title: Adjuvant formulations possess differing efficacy in the potentiation of antibody and cell mediated responses to a human malaria vaccine under selective immune genes knockout environment.
abstract: Infections and chronic diseases can alter the host's immunological balance or result in immunodeficiencies. We hypothesize that this may also affect the performance of vaccine adjuvants. Accordingly, the potency and adjuvanticity of eight adjuvant formulations based on Montanide ISA720, MF59, monophosphoryl lipid A (MPL), QS21 (saponin derivative), MPL-SE (stable emulsion of a MPL derivative), and MPL-AF (MPL in aqueous formulation) were studied in immune gene knockout mice, IFN-gamma -/-, IL-4 -/-, and STAT6 -/-, using the P. falciparum MSP1 vaccine, P30P2MSP1-19 as a model immunogen. The adjuvants showed preferential requirements for the immune mediators to induce immune responses to MSP1-19, and the effects were formulation-specific. While emulsion-type adjuvants were highly effective in mice, their potency was more readily suppressed by immune knockouts; and additions of immunomodulators were required to restore efficacy. Formulated adjuvants had characteristics distinct from their individual components, and multi-components formulations were not necessarily superior. We conclude that perturbation of immune environments will have measurable impact on adjuvants' potency. Evaluation of adjuvants in immune knockout models may be a supplementary approach to measure and compare adjuvants' efficacy, and to further unveil their distinct biological activities.
authors.affiliation: Department of Tropical Medicine and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, HI 96813, USA. ghui@hawaii.edu <ghui@hawaii.edu>
authors.forename: George S
authors.initials: GS
authors.lastname: Hui
authors.forename: Caryn N
authors.initials: CN
authors.lastname: Hashimoto
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007132:Immunoglobulin Isotypes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D007371:Interferon-gamma