Systematic investigation of the role of surfactant composition and choice of oil: Design of a nanoemulsion-based adjuvant inducing concomitant humoral and CD4+ T-cell responses
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Systematic investigation of the role of surfactant composition and choice of oil : Design of a nanoemulsion-based adjuvant inducing concomitant humoral and CD4+ T-cell responses. / Schmidt, Signe Tandrup; Neustrup, Malene Aaby; Harloff-Helleberg, Stine; Korsholm, Karen Smith; Rades, Thomas; Andersen, Peter; Christensen, Dennis; Foged, Camilla.
In: Pharmaceutical Research, Vol. 34, No. 8, 08.2017, p. 1716-1727.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Systematic investigation of the role of surfactant composition and choice of oil
T2 - Design of a nanoemulsion-based adjuvant inducing concomitant humoral and CD4+ T-cell responses
AU - Schmidt, Signe Tandrup
AU - Neustrup, Malene Aaby
AU - Harloff-Helleberg, Stine
AU - Korsholm, Karen Smith
AU - Rades, Thomas
AU - Andersen, Peter
AU - Christensen, Dennis
AU - Foged, Camilla
PY - 2017/8
Y1 - 2017/8
N2 - PURPOSE:Induction of cell-mediated immune (CMI) responses is crucial for vaccine-mediated protection against difficult vaccine targets, e.g., Chlamydia trachomatis (Ct). Adjuvants are included in subunit vaccines to potentiate immune responses, but many marketed adjuvants stimulate predominantly humoral immune responses. Therefore, there is an unmet medical need for new adjuvants, which potentiate humoral and CMI responses. The purpose was to design an oil-in-water nanoemulsion adjuvant containing a synthetic CMI-inducing mycobacterial monomycoloyl glycerol (MMG) analogue to concomitantly induce humoral and CMI responses.METHODS:The influence of emulsion composition was analyzed using a systematic approach. Three factors were varied: i) saturation of the oil phase, ii) type and saturation of the applied surfactant mixture, and iii) surfactant mixture net charge.RESULTS:The emulsions were colloidally stable with a droplet diameter of 150-250 nm, and the zeta-potential correlated closely with the net charge of the surfactant mixture. Only cationic emulsions containing the unsaturated surfactant mixture induced concomitant humoral and CMI responses upon immunization of mice with a Ct antigen, and the responses were enhanced when squalene was applied as the oil phase. In contrast, emulsions with neutral and net negative zeta-potentials did not induce CMI responses. The saturation degree of the oil phase did not influence the adjuvanticity.CONCLUSION:Cationic, MMG analogue-containing nanoemulsions are potential adjuvants for vaccines against pathogens for which both humoral and CMI responses are needed.
AB - PURPOSE:Induction of cell-mediated immune (CMI) responses is crucial for vaccine-mediated protection against difficult vaccine targets, e.g., Chlamydia trachomatis (Ct). Adjuvants are included in subunit vaccines to potentiate immune responses, but many marketed adjuvants stimulate predominantly humoral immune responses. Therefore, there is an unmet medical need for new adjuvants, which potentiate humoral and CMI responses. The purpose was to design an oil-in-water nanoemulsion adjuvant containing a synthetic CMI-inducing mycobacterial monomycoloyl glycerol (MMG) analogue to concomitantly induce humoral and CMI responses.METHODS:The influence of emulsion composition was analyzed using a systematic approach. Three factors were varied: i) saturation of the oil phase, ii) type and saturation of the applied surfactant mixture, and iii) surfactant mixture net charge.RESULTS:The emulsions were colloidally stable with a droplet diameter of 150-250 nm, and the zeta-potential correlated closely with the net charge of the surfactant mixture. Only cationic emulsions containing the unsaturated surfactant mixture induced concomitant humoral and CMI responses upon immunization of mice with a Ct antigen, and the responses were enhanced when squalene was applied as the oil phase. In contrast, emulsions with neutral and net negative zeta-potentials did not induce CMI responses. The saturation degree of the oil phase did not influence the adjuvanticity.CONCLUSION:Cationic, MMG analogue-containing nanoemulsions are potential adjuvants for vaccines against pathogens for which both humoral and CMI responses are needed.
U2 - 10.1007/s11095-017-2180-9
DO - 10.1007/s11095-017-2180-9
M3 - Journal article
C2 - 28516400
VL - 34
SP - 1716
EP - 1727
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
IS - 8
ER -
ID: 177413302