Editorial: Nanoparticle-Based Delivery Systems on Immunomodulation

Pedro Augusto Carvalho Costa^1,2*Pedro Pires Goulart Guimarães^1,2

• ¹Federal University of Minas Gerais, Belo Horizonte, Brazil
• ²Department of Physiology and Biophysics, Institute of Biological Sciences, Belo Horizonte, Brazil

Hanna and co-authors described an intradermal injection of gold NPs (GNPs) loaded with the proinsulin peptide C19-A3 in type 1 diabetes patients leads to the recruitment and retention of immune cells in the skin, particularly clonally expanded Tcells with activated phenotypes (3). About half of these T-cells were found to be specific for either GNP or proinsulin. Gold-specific clones were all CD8+, while proinsulinspecific clones included both CD8+ and CD4+ cells, with CD8+ clones showing a cytotoxic phenotype marked by high levels of granulysin (GNLY) and KIR receptors. These antigen-specific T-cells persisted in the skin for months to years, exhibiting various memory phenotypes. The study suggests that the T-cell response, which targets both the gold core and the antigen, could enhance the formation of resident memory T-cells in response to vaccines. Furthermore, their scRNAseq data indicates that focusing on these expanded T-cells is an effective method for identifying antigen-specific cells, which could aid in monitoring the intradermal delivery of antigens and NPs for immune modulation in humans.Su and co-authors developed a vaccine against a major pathogen causing severe diarrhea and high mortality in newborn piglets using bacterium-like particles (BLPs) called S1-BLPs, which display the S1 protein from the Porcine epidemic diarrhea virus (PEDV) spike protein (4). The study examined how different vaccination routes affected immune responses in mice. Results showed that intramuscularly vaccinated mice had higher serum IgG levels compared to those vaccinated intranasally. However, intranasal vaccination led to the presence of specific IgA antibodies in both serum and intestinal fluid, which were absent in intramuscularly vaccinated mice. Additionally, intranasal administration increased cytokines IFN-γ and IL-4 levels in serum. The immune response from intramuscular injections indicated a stronger type 1 helper T (Th1) cell immunity. Overall, S1-BLPs can induce both systemic and local immune responses, with the route of administration influencing antibody types and Th responses. Intranasal S1-BLPs effectively stimulated secretory IgA in the intestinal mucosa, suggesting their potential as a mucosal vaccine against PEDV.Yin and co-authors developed an innovative virus-like nanoparticle (VLP) vaccine that simultaneously displayed Nipah virus (NiV) attachment glycoproteins (G) from NiV and related henipaviruses, leveraging the self-assembling characteristics of ferritin protein (5). When compared to the NiV G subunit vaccine, their NP vaccine generated significantly higher levels of neutralizing antibodies and offered complete protection against a lethal NiV infection in Syrian hamsters. Notably, the NPs vaccine prompted the production of antibodies that showed enhanced cross-reactivity to both related and unrelated henipaviruses. These results highlight the promising potential of ferritin-based NP vaccines in delivering broad-spectrum and long-lasting protection against Nipah virus and emerging zoonotic henipavirus threats.In a review paper, Adugna and co-authors described that vaccination remains the primary strategy to combat Japanese encephalitis (JE), with inactivated and live attenuated vaccines demonstrating strong immunogenicity (6). However, traditional vaccine production is costly and involves significant biosafety risks due to the extensive cultivation of pathogens, posing additional dangers for individuals with compromised immune systems. As a result, research has shifted toward NP platforms for developing next-generation JE vaccines. A systematic review analyzed 28 studies on NP-based JE vaccines published between 2000 and 2023, revealing that 57.14% focused on virus-like particles (VLPs) using structural proteins, while other studies employed sub-viral particles (SVPs), biopolymers, and synthetic or inorganic NPs. These vaccines consistently enhanced humoral and cellular immune responses, providing 70-100% protection against lethal JE virus challenges in mice. With further refinement, NP-based vaccines may offer promising solutions for immunizing humans and animals.Recent technological advances-particularly in nanoparticle (NP)-based delivery systems-have significantly accelerated the production of safe, targeted, and adaptable immunotherapies (7). NP-based technologies offer a compelling solution, enabling precision targeting, controlled release, and immune system modulation. Platforms such as mRNA, protein-based, and DNA technologies have successfully developed promising antiviral solutions (Figure 1 4) Nanoparticles escape the endosomal compartment. (5,6,7) pDNA is released into the cytoplasm, enters the nucleus and transcription of pDNA into mRNA occurs. (8) mRNA is translated into antigenic proteins in the cytoplasm. (9) Antigens are produced and presented to initiate an immune response.