Immune response of C57BL/6J mice to herpes zoster subunit vaccines formulated with nanoemulsion-based and liposome-based adjuvants

Herpes zoster (HZ) is a recurrent nerve tissue infection caused by the reactivation of varicella-zoster virus (VZV). At present, two vaccines, the live attenuated vaccine Zostavax™ and AS01B-adjuvanted recombinant subunit vaccine Shingrix™, are commercially available for HZ. The latter is superior to the former in terms of efficacy and duration of immunity in the elderly. In this study, we used glycoprotein E (gE) as an antigen, and investigated the effects of various adjuvants (MF59, MF59/CpG 2006, and MF59/QS-21) on the immune response of C57BL/6J mice to find an alternative adjuvant to AS01B-like adjuvant of liposome/QS-21/MPL. In addition to safety, the gE-specific antibody, IgG antibody subtype, and cytokine secretion by splenocytes, and cell-mediated immune responses were determined using ELISA and ELISPOT assays, respectively. Our results showed no significant effects on the body weight, temperature, or behavior of mice vaccinated with PBS or all adjuvanted vaccines. All adjuvanted vaccine groups showed significantly higher gE-specific IgG antibody levels than the gE-alone group on day 28 after the first vaccine dose. In addition, all adjuvants induced a remarkable increase in both IgG1 and IgG2b levels. However, MF59/QS-21 and MF59/CpG 2006 showed comparable capacities to those of liposome/QS-21/MPL in increasing the IgG2c levels, being superior to MF59. Further investigation revealed that MF59 only induced a limited increase in the levels of Th1 and Th2 cytokines, while MF59/QS-21, MF59/CpG 2006, and liposome/QS-21/MPL led to a significant increase in the secretion of interferon gamma (IFN-γ), IL-2, IL-4, and IL-10 and showed a Th1-biased immune response. Moreover, MF59/QS-21, MF59/CpG 2006, and liposome/QS-21/MPL adjuvanted vaccines resulted in comparable gE-specific IFN-γ + immune cell responses. These results suggest that the combination of MF59 with QS-21 or CpG 2006 may be a promising adjuvant candidate for subunit HZ vaccines. Further investigations are needed to illustrate their durability and efficacy in aged mice.