The Immunoenhancement Effects of Polyethylenimine-Modified Chinese Yam Polysaccharide-Encapsulated PLGA Nanoparticles as an Adjuvant

Abstract

Yue Zhang,1,2 Pengfei Gu,1,2 Adelijiang Wusiman,1,2 Shuwen Xu,1,2 Haiyu Ni,1,2 Tianxin Qiu,1,2 Zhenguang Liu,1,2 Yuanliang Hu,1,2 Jiaguo Liu,1,2 Deyun Wang1,2 1Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing, People’s Republic of China; 2MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, People’s Republic of ChinaCorrespondence: Deyun Wang Tel [phone]Fax [phone]Email [email protected]: Poly(lactic-co-glycolic acid) (PLGA) has been extensively applied for sustained drug delivery and vaccine delivery system. However, vaccines delivered by PLGA nanoparticles alone could not effectively activate antigen-presenting cells (APCs) to induce strong immune responses.Purpose: The aim of the present study was to design polyethylenimine (PEI)-modified Chinese yam polysaccharide (CYP)-encapsulated PLGA nanoparticles (CYPP-PEI) as a vaccine delivery system and evaluate the adjuvant activities in vitro and in vivo.Materials and Methods: Cationic-modified nanoparticles exhibited high antigen absorption and could be efficiently taken by APCs to enhance the immune responses. Therefore, PEI-modified CYP-encapsulated PLGA nanoparticles (CYPP-PEI) were prepared. The storage stability and effective adsorption capacity for porcine circovirus-2 (PCV-2) antigen of these antigen-absorbed nanoparticles were measured for one month. Furthermore, the adjuvant activity of CYPP-PEI nanoparticles was evaluated on macrophages in vitro and through immune responses triggered by PCV-2 antigen in vivo.Results: The PCV-2 absorbed CYPP-PEI nanoparticles showed excellent storage stability and high absorption efficiency of PCV-2 antigen. In vitro, CYPP-PEI nanoparticles promoted antigen uptake, enhanced surface molecular expressions of CD80 and CD86, and improved cytokine secretion of TNF-α, IFN-γ, and IL-12p70 in macrophages. After immunization with CYPP-PEI/PCV-2 formulation in mice, the expressions of surface activation markers on dendritic cells which located in draining lymph nodes were increased, such as MHCI, MHCII, and CD80. In addition, CYPP-PEI nanoparticles induced dramatically high PCV-2-specific IgG levels which could last for a long time and stimulated the secretion of subtype antibodies and cytokines. The results showed that CYPP-PEI could induce Th1/Th2 mixed but Th1-biased type immune responses.Conclusion: Polyethylenimine-modified Chinese yam polysaccharide-encapsulated PLGA nanoparticle was a potential vaccine delivery system to trigger strong and persistent immune responses.Keywords: Chinese yam polysaccharide, polyethylenimine, poly(lactic-co-glycolic acid), nanoparticles, macrophages, immune response

Keywords

• chinese yam polysaccharides
• polyethylenimine；poly(lactic-co-glycolic acid)
• nanoparticles
• macrophages
• immune response