A novel adjuvant system BK-02 with CpG2006 and MF59 enhances the immunogenicity of a herpes zoster subunit vaccine.

INTRODUCTION

Reactivation of the varicella-zoster virus (VZV) results in herpes zoster (HZ), which can lead to complications such as postherpetic neuralgia. The commercially available HZ subunit adjuvanted vaccine, Shingrix®, offers significant protection against HZ in older adults. However, the adjuvant system of this vaccine has limitations that necessitate the development of alternative adjuvant systems.

METHODS

In this study, we established a novel adjuvant system, BK-02, composed of both the Toll-like receptor 9 (TLR9) agonist BK-02C (CpG2006) and a squalene-based oil-in-water emulsion, BK-02M (MF59), using ELISA, ELISpot, and flow cytometry analyses.

RESULTS

Our results showed that when combined with glycoprotein E (gE), the active ingredient of a recombinant HZ vaccine, the BK-02 adjuvant system elicited significantly higher gE-specific IFN-γ+ T-cell responses (486 SFU/10⁶ cells, 121-fold increase vs gE alone) and IgG antibody titers (Lg titers 5.2 vs 3.4 for gE alone). The optimal dose (5 μg gE + 30 μg BK-02C + 1× BK-02M) for inducing gE protein-specific cellular immunity was determined in mice. This corresponded to a clinical dose of "50 μg gE + 300/500 μg BK-02C + 0.5 mL BK-02M." Additionally, pilot-scale samples of the recombinant HZ vaccine demonstrated enhanced gE-specific CD4+ and CD8+ T-cell immune responses, compared to Shingrix®. Moreover, the gE/BK-02 adjuvant system induced a Th1-regulated mixed immune response, enabling robust cellular and humoral immunity.

DISCUSSION: These findings indicated that the BK-02 adjuvant system is a promising adjuvant candidate for the current HZ subunit vaccines.