Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21

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.

Enhanced Immunogenicity and Protective Efficacy of a Campylobacter jejuni Conjugate Vaccine Coadministered with Liposomes Containing Monophosphoryl Lipid A and QS-21

“…These adjuvants often incorporate components that stimulate innate immune system receptors like Toll-like receptors (TLRs) and the inflammasome. The Walter Reed Army Institute of Research Laboratory of Adjuvant and Antigen Research has developed an Army Liposome Formulation (ALF) family of adjuvants that increase immunogenicity of a number of different vaccine platforms against a variety of pathogens, including HIV, Plasmodium falciparum, and Neisseria meningitidis (20)(21)(22)(23)(24). ALF is a liposome-based formulation containing a potent activator of TLR4, a synthetic form of monophospholipid A (MPLA) known as 3D-PHAD (Avanti Polar Lipids).…”

Novel Adjuvant Based on the Pore-Forming Protein Sticholysin II Encapsulated into Liposomes Effectively Enhances the Antigen-Specific CTL-Mediated Immune Response

“…Previous results obtained by our group demonstrated that DPPC: Cho (1:1) Lp encapsulating human epidermal growth factor are able to modulate the anti–human epidermal growth factor Ab response in mice to a mixed Th1/Th2 response, but they favored a Th1 pattern (50). The ability of Lp/OVA/StII to induce a Th1/Th2 mixed pattern could be desirable for a candidate vaccine that is addressed not only to intracellular targets (51). …”

Differential effect of HLA class-I versus class-II transgenes on human T and B cell reconstitution and function in NRG mice

“…The synthetic GIL (GILGFVFTL) peptide corresponds to the influenza A virus matrix protein, Mp58–66 and was obtained from Mimotopes Inc. The GIL peptide was encapsulated in liposomes containing neutral and anionic saturated phospholipids, cholesterol, and monophosphoryl lipid A (MPLA) as described 33 . The liposomes were obtained from the Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research.…”