Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide.
To assess the ability of gold nanoparticles (GNPs) to act as a size-dependent carrier, a synthetic peptide resembling foot-and-mouth disease virus (FMDV) protein was conjugated to GNPs ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). An extra cysteine was added to the C-terminus of the FMDV peptide (pFMDV) to ensure maximal conjugation to the GNPs, which have a high affinity for sulfhydryl groups. The resultant pFMDV-GNP conjugates were then injected into BALB/c mice. Immunization with pFMDV-keyhole limpet hemocyanin (pFMDV-KLH) conjugate was also performed as a control. Blood was obtained from the mice after 4, 6, 8, and 10 weeks and antibody titers against both pFMDV and the carriers were measured. For the pFMDV-GNP immunization, specific antibodies against the synthetic peptide were detected in the sera of mice injected with 2, 5, 8, 12, and 17 nm pFMDV-GNP conjugates. Maximal antibody binding was noted for GNPs of diameter 8-17 nm. The pFMDV-GNPs induced a three-fold increase in the antibody response compared to the response to pFMDV-KLH. However, sera from either immunized mouse group did not exhibit an antibody response to GNPs, while the sera from pFMDV-KLH-immunized mice presented high levels of binding activity against KLH. Additionally, the uptake of pFMDV-GNP in the spleen was examined by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscopy (TEM). The quantity of GNPs that accumulated in the spleen correlated to the magnitude of the immune response induced by pFMDV-GNP. In conclusion, we demonstrated the size-dependent immunogenic properties of pFMDV-GNP conjugates. Furthermore, we established that GNPs ranging from 8 to 17 nm in diameter may be ideal for eliciting a focused antibody response against a synthetic pFMDV peptide.
Chen
Yu-Shiun
YS
Department of Materials Science and Engineering, National Chiao Tung University, 1001 University Road, EE137, Hsinchu 300, Taiwan, Republic of China.
Hung
Yao-Ching
YC
Lin
Wei-Hsu
WH
Huang
Guewha Steven
GS
D000818:Animals; D000914:Antibodies, Viral; D000917:Antibody Formation / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D006046:Gold / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D007106:Immune Sera; D007114:Immunization; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010455:Peptides / Q000276:immunology*; D013056:Spectrophotometry, Ultraviolet; D013154:Spleen / Q000378:metabolism / Q000648:ultrastructure; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D004337:Drug Carriers; D007106:Immune Sera; D010455:Peptides; D014764:Viral Proteins; D014765:Viral Vaccines; D006046:Gold; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin