An investigation into the potential use of nanoparticles as adjuvants for the production of polyclonal antibodies to low molecular weight compounds

George, Suja E.; Elliott, Christopher T.; McLaughlin, Declan; Delahaut, Philippe; Akagi, Takami; Akashi, Mitsuru; Fodey, Terence L.

doi:10.1016/j.vetimm.2012.06.002

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…This finding has interesting applications for the routine production of antibodies with biotechnological and diagnostic purposes, because immunizations without classical adjuvants are much easier, cheaper, faster, and less painful 450 for animals. The contraindications and negative health effects of the adjuvants employed in animal experimentation, including FA, have been widely described, [67,83] and the painful consequences for the skin are also well known. In our experiments, rabbits showed no skin damage, no wounds, and no apparent negative reactions when subcutaneously injected with CNT constructs in buffer.…”

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confidence: 99%

“…In line with our results, excellent examples of the production of anti-hapten antibodies using different 455 nanoparticles as safe delivery vehicles have been recently reported for several low molecular weight chemicals. [67,68] No IgG response against azoxystrobin was observed in rabbits immunized with 3d + FA (without carrier protein) or with the 5 + 3b mixture (no covalent linking with the CNT). The absence of a response with 3d confirms the paradigm that a protein is required for the effective production of 460 anti-hapten antibodies.…”

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confidence: 99%

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

Parra

Abad‐Somovilla

Mercader

et al. 2013

Journal of Controlled Release

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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.

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confidence: 99%

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confidence: 99%

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

Parra

Abad‐Somovilla

Mercader

et al. 2013

Journal of Controlled Release

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“…Antibodies have been produced to bind the metabolites (Fig. 1), or derivatives of the metabolites, of the five major nitrofuran drugs: AOZ [5,[7][8][9][10], SEM [11][12][13][14][15], AMOZ [16][17][18][19][20], AHD [21][22][23][24][25] and DNSH [26]. The majority of publications focus on analysis of food products of animal origin in which these metabolites are the target analytes.…”

Section: Nitrofuran Haptens and Conjugatesmentioning

confidence: 99%

Development of Antibodies and Immunoassays for Monitoring of Nitrofuran Antibiotics in the Food Chain

Cooper

Fodey

Campbell

et al. 2018

COC

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Nitrofurans are a broad group of drugs once widely used for treatment of microbial and protozoal infections in many livestock species. However, as concerns grew globally with regard to the potentially carcinogenic and mutagenic effects of their residues in foods, they have been banned from use in many parts of the world. In order to monitor compliance to these bans it is essential to have fitfor-purpose testing methods. Immunoassays are the screening tool of choice for many testing laboratories due to their relative low cost, ease of use and high sensitivity. As is the case with all immunoassays, the most important reagents required are high quality, high affinity antibodies that exhibit the required sensitivity and specificity. Generating such antibodies for the nitrofuran family of compounds has required a great deal of effort in the design of immunogens, as the compounds, due to size, are not capable of eliciting an immune response in hosts and are not easily conjugated to carrier proteins. This article reviews the range of strategies used to successfully generate suitable antibodies to a wide range of these drugs and their metabolites. In addition, the platform technologies for nitrofuran detection have moved from simple enzyme-linked immunosorbent assay (ELISA)-based procedures to more sophisticated multiplexing systems which can undertake faster and broader spectrum testing for the parent drugs and their metabolites. Reviews of the technologies used for immunochemical detection of the nitrofurans and of commercially available test kits are also presented.

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“…TiterMax™, Ribi™, and Gerbu™ adjuvants) have been invented to generate a potent immune response with significantly reduced toxicity (Stils, 2005;Algate et al, 2013), but most of the evaluation studies were focused on developing antibodies to macromolecules. Only a few investigations have been carried out to find replacements for Freund's adjuvants in the production of hapten-specific antibodies (Erhard et al, 1991;Fodey et al, 2008;George et al, 2012;Maquieira et al, 2012;Parra et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a water-soluble adjuvant for the development of monoclonal antibodies against small-molecule compounds

Liu

Lan

et al. 2016

J. Zhejiang Univ. Sci. B

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A water-soluble adjuvant named QuickAntibody (QA) was introduced into the procedure of mouse immunization for the development of hapten-specific monoclonal antibodies (mAbs), using four kinds of pesticides as model compounds. Compared with conventional Freund's adjuvants, QA treatments offered relatively low but acceptable antiserum titers after three inoculations, gave little adverse effects to the experimental animals, and were preferable in harvesting splenocytes during the steps of cell fusion. Afterwards, hybridomas from the QA group were prepared and screened by both non-competitive and competitive indirect enzyme-linked immunosorbent assays (ELISAs). The efficiency of gaining immune-positive hybridomas was satisfactory, and the resultant mAbs showed sensitivities (half maximal inhibitory concentration (IC 50)) of 0.91, 2.46, 3.72, and 6.22 ng/ml to triazophos, parathion, chlorpyrifos, and fenpropathrin, respectively. Additionally, the performance of QA adjuvant was further confirmed by acquiring a high-affinity mAb against okadaic acid (IC 50 of 0.36 ng/ml) after three immunizations. These newly developed mAbs showed similar or even better sensitivities compared with previously reported mAbs specific to the corresponding analytes. This study suggested that the easy-to-use adjuvant could be applicable to the efficient generation of highly sensitive mAbs against small compounds.

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An investigation into the potential use of nanoparticles as adjuvants for the production of polyclonal antibodies to low molecular weight compounds

Cited by 6 publications

References 23 publications

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

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

Development of Antibodies and Immunoassays for Monitoring of Nitrofuran Antibiotics in the Food Chain

Evaluation of a water-soluble adjuvant for the development of monoclonal antibodies against small-molecule compounds

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