Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing theantibody response against synthetic foot-and-mouth disease virus peptide

Abstract

To assess the ability of gold nanoparticles (GNPs) to act as a size-dependent carrier, asynthetic peptide resembling foot-and-mouth disease virus (FMDV) protein was conjugatedto GNPs ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). An extracysteine was added to the C-terminus of the FMDV peptide (pFMDV) to ensure maximalconjugation to the GNPs, which have a high affinity for sulfhydryl groups. The resultantpFMDV–GNP conjugates were then injected into BALB/c mice. Immunization withpFMDV–keyhole limpet hemocyanin (pFMDV–KLH) conjugate was also performed as acontrol. Blood was obtained from the mice after 4, 6, 8, and 10 weeks and antibody titersagainst both pFMDV and the carriers were measured. For the pFMDV–GNPimmunization, specific antibodies against the synthetic peptide were detected in the sera ofmice injected with 2, 5, 8, 12, and 17 nm pFMDV–GNP conjugates. Maximalantibody binding was noted for GNPs of diameter 8–17 nm. The pFMDV–GNPsinduced a three-fold increase in the antibody response compared to the response topFMDV–KLH. However, sera from either immunized mouse group did not exhibitan antibody response to GNPs, while the sera from pFMDV–KLH-immunizedmice presented high levels of binding activity against KLH. Additionally, theuptake of pFMDV–GNP in the spleen was examined by inductively coupled plasmamass spectroscopy (ICP-MS) and transmission electron microscopy (TEM). Thequantity of GNPs that accumulated in the spleen correlated to the magnitude of theimmune response induced by pFMDV–GNP. In conclusion, we demonstrated thesize-dependent immunogenic properties of pFMDV–GNP conjugates. Furthermore,we established that GNPs ranging from 8 to 17 nm in diameter may be idealfor eliciting a focused antibody response against a synthetic pFMDV peptide.