Comparison of the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide on Japanese encephalitis vaccine in mice

Abstract

Adjuvants are essential vaccine components used to enhance, accelerate, and/or prolong adaptive immunity against specific vaccine antigens. In this study, we compared the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS), a toll-like receptor 4 agonist, on the Japanese encephalitis (JE) vaccine in mice. Mice were immunized once or twice at a two-week interval with inactivated JE vaccine in the absence or presence of adjuvant. We found that both the alum- and the liposome-based formulation induced significantly faster and higher serum IgG antibody responses as compared with the non-adjuvanted vaccine after either one or two immunizations. The antibody titers of the mouse immune sera correlated with 50% plaque reduction neutralization test (PRNT) antibody titers. In addition, the dLOS/liposome formulation was more effective in inducing a Th1-type immune response than the dLOS/alum formulation, as suggested by a strong antigen-specific interferon (IFN)-γ response. Based on these results, we suggest that both alum- and liposome-based adjuvant formulations containing dLOS may be used for the development of JE vaccines with improved immunogenicity.

The Effect of a TLR4 Agonist/Cationic Liposome Adjuvant on Varicella-Zoster Virus Glycoprotein E Vaccine Efficacy: Antigen Presentation, Uptake, and Delivery to Lymph Nodes

“…Unlike alum, liposomes are known to stimulate Th-1 type immunity when used as vaccine adjuvants. Both DOTAP-based and DDA-based cationic liposomes enhance the CMI response to vaccine antigens [42][43][44]. While liposomes alone stimulated the Th1-type response in the antigen-presentation assay, dLOS addition enhanced the effect (Figure 11).…”

“…We have previously developed a VZV gE subunit vaccine for the prevention of herpes zoster that elicited both humoral and cellular immune responses in a mouse model [44]. The vaccine contains an adjuvant formulation CIA09, composed of DOTAP-based cationic liposomes and the TLR4 agonist dLOS, which enhances antibody and cell-mediated immune responses to tuberculosis protein antigens and inactivated JEV vaccine [42,43]. In this study, we investigated the mechanism of action of CIA09 as an adjuvant for the model VZV gE antigen.…”

“…dLOS in combination with aluminum hydroxide (designated CIA06) has adjuvant activity in several viral and bacterial vaccines [38][39][40][41][42] and performed well in a phase I clinical study of a CIA06-adjuvanted human papillomavirus (HPV) virus-like particle (VLP) vaccine (unpublished data). We developed cationic liposome-based adjuvant CIA09, composed of DOTAP-based cationic liposomes and dLOS, which enhances antibody and cell-mediated immune responses to recombinant tuberculosis antigens, inactivated Japanese encephalitis vaccine (JEV), and recombinant varicella-zoster virus (VZV) glycoprotein E (gE) antigen [42][43][44]. CIA09 is particularly effective in eliciting a Th1-type biased response, as determined by interferon-γ (IFN-γ) cytokine production, compared with CIA06 [42][43][44].…”

“…It induces the secretion of cytokines from murine peritoneal macrophages similarly to MPL but with more potent activation of human monocytes and DCs [37]. dLOS in combination with aluminum hydroxide (designated CIA06) has adjuvant activity in several viral and bacterial vaccines [38][39][40][41][42] and performed well in a phase I clinical study of a CIA06-adjuvanted human papillomavirus (HPV) virus-like particle (VLP) vaccine (unpublished data). We developed cationic liposome-based adjuvant CIA09, composed of DOTAP-based cationic liposomes and dLOS, which enhances antibody and cell-mediated immune responses to recombinant tuberculosis antigens, inactivated Japanese encephalitis vaccine (JEV), and recombinant varicella-zoster virus (VZV) glycoprotein E (gE) antigen [42][43][44].…”

“…We developed cationic liposome-based adjuvant CIA09, composed of DOTAP-based cationic liposomes and dLOS, which enhances antibody and cell-mediated immune responses to recombinant tuberculosis antigens, inactivated Japanese encephalitis vaccine (JEV), and recombinant varicella-zoster virus (VZV) glycoprotein E (gE) antigen [42][43][44]. CIA09 is particularly effective in eliciting a Th1-type biased response, as determined by interferon-γ (IFN-γ) cytokine production, compared with CIA06 [42][43][44]. Using VZV gE as the model antigen, we investigated the mechanism of action of CIA09 and demonstrate here that liposomes and dLOS cooperatively promote (i) the immunogenicity of VZV gE antigen by increasing the antigen stability, (ii) antigen uptake at the site of injection (SOI), (iii) the recruitment of immune cells, (iv) antigen delivery to the lymph nodes, and v) antigen presentation by APCs to T cells.…”