Fusion-expressed CTB improves both systemic and mucosal T-cell responses elicited by an intranasal DNA priming/intramuscular recombinant vaccinia boosting regimen.

Sugan Qiu,Xiaoyan Zhang,Yinyin Ben,Xiaonan Ren,Jing Wang,Yanmin Wan,Yanqin Ren,Jianqing Xu

doi:10.1155/2014/308732

Sugan Qiu, Xiaoyan Zhang + Show 6 more

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https://doi.org/10.1155/2014/308732

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Abstract

Previous study showed that CTB (Cholera toxin subunit B) can be used as a genetic adjuvant to enhance the systemic immune responses. To further investigate whether it can also be used as a genetic adjuvant to improve mucosal immune responses, we constructed DNA and recombinant Tiantan vaccinia (rTTV) vaccines expressing OVA-CTB fusion antigen. Female C57BL/6 mice were immunized with an intranasal DNA priming/intramuscular rTTV boosting regimen. OVA specific T-cell responses were measured by IFN-γ ELISPOT and specific antibody responses were determined by ELISA. Compared to the nonadjuvant group (pSV-OVA intranasal priming/rTTV-OVA intramuscular boosting), pSV-OVA-CTB intranasal priming/rTTV-OVA-CTB intramuscular boosting group significantly improved the magnitudes of T-cell responses at spleen (1562 ± 567 SFCs/106 splenocytes versus 330 ± 182 SFCs/106 splenocytes, P < 0.01), mesenteric LN (96 ± 83 SFCs/106 lymphocytes versus 1 ± 2 SFCs/106 lymphocytes, P < 0.05), draining LNs of respiratory tract (109 ± 60 SFCs/106 lymphocytes versus 2 ± 2 SFCs/106 lymphocytes, P < 0.01) and female genital tract (89 ± 48 SFCs/106 lymphocytes versus 23 ± 21 SFCs/106 lymphocytes, P < 0.01). These results collectively demonstrated that fusion-expressed CTB could act as a potent adjuvant to improve both systemic and mucosal T-cell responses.

Highlights

DNA vaccines are insufficient to stimulate strong mucosal and systemic immunity when inoculated alone [1]
Recent studies suggested that both CTA (Cholera toxin subunit A) and CTB (Cholera toxin subunit B) can be used as genetic adjuvants to boost the systemic immune responses elicited by DNA vaccines [5, 6]
To investigate whether CTB can be used as a genetic adjuvant to improve antigen specific mucosal immune responses, in this study, we constructed DNA and recombinant Tiantan vaccinia vaccines encoding OVA-CTB fusion antigen and tested their immunogenicity in an intranasal DNA priming/intramuscular rTTV boosting regimen, which has been proved to be able to raise vigorous mucosal and systemic immune response [7]

Summary

Introduction

DNA vaccines are insufficient to stimulate strong mucosal and systemic immunity when inoculated alone [1]. Various approaches have been taken to improve the immunogenicity of DNA vaccine, such as delivering DNA by using electroporation or enhancing host response by coadminstration of genetic adjuvants [1]. Recent studies suggested that both CTA (Cholera toxin subunit A) and CTB (Cholera toxin subunit B) can be used as genetic adjuvants to boost the systemic immune responses elicited by DNA vaccines [5, 6]. To investigate whether CTB can be used as a genetic adjuvant to improve antigen specific mucosal immune responses, in this study, we constructed DNA and recombinant Tiantan vaccinia (rTTV) vaccines encoding OVA-CTB fusion antigen and tested their immunogenicity in an intranasal DNA priming/intramuscular rTTV boosting regimen, which has been proved to be able to raise vigorous mucosal and systemic immune response [7]

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Discussion

Conclusion