The production, characterisation and application of monoclonal antibodies generated by immunisation with HIV-1C clade RGP140 envelope protein

Hassall, Mark; Page, Mark; Robinson, Mark; Jeffs, Simon A.; Jones, Ian M.; Chen, Hongying; Seaman, Michael S.; Ferguson, Debbie; Almond, Neil

doi:10.1016/j.jviromet.2013.08.011

Cited by 1 publication

(2 citation statements)

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“…The ALF SUV with an MPLA:phospholipid ratio of 1:5.6 and ALFQ MLV with a ratio of 1:220 appeared to induce the strongest and most consistent NAbs. As previously reported [24,26,27,42], the NAbs that we observed had limited reactivities with other viruses. Neutralization was not observed either with a tier 2 clade C pseudovirus or with a tier 1 clade B pseudovirus (data not shown).…”

Section: Discussionsupporting

confidence: 75%

“…The goal of this study was to explore the relative effects of seven different compositions of ALF-type formulations on the induction of immunity to CN54 gp140 antigen. The CN54 gp140 protein is useful as a model antigen in that it is a commercially available HIV-1 clade C trimeric envelope protein that has been used in human vaccine trials [23], and has been studied as a model antigen with various adjuvants [24][25][26][27][28]. Here we focused on the effects of different compositions of large multilamellar vesicle (MLV) liposomes and small unilamellar vesicle (SUV) liposomes, with or without QS21, on the induction of binding antibodies, IgG subtypes, IL-4 and IFN-γ production, and the induction of neutralizing antibodies to HIV-1 clade C.…”

Section: Introductionmentioning

confidence: 99%

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

Beck

Matyas

Jalah

et al. 2015

Vaccine

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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.

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Section: Discussionsupporting

confidence: 75%