Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody–hapten complex: Rapid and robust IgG response induced by a single subcutaneous injection

Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D.; Chou, Wen-Ko; Farnell, Morgan B.; Mwangi, Waithaka; Berghman, Luc

doi:10.1016/j.jim.2012.02.006

Cited by 10 publications

(5 citation statements)

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“…A single dose of this vaccine was shown to be sufficient to elicit a strong antibody response in chickens as early as fourteen days after priming 10 . Furthermore, targeting a synthetic peptide antigen to chicken CD40 receptor showed accelerated and enhanced antibody responses against the peptide antigen compared to untargeted peptide 11 . PRRagonist-based targeting has also been investigated in chickens before.…”

Section: Introductionmentioning

confidence: 99%

Selectively targeting haemagglutinin antigen to chicken CD83 receptor induces faster and stronger immunity against avian influenza

et al. 2021

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The immunogenicity and protective efficacy of vaccines can be enhanced by the selective delivery of antigens to the antigen-presenting cells (APCs). In this study, H9N2 avian influenza virus haemagglutinin (HA) antigen, was targeted by fusing it to single-chain fragment variable (scFv) antibodies specific to CD83 receptor expressed on chicken APCs. We observed an increased level of IFNγ, IL6, IL1β, IL4, and CxCLi2 mRNA upon stimulation of chicken splenocytes ex vivo by CD83 scFv targeted H9HA. In addition, CD83 scFv targeted H9HA induced higher serum haemagglutinin inhibition activity and virus neutralising antibodies compared to untargeted H9HA, with induction of antibodies as early as day 6 post primary vaccination. Furthermore, chickens vaccinated with CD83 scFv targeted H9HA showed reduced H9N2 challenge virus shedding compared to untargeted H9HA. These results suggest that targeting antigens to CD83 receptors could improve the efficacy of poultry vaccines.

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Section: Introductionmentioning

confidence: 99%

Selectively targeting haemagglutinin antigen to chicken CD83 receptor induces faster and stronger immunity against avian influenza

et al. 2021

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“…Only consecutive linear regions of the alpha-toxin were selected for synthesis to avoid the time and expense associated with the protein expression and purification required to produce conformational epitopes. Biotinylated commercially synthesized peptides (Genscript, Piscataway, NJ, USA) were incorporated stoichiometrically in the antibody-guided immunization complex as described previously (5). …”

Section: Methodsmentioning

confidence: 99%

“…Immunization complexes were produced as previously described by Chen et al (5). Biotinylated CD40-targeting antibodies were complexed with each synthetic peptide using streptavidin as a scaffold.…”

Section: Methodsmentioning

confidence: 99%

“…These CD40-targeting antibody-guided complexes have previously been tested for use as in vivo delivery systems for vaccines (2–4). In poultry, this CD40-targeting approach has been shown to induce robust and specific IgG serum antibody responses within 1 week (5), as well as sIgA production in the mucosal samples (6), essentially bypassing the weaker, chiefly IgM, initial immune response associated with primary immunizations. The application of this guided complex to induce rapid antibody production beyond its initial vaccine designation has not been exploited.…”

Section: Introductionmentioning

confidence: 99%

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A Fast and Inexpensive Protocol for Empirical Verification of Neutralizing Epitopes in Microbial Toxins and Enzymes

et al. 2017

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In vivo targeting of peptides to antigen-presenting cells by use of agonistic anti-CD40 monoclonal antibodies has been used successfully as an immune response enhancing strategy. When tested in chickens, the antibody-guided platform was capable of inducing specific IgG production within 1 week postimmunization. However, use of this method beyond its initial conception as a vaccine delivery tool has not been fully exploited. In this study, Clostridium perfringens alpha-toxin was used as a model microbial toxin for epitope mapping by using the antibody-guided immunization method to generate a panel of antibodies against specific, regions of the toxin in an attempt to identify crucial determinants on the toxin which, once bound, would hinder downstream toxicity. Alpha-toxin, which possesses both hemolytic and phospholipase C (PLC) enzymatic activities, has long been known to be one of the key destructive etiological agents of necrotic enteritis disease in poultry. Previous attempts to identify crucial antigenic determinants on the toxin mediating its enzymatic activities have been performed using expensive and labor-intensive site-directed mutagenesis techniques. To create a panel of antibodies, 23 short candidate alpha-toxin peptide regions were selected in silico using B-cell epitope prediction algorithms in the public domain and were custom synthesized to load onto the antibody-guided complex for immunization in birds for antisera production. Peptide-specific antibody responses were generated against all candidate neutralizing epitopes and used for in vitro toxin neutralization tests. Antisera against all 23 peptides were able to neutralize the toxin’s hemolytic activity, with neutralization titers ranging from 80 to 320, but none were effective in blocking PLC. The novel approach of antibody-guided immunization introduces a new, inexpensive method for polyclonal IgG production and de facto identification of neutralizing epitopes in microbial toxins and enzymes within 2 weeks from in silico analysis of a putative target sequence.

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“…In recent studies, our group demonstrated a novel anti-chCD40 mAb (designated mAb 2C5) has the ability to induce significant stimulation in chicken HD11 macrophage cell line. When this CD40 agonist was administered using different routes in combination with a desired antigenic peptide, the CD40-targeted immunogen induced robust immune response and several desired effects such as immunoglobulin class switching occured [17][18][19] . However, the high cost and difficulty for mAb production would make it impractical to commercialize this as a vaccine adjuvant.…”

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confidence: 99%

DNA aptamer-based rolling circle amplification product as a novel immunological adjuvant

Al-Ogaili

Liyanage

Lay

et al. 2020

Sci Rep

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Several agonists to CD40 have shown to induce acquired immune responses. Here, we developed and evaluated the rolling circle amplification (RCA) products that are based on anti-CD40 DNA aptamers as a novel vaccine adjuvant. First, we developed DNA aptamers with specific binding affinity to chicken CD40 extra domain (chCD40ED). Next, we prepared the RCA products that consist of these aptamers to increase the spanning space and overall binding affinity to chCD40ED. Using 8 DNA aptamer candidates, 4 aptamer-based RCA products (aptamer RCAs) were generated, each consisting of two distinct aptamers. We demonstrated that all 4 aptamer RCAs significantly induced the signal transduction in chicken HD11 macrophage cell line (p < 0.05). Finally, we conjugated one of the aptamer RCAs (Aptamer RCA II) to M2e epitope peptide of influenza virus as a model hapten, and the immune complex was injected to chickens. Aptamer RCA II stimulated anti-M2e IgG antibody production to the level significantly higher as compared to the control (M2e epitope alone; p < 0.05). The results of our work suggest that aptamer RCA is a novel platform to boost the efficacy of vaccines, which might find broad applications to other antigens beyond M2e epitope evaluated in this study using chicken infection model.

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Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody–hapten complex: Rapid and robust IgG response induced by a single subcutaneous injection

Cited by 10 publications

References 9 publications

Selectively targeting haemagglutinin antigen to chicken CD83 receptor induces faster and stronger immunity against avian influenza

Selectively targeting haemagglutinin antigen to chicken CD83 receptor induces faster and stronger immunity against avian influenza

A Fast and Inexpensive Protocol for Empirical Verification of Neutralizing Epitopes in Microbial Toxins and Enzymes

DNA aptamer-based rolling circle amplification product as a novel immunological adjuvant

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