Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

Chattopadhyay, Saborni; Chen, Jui-Yi; Chen, Hui-Wen; Hu, Che-Ming Jack

Thiol and amine groups on protein or peptide antigens are frequently exploited for bioconjugation with nanoparticles. The thiol group on a cysteine amino acid is a powerful nucleophile with the capacity to form covalent linkage. Several linker groups, such as maleimide and succinimidyl 3-(2-pyridyldithio)propionate (SPDP), facilitate the conjugation between thiol-containing antigens with nanoparticles [183] . In a maleimide-thiol reaction, the nucleophilic thiolate anion attacks the π-bond of maleimide, forming the enolate intermediate and yielding the desired conjugate. This technique has been widely used to assemble nanoparticle vaccines [184] [185] [186] . In a study on refining a liposomal formulation of HIV vaccine, thiol chemistry was exploited to control the physiological conformation and density of the target antigen to modulate immune responses [186] . Thiols groups also readily associate with gold surfaces. The strong interaction between sulfur and gold drives the sulfur atom to fill the free orbitals of a gold atom, creating a coordinate covalent bond [187, 188] . Such approach has been extensively applied to associate nucleic acids [188] [189] [190] [191] [192] and antigens [193, 194] with gold nanoparticles.