Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21. Issue 42 (13th October 2015)

• Record Type: Journal Article
• Authors: Beck, Zoltan; Matyas, Gary R.; Jalah, Rashmi; Rao, Mangala; Polonis, Victoria R.; Alving, Carl R.
• Is Part Of: Vaccine. Volume 33:Issue 42(2015)
• Page Start: 5578
• Page End: 5587
• Publication Date: 2015-10-13
• Subjects: ALF army liposome formulation -- ALFQ army liposome formulation plus added QS21 -- Chol cholesterol -- DMPC dimyristoyl phosphatidylcholine, DMPG, dimyristoyl phosphatidylglycerol -- IFN-γ interferon-γ -- IL-4 interleukin-4 -- MPLA monophosphoryl lipid A -- MLV multilamellar liposomal vesicles -- NAb neutralizing antibody -- PL phospholipids -- SUV small unilamellar liposomal vesicles; Adjuvants -- Liposomes -- Monophosphoryl lipid A -- QS21 -- HIV CN54 gp140 envelope protein -- AS01B; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.09.001
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Structural changes were made in Army Liposome Formulations (ALF) containing MPLA. Small ALF liposomes induced higher antibody titers than large ALF liposomes. QS21 converted small ALF liposomes to large ALFQ particles. ALF induced mainly IL-4 secretion and ALFQ induced both IFN-γ and IL-4. ALF and ALFQ both induced neutralizing antibodies to CN54 gp140. Abstract: Liposomes have shown promise as constituents of adjuvant formulations in vaccines to parasitic and viral diseases. A particular type of liposomal construct, referred to as Army Liposome Formulation (ALF), containing neutral and anionic saturated phospholipids, cholesterol, and monophosphoryl lipid A (MPLA), has been used as an adjuvant for many years. Here we investigated the effects of physical and chemical changes of ALF liposomes on adjuvanted immune responses to CN54 gp140, a recombinant HIV-1 envelope protein. While holding the total amounts of liposomal MPLA and the gp140 antigen constant, different liposome sizes and liposomal MPLA:phospholipid molar ratios, and the effect of adding QS21 to the liposomes were compared for inducing immune responses to the gp140. For liposomes lacking QS21, higher titers of IgG binding antibodies to gp140 were induced by small unilamellar vesicle (SUV) rather than by large multilamellar vesicle (MLV) liposomes, and the highest titers were obtained with SUV having the MPLA:phospholipid ratio of 1:5.6. ALF plus QS21 (ALFQ) liposomes induced the same maximal binding antibody titers regardless of the MPLA:phospholipid ratio. ALF MLV liposomes induced mainly IgG1 and very low IgG2a antibodies, while ALF SUV liposomes induced IgG1 ≥ IgG2a > IgG2b antibodies. Liposomes containing QS21 induced IgG1 > IgG2a > IgG2b > IgG3 antibodies. ELISPOT analysis of splenocytes from immunized mice revealed that ALF liposomes induced low levels of IFN-γ, but ALFQ induced high levels. ALF and ALFQ liposomes each induced approximately equivalent high levels of IL-4. Based on antibody subtypes and cytokine secretion, we conclude that ALF liposomes predominantly stimulate Th2, while ALFQ strongly induces both Th1 and Th2 immunity. When CN54 gp140 was adjuvanted with either ALF or ALFQ liposomes, antibodies were induced that neutralized two HIV-1 tier 1 clade C strain pseudoviruses.