Chemokine CCL20 plasmid improves protective efficacy of the Montanide ISA™ 206 adjuvanted foot-and-mouth disease vaccine in mice model

Chaudhari Jayeshbhai; Irshad Ahmed Hajam; Ashutosh Kumar Verma; Veerakyathappa Bhanuprakash; Ganesh Kondabattula; Subodh Kishore

doi:10.1016/j.vaccine.2018.07.003

Chemokine CCL20 plasmid improves protective efficacy of the Montanide ISA™ 206 adjuvanted foot-and-mouth disease vaccine in mice model

Vaccine. 2018 Aug 23;36(35):5318-5324. doi: 10.1016/j.vaccine.2018.07.003. Epub 2018 Jul 24.

Authors

Chaudhari Jayeshbhai¹, Irshad Ahmed Hajam², Ashutosh Kumar Verma¹, Veerakyathappa Bhanuprakash¹, Ganesh Kondabattula³, Subodh Kishore⁴

Affiliations

¹ Immunology Lab, FMD QCQA Unit, Indian Veterinary Research Institute, Bangalore 560024, India.
² Immunology Lab, FMD QCQA Unit, Indian Veterinary Research Institute, Bangalore 560024, India; College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea.
³ Immunology Lab, FMD QCQA Unit, Indian Veterinary Research Institute, Bangalore 560024, India. Electronic address: ganesh.kondabattula@icar.gov.in.
⁴ Immunology Lab, FMD QCQA Unit, Indian Veterinary Research Institute, Bangalore 560024, India. Electronic address: subodhkishore@ivri.res.in.

PMID: 30054161
DOI: 10.1016/j.vaccine.2018.07.003

Abstract

This study aimed to investigate the chemokine CCL20, a macrophage inflammatory protein-3 alpha, for adjuvant potential in inactivated foot-and-mouth disease (FMD) vaccine. Groups of mice were injected intramuscularly with either murine CCL20 DNA or CCL20 protein two days ahead of the immunization with Montanide ISA206 adjuvanted inactivated FMD vaccine and humoral and cellular immune responses were measured in post-vaccinal sera. We demonstrated that the mice immunized with CCL20 plasmid plus FMD vaccine showed earlier and significantly (p < 0.05) higher neutralizing antibody responses compared to the mice vaccinated with CCL20 protein plus FMD vaccine. In fact, CCL20 as a protein did not show any adjuvant effect and the immune responses induced in this group were comparable to that of the mice vaccinated with FMD vaccine alone. All the vaccination groups showed serum IgG1 and IgG2 antibody responses; however, the mice vaccinated with CCL20 plasmid plus FMD vaccine showed significantly (p < 0.05) higher IgG1 and IgG2 responses and the responses remained high at all-time points post vaccination, although not always statistically significant. Upon restimulation of the vaccinated splenocytes with the inactivated FMD viral antigen, significantly (p < 0.05) higher IFN-γ and IL-2 levels in culture supernatants were found in animals vaccinated with the CCL20 plasmid plus FMD vaccine, which is indicative of the T_H1 type of cellular immunity. On challenge with the homologous FMD virus on 28th day post immunization, CCL20 plasmid plus FMD vaccine showed complete protection (100%) while animals immunized with CCL20 protein plus FMD vaccine or FMD vaccine alone showed 66% protection. In summary, we show that prior injection of CCL20 plasmid improved protective efficacy of the inactivated FMD vaccine and thus offers a valuable strategy to modulate the efficacy and polarization of specific immunity against inactivated vaccines.

Keywords: Adjuvant; CCL20; Foot-and-mouth disease; Immune protection; Th1 immunity.

MeSH terms

Animals
Antibodies, Neutralizing / immunology
Chemokine CCL20 / genetics
Chemokine CCL20 / metabolism*
Female
Foot-and-Mouth Disease / immunology
Foot-and-Mouth Disease / prevention & control*
Foot-and-Mouth Disease Virus / immunology*
Foot-and-Mouth Disease Virus / pathogenicity*
Mice
Plasmids / genetics*
Vaccines, Inactivated / therapeutic use

Substances

Antibodies, Neutralizing
Chemokine CCL20
Vaccines, Inactivated