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Antigen-adjuvant nanoconjugates for nasal vaccination: an improvement over the use of nanoparticles?
Mol Pharm. 2010 Dec 06; 7(6):2207-15.MP

Abstract

Entrapment of antigens in mucoadhesive nanoparticles prepared from N-trimethyl chitosan (TMC) has been shown to increase their immunogenicity. However, because of their large size compared to soluble antigens, particles poorly diffuse through the nasal epithelium. The aim of this work was to study whether nasal vaccination with a much smaller TMC-antigen nanoconjugate would result in higher antibody responses as compared to TMC nanoparticles. TMC was covalently linked to a model antigen, ovalbumin (OVA), using thiol chemistry. For comparison, TMC/OVA nanoparticles and solutions of OVA and a physical mixture of TMC and OVA were made. As shown previously for TMC/OVA nanoparticles, TMC-OVA conjugate prolonged the nasal residence time of the antigen. TMC-OVA conjugate diffused significantly better through a monolayer of lung carcinoma (Calu-3) cells than TMC/OVA nanoparticles did. Moreover, nasal immunization of mice with the conjugate resulted in significantly more OVA positive DCs in the cervical lymph nodes as compared to TMC/OVA nanoparticles. Mice nasally immunized with TMC-OVA conjugate produced high levels of secretory IgA in nasal washes and higher titers of OVA-specific IgG than mice immunized with TMC/OVA nanoparticles after a priming dose. Moreover, as compared to TMC/OVA nanoparticles, TMC-OVA conjugate induced a more balanced IgG1/IgG2a response. In conclusion, the TMC-antigen nanoconjugate improves nasal delivery and immunogenicity of the antigen. This suggests that efficient codelivery of antigen and adjuvant to DCs, rather than a particulate form of the antigen/adjuvant combination, is decisive for the immunogenicity of the antigen.

Authors+Show Affiliations

Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21043518

Citation

Slütter, Bram, et al. "Antigen-adjuvant Nanoconjugates for Nasal Vaccination: an Improvement Over the Use of Nanoparticles?" Molecular Pharmaceutics, vol. 7, no. 6, 2010, pp. 2207-15.
Slütter B, Bal SM, Que I, et al. Antigen-adjuvant nanoconjugates for nasal vaccination: an improvement over the use of nanoparticles? Mol Pharm. 2010;7(6):2207-15.
Slütter, B., Bal, S. M., Que, I., Kaijzel, E., Löwik, C., Bouwstra, J., & Jiskoot, W. (2010). Antigen-adjuvant nanoconjugates for nasal vaccination: an improvement over the use of nanoparticles? Molecular Pharmaceutics, 7(6), 2207-15. https://doi.org/10.1021/mp100210g
Slütter B, et al. Antigen-adjuvant Nanoconjugates for Nasal Vaccination: an Improvement Over the Use of Nanoparticles. Mol Pharm. 2010 Dec 6;7(6):2207-15. PubMed PMID: 21043518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antigen-adjuvant nanoconjugates for nasal vaccination: an improvement over the use of nanoparticles? AU - Slütter,Bram, AU - Bal,Suzanne M, AU - Que,Ivo, AU - Kaijzel,Eric, AU - Löwik,Clemens, AU - Bouwstra,Joke, AU - Jiskoot,Wim, Y1 - 2010/11/02/ PY - 2010/11/4/entrez PY - 2010/11/4/pubmed PY - 2011/3/26/medline SP - 2207 EP - 15 JF - Molecular pharmaceutics JO - Mol. Pharm. VL - 7 IS - 6 N2 - Entrapment of antigens in mucoadhesive nanoparticles prepared from N-trimethyl chitosan (TMC) has been shown to increase their immunogenicity. However, because of their large size compared to soluble antigens, particles poorly diffuse through the nasal epithelium. The aim of this work was to study whether nasal vaccination with a much smaller TMC-antigen nanoconjugate would result in higher antibody responses as compared to TMC nanoparticles. TMC was covalently linked to a model antigen, ovalbumin (OVA), using thiol chemistry. For comparison, TMC/OVA nanoparticles and solutions of OVA and a physical mixture of TMC and OVA were made. As shown previously for TMC/OVA nanoparticles, TMC-OVA conjugate prolonged the nasal residence time of the antigen. TMC-OVA conjugate diffused significantly better through a monolayer of lung carcinoma (Calu-3) cells than TMC/OVA nanoparticles did. Moreover, nasal immunization of mice with the conjugate resulted in significantly more OVA positive DCs in the cervical lymph nodes as compared to TMC/OVA nanoparticles. Mice nasally immunized with TMC-OVA conjugate produced high levels of secretory IgA in nasal washes and higher titers of OVA-specific IgG than mice immunized with TMC/OVA nanoparticles after a priming dose. Moreover, as compared to TMC/OVA nanoparticles, TMC-OVA conjugate induced a more balanced IgG1/IgG2a response. In conclusion, the TMC-antigen nanoconjugate improves nasal delivery and immunogenicity of the antigen. This suggests that efficient codelivery of antigen and adjuvant to DCs, rather than a particulate form of the antigen/adjuvant combination, is decisive for the immunogenicity of the antigen. SN - 1543-8392 UR - https://www.unboundmedicine.com/medline/citation/21043518/Antigen_adjuvant_nanoconjugates_for_nasal_vaccination:_an_improvement_over_the_use_of_nanoparticles L2 - https://dx.doi.org/10.1021/mp100210g DB - PRIME DP - Unbound Medicine ER -