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Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium

Shruti Bakshi, Raquel Sanz García, Hans Van Der Weken (UGent) , Ashuwini Tharad (UGent) , Shubham Pandey (UGent) , Paloma Juarez Ortega, Vikram Virdi (UGent) , Bert Devriendt (UGent) , Eric Cox (UGent) and Anna Depicker (UGent)
(2020) JOURNAL OF CONTROLLED RELEASE. 321. p.416-429
Author
Organization
Abstract
Targeting a vaccine to the mucosal surface has recently been recognized as a promising approach to efficiently induce mucosal immune responses against enteric pathogens. However, poor uptake and inefficient transport of orally delivered subunit vaccines across the intestinal epithelium combined with weak immune responses still present important bottlenecks for mucosal vaccination. A possible strategy suggested to surmount these hurdles is to target the selected antigen to transcytotic receptors, such as aminopeptidase N (APN) present on enterocytes and antigen-presenting cells (APCs). Therefore, we aimed to identify potent and selective VHHs against porcine aminopeptidase N (pAPN), that were fused to the fragment crystallizable (Fc) domain of the murine IgG2a, resulting in dimeric VHH-MG fusions. Out of a library of 30 VHH-MG fusion candidates, two fusions displaying the best binding on pAPN-expressing cells were selected and showed in vivo internalization across the porcine gut epithelium. One of these fusions triggered systemic and intestinal IgA responses upon oral administration. Our results demonstrate the potential of bivalent VHH-MG fusions as delivery vehicles for vaccine antigens. VHH-mediated and APN-targeted antigens to generate protective immunity at the mucosal surface remains to be further validated.
Keywords
Antibody Engineering, VHH-Fc, VHH, Nanobodies, Single-domain Antibodies, Protein Expression, Production, Recombinant Antibody, Nanobody Characterization, Library Screening, Bioxp, Gibson Cloning, Vaccine Targeting, Intestinal Infection, Escherichia-coli, Antigen Delivery, Nanobodies, Expression, Generation, Receptor, Therapeutics, Proteins, Fimbriae, Affinity

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MLA
Bakshi, Shruti, et al. “Evaluating Single-Domain Antibodies as Carriers for Targeted Vaccine Delivery to the Small Intestinal Epithelium.” JOURNAL OF CONTROLLED RELEASE, vol. 321, 2020, pp. 416–29, doi:10.1016/j.jconrel.2020.01.033.
APA
Bakshi, S., Sanz García, R., Van Der Weken, H., Tharad, A., Pandey, S., Juarez Ortega, P., … Depicker, A. (2020). Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium. JOURNAL OF CONTROLLED RELEASE, 321, 416–429. https://doi.org/10.1016/j.jconrel.2020.01.033
Chicago author-date
Bakshi, Shruti, Raquel Sanz García, Hans Van Der Weken, Ashuwini Tharad, Shubham Pandey, Paloma Juarez Ortega, Vikram Virdi, Bert Devriendt, Eric Cox, and Anna Depicker. 2020. “Evaluating Single-Domain Antibodies as Carriers for Targeted Vaccine Delivery to the Small Intestinal Epithelium.” JOURNAL OF CONTROLLED RELEASE 321: 416–29. https://doi.org/10.1016/j.jconrel.2020.01.033.
Chicago author-date (all authors)
Bakshi, Shruti, Raquel Sanz García, Hans Van Der Weken, Ashuwini Tharad, Shubham Pandey, Paloma Juarez Ortega, Vikram Virdi, Bert Devriendt, Eric Cox, and Anna Depicker. 2020. “Evaluating Single-Domain Antibodies as Carriers for Targeted Vaccine Delivery to the Small Intestinal Epithelium.” JOURNAL OF CONTROLLED RELEASE 321: 416–429. doi:10.1016/j.jconrel.2020.01.033.
Vancouver
1.
Bakshi S, Sanz García R, Van Der Weken H, Tharad A, Pandey S, Juarez Ortega P, et al. Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium. JOURNAL OF CONTROLLED RELEASE. 2020;321:416–29.
IEEE
[1]
S. Bakshi et al., “Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium,” JOURNAL OF CONTROLLED RELEASE, vol. 321, pp. 416–429, 2020.
@article{8648310,
  abstract     = {{Targeting a vaccine to the mucosal surface has recently been recognized as a promising approach to efficiently induce mucosal immune responses against enteric pathogens. However, poor uptake and inefficient transport of orally delivered subunit vaccines across the intestinal epithelium combined with weak immune responses still present important bottlenecks for mucosal vaccination. A possible strategy suggested to surmount these hurdles is to target the selected antigen to transcytotic receptors, such as aminopeptidase N (APN) present on enterocytes and antigen-presenting cells (APCs). Therefore, we aimed to identify potent and selective VHHs against porcine aminopeptidase N (pAPN), that were fused to the fragment crystallizable (Fc) domain of the murine IgG2a, resulting in dimeric VHH-MG fusions. Out of a library of 30 VHH-MG fusion candidates, two fusions displaying the best binding on pAPN-expressing cells were selected and showed in vivo internalization across the porcine gut epithelium. One of these fusions triggered systemic and intestinal IgA responses upon oral administration. Our results demonstrate the potential of bivalent VHH-MG fusions as delivery vehicles for vaccine antigens. VHH-mediated and APN-targeted antigens to generate protective immunity at the mucosal surface remains to be further validated.}},
  author       = {{Bakshi, Shruti and Sanz García, Raquel and Van Der Weken, Hans and Tharad, Ashuwini and Pandey, Shubham and Juarez Ortega, Paloma and Virdi, Vikram and Devriendt, Bert and Cox, Eric and Depicker, Anna}},
  issn         = {{0168-3659}},
  journal      = {{JOURNAL OF CONTROLLED RELEASE}},
  keywords     = {{Antibody Engineering,VHH-Fc,VHH,Nanobodies,Single-domain Antibodies,Protein Expression,Production,Recombinant Antibody,Nanobody Characterization,Library Screening,Bioxp,Gibson Cloning,Vaccine Targeting,Intestinal Infection,Escherichia-coli,Antigen Delivery,Nanobodies,Expression,Generation,Receptor,Therapeutics,Proteins,Fimbriae,Affinity}},
  language     = {{eng}},
  pages        = {{416--429}},
  title        = {{Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium}},
  url          = {{http://doi.org/10.1016/j.jconrel.2020.01.033}},
  volume       = {{321}},
  year         = {{2020}},
}
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