Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens

Abstract

Carbon nanotubes (CNTs) are nanomaterials with interesting emerging applications. Their 25 properties makes CNTs excellent candidates for use as new nanovehicles in drug delivery, immunization and diagnostics. In the current study, we assessed the immune-response-amplifying properties of CNTs to haptens by using azoxystrobin, the first developed strobilurin fungicide, as a model analyte. An azoxystrobin derivative bearing a carboxylated spacer arm (hapten AZc6) was covalently coupled to bovine serum albumin (BSA), and the resulting BSA-AZc6 conjugate was 30 covalently linked to four functionalized CNTs of different shapes and sizes, varying in diameter and length. These four types of CNT-based constructs were obtained using efficient, fast, and easy functionalization procedures based on microwave-assisted chemistry. New Zealand rabbits and BALB/c mice were immunized with BSA-AZc6 alone and with the four CNT-BSA-AZc6 constructs, both with and without Freund's adjuvant. The IgG-type antibody responses were assessed 35 in terms of the titer and affinity, paying special attention to the relationship between the immune response and the size and shape of the employed CNTs. Immunization with CNT-BSA-AZc6 resulted in enhanced titers and excellent affinities for azoxystrobin. More important, remarkable IgG responses were obtained even in the absence of an adjuvant, thus proving the self-adjuvanting capability of CNTs. Immunogens were able to produce strong anti-azoxystrobin immune responses 40 in rabbits even when administered at a BSA-AZc6 conjugate dose as low as 0.05 g. The short and thick CNT-BSA-AZc6 construct produced the best antibody response under all tested conditions.

Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization

“…[9, 28] Meanwhile, conjugating protein antigen to the surface of NPs could promote its delivery and presentation. [29, 30] In our previous nanovaccine design, hapten was conjugated to the surface of protein antigens. [26] As the localization of haptens on vaccine NPs may potentially affect the recognition of antigens by immune cells, in this current work, we rationalized the design of a hybrid NP-based nicotine vaccine by studying the impact of hapten localization on its immunogenicity and pharmacokinetic efficacy.…”

Novel approaches for the design, delivery and administration of vaccine technologies

“…Carbon nanoparticles have also been studied extensively for drug and vaccine delivery [76]. They can be synthesized into a variety of different nanotubes and mesoporous spheres [107,108]. Carbon nanotubes are potentially capable of carrying multiple antigens and are rapidly taken up by antigen-presenting cells [109].…”

Targeting Pattern Recognition Receptors (PRRs) in Nano- Adjuvants: Current Perspectives

“…There are a number of features that make CNTs an attractive candidate material for a wide range of studies,including drug delivery [70,71], vaccine and adjuvant delivery [67,72,75,76], DNA and protein biosensing [75], and highly specific detection of autoantibodies in human autoimmune diseases [76]. CNTs are almost chemically inert and non-immunogenic [74,77].…”