International Journal of Nanomedicine (Jul 2017)
Nanoparticle orientationally displayed antigen epitopes improve neutralizing antibody level in a model of porcine circovirus type 2
Abstract
Peiyang Ding,1,2 Teng Zhang,2,3 Yafei Li,1,2 Man Teng,2 Yaning Sun,2 Xiao Liu,2,4 Shujun Chai,2 Enmin Zhou,1 Qianyue Jin,2,5 Gaiping Zhang1,2,4,5 1College of Veterinary Medicine, Northwest A&F University, Yangling, 2Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, 3College of Life Sciences, Henan Agricultural University, 4College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, 5Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People’s Republic of China Abstract: Recent advancements in biotechnology have enabled the rapid identification and subsequent expression of pathogenic microbial major antigens that induce protective immune responses. However, subunit vaccines have not been successfully commercialized mainly due to the lack of sufficient levels of neutralizing antibodies (NAs). High levels of NA rely on the efficient recognition and cross-linking of multiple neutralizing epitopes with B-cell receptors (BCRs). Nanoparticles are able to display coupled antigenic arrays at high density and provide multiple binding molecular scenarios with BCRs. The high-resolution antigenic structure makes it possible to accurately display stable neutralizing epitopes. Therefore, the development of a nanovaccine that orientationally displays neutralizing epitopes is a feasible strategy. To address this hypothesis, the capsid (Cap) protein of porcine circovirus type 2 as model antigen was conjugated to gold nanoparticles (AuNPs) through direct reaction of the mercapto group of the unique cysteines with AuNPs, rendering Cap-AuNPs to have neutralizing epitopes on outer surface and an immunodominant epitope buried within the inner surface. In vitro studies showed that AuNPs promoted the phagocytosis of Cap protein and NA levels were significantly improved, meanwhile antibody levels against the immunodominant epitope was significantly reduced. In mouse studies, Cap-AuNP-immunized mice displayed a high production of interleukin (IL)-4, IL-10, and interferon-γ, suggesting that Cap-AuNPs can effectively activate CD4+ and CD8+ T cells and balance Th1 and Th2 cellular responses. This study presents a new vaccine design strategy based on antigen structure, where nanoparticles are coupled to antigens in well-ordered arrays and orientationally display neutralizing epitopes to enhance NA levels. Keywords: gold nanoparticles, porcine circovirus type 2, neutralizing antibody, epitopes, structure, orientationally display
