Allemandi, Daniel A., Palma, Santiago D., Pistoresi-Palencia, María C., Crespo, María I., Gomez, Cesar G., Morón, Gabriel, Maletto, Belkys A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Adjuvant; Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacokinetics; Animals; Ascorbic Acid - analogs & derivatives; Coa-ASC16; CpG-ODN; Female; Interferon-gamma - metabolism; Mice; Mice, Inbred C57BL; Nanostructure; Nanostructures - chemistry; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - pharmacokinetics; Ovalbumin - chemistry; Ovalbumin - immunology; Tissue Distribution; Vaccine; Vaccines, Subunit - chemistry; Vaccines, Subunit - immunology; Vaccines, Subunit - pharmacokinetics; UMAP; LN; Vaccine; Nanostructure; ASC16; OCC; BMDCs; Coa-ASC16; OC; Ne; pDCs; CpG-ODN; Adjuvant; OVA; cDCs
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2024.102749

New adjuvant strategies are needed to improve protein-based subunit vaccine immunogenicity. We examined the potential to use nanostructure of 6-O-ascorbyl palmitate to formulate ovalbumin (OVA) protein and an oligodeoxynucleotide (CpG-ODN) (OCC). In mice immunized with a single dose, OCC elicited an OVA-specific immune response superior to OVA/CpG-ODN solution (OC). Rheological studies demonstrated OCC's self-assembling viscoelastic properties. Biodistribution studies indicated that OCC prolonged OVA and CpG-ODN retention at injection site and lymph nodes, reducing systemic spread. Flow-cytometry assays demonstrated that OCC promoted OVA and CpG-ODN co-uptake by Ly6ChiCD11bhiCD11c+ monocytes. OCC and OC induced early IFN-γ in lymph nodes, but OCC led to higher concentration. Conversely, mice immunized with OC showed higher serum IFN-γ concentration compared to those immunized with OCC. In mice immunized with OCC, NK1.1+ cells were the IFN-γ major producers, and IFN-γ was essential for OVA-specific IgG2c switching. These findings illustrate how this nanostructure improves vaccine's response. In a murine model, we explored a novel strategy for formulating vaccine components. The OVA antigen and the CpG-ODN immunostimulant were nanoformulated with a nanostructure formed by self-assembly of ascorbyl palmitate. In parallel, other mice were vaccinated with OVA and CpG-ODN formulated in an aqueous solution. The nanoformulation improved the biodistribution of the vaccine components, favoring their accumulation in the draining lymph node of the injection site over systemic circulation. This profoundly influenced on the overall immune response. Notably, mice vaccinated with the nanoformulation exhibited markedly superior antigen-specific immune responses when compared to those vaccinated with the soluble formulation. [Display omitted]