Conjugation of chitosan oligosaccharides via a carrier protein markedly improves immunogenicity of porcine circovirus vaccine
- 77 Downloads
Porcine circovirus type 2 (PCV2)-associated diseases have led to huge economic losses in pig industry. Our laboratory previously found that conjugation of chitosan oligosaccharides (COS) enhanced the immunogenicity of PCV2 vaccine against infectious pathogens. In this study, an effective adjuvant system was developed by covalent conjugation of COS via a carrier protein (Ovalbumin, OVA) to further increase the immunogenicity of vaccine. Its effect on dendritic cells maturation was assessed in vitro and its immunogenicity was investigated in mice. The results indicated that, as compared to the PCV2 and COS-PCV2, COS-OVA-PCV2 stimulated dendritic cells to express higher maturation markers (CD80, CD86, CD40 and MHC class II) and remarkably promoted both humoral and cellular immunity against PCV2 by enhancing the lymphocyte proliferation and inducing a mixed Th1/Th2 response, including the increased production of PCV2-specific antibodies and raised levels of inflammatory cytokines. Furthermore, it displayed better immune-stimulating effects than the physical mixture of vaccine and ISA206 (a commercialized adjuvant). In conclusion, conjugation of COS via a carrier protein might be a promising strategy to enhance the immunogenicity of vaccines.
KeywordsPorcine circovirus type 2 (PCV2) Chitosan oligosaccharide Conjugation Adjuvant system Carrier protein
We are grateful for the support by the National Key Research and Development Program of China (2017YFD0502303), and by National Natural Science Fund, China (NO. 31500747, NO. 31570801 and NO. U160820020).
Yuguang Du and Tao Hu designed the study. Guiqiang Zhang and Peiyuan Jia were responsible for the acquisition of data. Hongtao Liu and Guiqiang Zhang interpreted the experimental data. Guiqiang Zhang and Hongtao Liu were the major contributors in drafting and revising the manuscript. Hongtao Liu was final approval of the version to be submitted. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
This article contains animal studies, and all animal experiment procedures were approved by the Animal Ethical Experimentation Committee of Institute of Process Engineering, Chinese Academy of Sciences (Beijing, China).
- 4.Zhang, G., Cheng, G., Jia, P., Jiao, S., Feng, C., Hu, T., Liu, H., Du, Y.: The positive correlation of the enhanced immune response to PCV2 subunit vaccine by conjugation of chitosan oligosaccharide with the deacetylation degree. Marine Drugs. 15(8), 236 (2017)CrossRefPubMedCentralPubMedGoogle Scholar
- 7.Mellman, I., Coukos, G., Dranoff, G.: Cancer immunotherapy comes of age. Nat. Clin. Pract. Oncol. 2(3), 115 (2011)Google Scholar
- 11.Micoli, F., Romano, M.R., Tontini, M., Cappelletti, E., Gavini, M., Proietti, D., Rondini, S., Swennen, E., Santini, L., Filippini, S.: Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X. Proc. Natl. Acad. Sci. U. S. A. 110(47), 19077 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Tontini, M., Berti, F., Romano, M.R., Proietti, D., Zambonelli, C., Bottomley, M.J., De, G.E., Del, G.G., Rappuoli, R., Costantino, P.: Comparison of CRM197, diphtheria toxoid and tetanus toxoid as protein carriers for meningococcal glycoconjugate vaccines. Vaccine. 31(42), 4827–4833 (2013)CrossRefPubMedGoogle Scholar
- 17.Mwirigi, M., Nkando, I., Olum, M., Attahpoku, S., Ochanda, H., Berberov, E., Potter, A., Gerdts, V., Perezcasal, J., Wesonga, H.: Capsular polysaccharide from mycoplasma mycoides subsp. mycoides shows potential for protection against contagious bovine pleuropneumonia. Vet. Immunol. Immunopathol. 178, 64 (2016)CrossRefPubMedGoogle Scholar
- 22.Hu, T., Li, D., Wang, J., Wang, Q., Liang, Y., Su, Y., Ma, G., Su, Z., Wang, S.: Propylbenzmethylation at Val-1(α) markedly increases the tetramer stability of the PEGylated hemoglobin: a comparison with propylation at Val-1(α). Biochim. Biophys. Acta. 1820(12), 2044 (2012)CrossRefPubMedGoogle Scholar
- 23.Donadei, A., Balocchi, C., Mancini, F., Proietti, D., Gallorini, S., O'Hagan, D.T., D'Oro, U., Berti, F., Baudner, B.C., Adamo, R.: The adjuvant effect of TLR7 agonist conjugated to a meningococcal serogroup C glycoconjugate vaccine. Eur. J. Pharm. Biopharm. 107, 110 (2016)CrossRefPubMedGoogle Scholar
- 25.Gómezlaguna, J., Salguero, F.J., Pallarés, F.J., Fernández, D.M.M., Barranco, I., Cerón, J.J., Martínezsubiela, S., Van, R.K., Carrasco, L.: Acute phase response in porcine reproductive and respiratory syndrome virus infection. Comp. Immunol. Microbiol. Infect. Dis. 33(6), e51 (2010)CrossRefGoogle Scholar
- 35.Jin, J.O., Zhang, W., Du, J.Y., Yu, Q.: Correction for Jin et al., BDCA1-positive dendritic cells (DCs) represent a unique human myeloid DC subset that induces innate and adaptive immune responses to Staphylococcus aureus infection. Infect. Immun. 83(2), 849 (2015)CrossRefPubMedCentralPubMedGoogle Scholar