Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins

Abstract

Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a novel vaccine capable of protecting subjects from chronic infection by HCV could greatly reduce the rates of HCV infection, subsequent liver pathogenesis, and in some cases death. Herein, we evaluated two different semi-synthetic archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral (levels of anti-E1/E2 IgG and HCV pseudoparticle neutralization) and cellular responses (numbers of antigen-specific cytokine-producing T cells) to those generated with adjuvant formulations composed of mimetics of commercial adjuvants including a squalene oil-in-water emulsion, aluminum hydroxide/monophosphoryl lipid A (MPLA) and liposome/MPLA/QS-21. In addition, we measured the longevity of these responses, tracking humoral, and cellular responses up to 6 months following vaccination. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, a simple admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells producing multiple cytokines such as IFN-γ, TNF-α, and IL-2. While liposome/MPLA/QS-21 as adjuvant generated superior cellular responses, the SLA E1/E2 admixed formulation was superior or equivalent to the other tested formulations in all immune parameters tested.

Adjuvanted Schistosoma mansoni-Cathepsin B With Sulfated Lactosyl Archaeol Archaeosomes or AddaVax™ Provides Protection in a Pre-Clinical Schistosomiasis Model

“…As previously mentioned, both SLA and AddaVax have been shown to activate the immune system (23)(24)(25)27) and it is due to this quality that they have been exploited as vaccine adjuvants. This study sought to assess the increased efficacy of SmCB when combined with these compounds, however further studies should be conducted to elucidate the possible protective effects of the adjuvants themselves in schistosomiasis infection.…”

“…In this work we evaluated the protective capabilities of two new adjuvants: sulfated lactosyl archaeol (SLA) archaeosomes and AddaVax, a squalene-based oil-in-water emulsion similar to MF59. When used as an adjuvant, SLA has been shown to activate strong humoral and cell-mediated responses against multiple antigens by increasing local cytokine production, immune cell trafficking, and antigen uptake at the injection site, leading to increased protection in murine models of infectious disease and cancer (23)(24)(25). In this study, we used a novel admixed formulation which provides a simple ready to mix adjuvant formulation with no loss of antigen during the formulation process (26).…”

Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants

“…However, many vaccine preclinical studies centered on E1, E2, or E1E2 proteins combined with different adjuvants are ongoing ( Table 4 ). In this regard, rE1E2 immunogenicity has been tested in combination with varying adjuvants in mice [ 179 , 180 ]. The cyclic di-adenosine monophosphate (c-di-AMP) (a STING activator) or liposomes (archaeosomes) composed of sulfated lactosyl archaeol (SLA, a semi-synthetic archaeal lipid) induced a more potent Th1 type CD4 + T-cell response compared with M59 or alum/MPLA adjuvants [ 179 ].…”

“…At the same time, archaeosomes activate APCs and cytokine production [ 181 , 182 ], leading to a potent adjuvant activity [ 183 ]. Similar to MF59 and AS01 mimetics, SLA archaeosomes also induce long-lasting immunity in mice [ 180 ]. In addition to archaeosomes and c-di-AMP, enhanced CD4 + T-cells levels were observed in mice immunized with rE1E2 adjuvanted with an AS01 mimetic [ 180 ].…”

“…Similar to MF59 and AS01 mimetics, SLA archaeosomes also induce long-lasting immunity in mice [ 180 ]. In addition to archaeosomes and c-di-AMP, enhanced CD4 + T-cells levels were observed in mice immunized with rE1E2 adjuvanted with an AS01 mimetic [ 180 ]. Further investigations on new combinations of SLA with other adjuvants, such as TLR agonists, will give us a more detailed picture of the adjuvant landscape.…”