Inactivated vaccine with glycyrrhizic acid adjuvant elicits potent innate and adaptive immune responses against foot-and-mouth disease

Seokwon Shin; Hyeong Won Kim; Mi-Kyeong Ko; So Hui Park; Su-Mi Kim; Jong-Hyeon Park; Min Ja Lee

doi:10.3389/fmicb.2023.1289065

Inactivated vaccine with glycyrrhizic acid adjuvant elicits potent innate and adaptive immune responses against foot-and-mouth disease

Front Microbiol. 2023 Oct 31:14:1289065. doi: 10.3389/fmicb.2023.1289065. eCollection 2023.

Authors

Seokwon Shin^#¹, Hyeong Won Kim^#¹, Mi-Kyeong Ko¹, So Hui Park¹, Su-Mi Kim¹, Jong-Hyeon Park¹, Min Ja Lee¹

Affiliation

¹ Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do, Republic of Korea.

^# Contributed equally.

Abstract

Background: Foot-and-mouth disease (FMD) is an extremely contagious viral disease that is fatal to young animals and is a major threat to the agricultural economy by reducing production and limiting the movement of livestock. The currently commercially-available FMD vaccine is prepared using an inactivated viral antigen in an oil emulsion, with aluminum hydroxide [Al(OH)₃] as an adjuvant. However, oil emulsion-based options possess limitations including slow increases in antibody titers (up to levels adequate for defense against viral infection) and risks of local reactions at the vaccination site. Further, Al(OH)₃ only induces a T helper 2 (Th2) cell response. Therefore, novel adjuvants that can address these limitations are urgently needed. Glycyrrhizic acid (extracted from licorice roots) is a triterpenoid saponin and has great advantages in terms of price and availability.

Methods: To address the limitations of the currently used commercial FMD vaccine, we added glycyrrhizic acid as an adjuvant (immunostimulant) to the FMD bivalent (O PA2 + A YC) vaccine. We then evaluated its efficacy in promoting both innate and adaptive (cellular and humoral) immune reactions in vitro [using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs)] and in vivo (using mice and pigs).

Results: Glycyrrhizic acid has been revealed to induce an innate immune response and enhance early, mid-, and long-term immunity. The studied bivalent vaccine with glycyrrhizic acid increased the expression of immunoregulatory genes such as pattern-recognition receptors (PRRs), cytokines, transcription factors, and co-stimulatory molecules.

Conclusion: Collectively, glycyrrhizic acid could have utility as a novel vaccine adjuvant that can address the limitations of commercialized FMD vaccines by inducing potent innate and adaptive immune responses.

Keywords: adjuvant; foot-and-mouth disease; glycyrrhizic acid; immune response; innate and adaptive; vaccine.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Animal and Plant Quarantine Agency (APQA) (B-1543386-2021-24).