Alarmin IL-33 elicits potent TB-specific cell-mediated responses

Abstract

Tuberculosis (TB) still remains a major public health issue despite the current available vaccine for TB, Bacille Calmette Guerin (BCG). An effective vaccine against TB remains a top priority in the fight against this pandemic bacterial infection. Adequate protection against TB is associated with the development of T_H1-type and CD8⁺ T cell responses. One alarmin cytokine, interleukin 33 (IL-33), has now been implicated in the development of both CD4⁺ T_H1 and CD8⁺ T cell immunity. In this study, we determined whether the administration of IL-33 as an adjuvant, encoded in a DNA plasmid, could enhance the immunogenicity of a TB DNA vaccine. We report that the co-immunization of IL-33 with a DNA vaccine expressing the Mycobacterium Tuberculosis (Mtb) antigen 85B (Ag85B) induced robust Ag85B-specific IFNγ responses by ELISpot compared to Ag85B alone. Furthermore, these enhanced responses were characterized by higher frequencies of Ag85B-specific, multifunctional CD4⁺ and CD8⁺ T cells. Vaccination with IL-33 also increased the ability of the Ag85B-specific CD8⁺ T cells to undergo degranulation and to secrete IFNγ and TNFα cytokines. These finding highlights IL-33 as a promising adjuvant to significantly improve the immunogenicity of TB DNA vaccines and support further study of this effective vaccine strategy against TB.

Keywords:

• adjuvants
• DNA vaccines
• Interleukin 33
• tuberculosis
• TB vaccines

Funding

This research was supported by Inovio Pharmaceuticals and Aeras.

Disclosure of Potential Conflicts of Interest

D.B.W. has grant funding, participates in industry collaborations, receives speaking honoraria, and collects fees for consulting. He serves on scientific review committees and advisory boards. Remuneration includes direct payments, stock, or stock options. In the interest of disclosure, he therefore notes potential conflicts associated with this work with Pfizer, Bristol Myers Squibb, Inovio, Touchlight, oncosec, Merck, VGXI, and possibly others. Licensing of technology from his laboratory has created over 100 jobs in the private sector in the biotech/pharma industry. The other authors declare no competing financial interests.

Acknowledgments

We would like to acknowledge all members of the Weiner Laboratory for contributions and/or critical reading of this manuscript. The authors also thank Penn CFAR and ACC core facilities for their support.