Search

Varicella zoster virus (VZV) is a neurotropic and lymphotropic alpha herpesvirus that causes varicella and herpes zoster (HZ). At a primary infection, VZV causes varicella in young children. Reactivation of latent VZV in sensory ganglia causes painful HZ in elderly people, occasionally leading to a serious complication, postherpetic neuralgia (PHN). A live attenuated VZV vaccine, the first vaccine licensed for the prevention of HZ and PHN is not very effective, while a recombinant subunit vaccine provides higher and longer protection against HZ. In the present study, we developed a new adjuvant system CIA09A, which is composed of cationic liposomes, the Toll-like receptor 4 (TLR4) agonist de-O-acylated lipooligosaccharide, and Quillaja saponin fraction QS-21. We then determined its adjuvant activity for recombinant VZV glycoprotein E (gE) in mice. Co-lyophilization of the liposomal adjuvant formulation with gE did not abolish the immune-stimulating activity. In fact, the CIA09A-adjuvanted gE vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE protein and VZV in a VZV-primed mouse model. Furthermore, the frequency of gE-specific polyfunctional CD4+ T cells expressing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2 was significantly increased in mice immunized with the adjuvanted vaccine. These data indicate that co-lyophilization of protein antigens with CIA09A enables development of a liposome-adjuvanted vaccine in a single vial to induce strong cell-mediated immunity required for vaccine efficacy. Thus, the CIA09A-adjuvanted gE vaccine warrants further development as a new prophylactic vaccine against HZ.

CIA05 is a toll-like receptor (TLR) 4 agonist derived from an Escherichia coli lipopolysaccharide (LPS) mutant and has been shown to have potential as a vaccine adjuvant. In this study, we investigated the immunopotentiating activity of the adjuvant system CIA06, which is comprised of CIA05 and aluminum hydroxide (alum), when used with the human papillomavirus (HPV) L1 virus-like particles (VLPs) vaccine. BALB/c mice were immunized intramuscularly three times at 2-week intervals with HPV16 L1 VLPs alone or in the presence of various combinations of CIA05 and alum, and the immune responses were assessed. We found that the combination of CIA05 and alum at a ratio of 1:50 (designated CIA06B) yielded the highest immune response in terms of serum anti-HPV L1 VLP IgG antibody titers, splenocyte interferon (IFN)-γ secretion, and antigen-specific memory B cell responses. The immunogenicity of the CIA06B-adjuvanted HPV16/18 L1 VLP vaccine was compared with that of the currently licensed HPV vaccine Cervarix™. The CIA06B-adjuvanted vaccine was similar to Cervarix™ with regard to eliciting serum antigen-specific IgG antibodies and virus-neutralizing antibodies but more effective at inducing splenic cytokine production and memory B cells. We also observed that the antigen-specific IgG antibody titers, splenic IFN-γ secretion and memory B cells induced by the CIA06B-adjuvanted HPV vaccine remained high up to 24 weeks post-immunization. Based on these data, we concluded that CIA06B may have potential as an adjuvant in a potent prophylactic vaccine against HPV infection.