Adsorption of protein antigen to the cationic liposome adjuvant CAF®01 is required for induction of Th1 and Th17 responses but not for antibody induction
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Adsorption of protein antigen to the cationic liposome adjuvant CAF®01 is required for induction of Th1 and Th17 responses but not for antibody induction. / Wørzner, Katharina; Hvannastein, Jóhanna; Tandrup Schmidt, Signe; Foged, Camilla; Rosenkrands, Ida; Kristian Pedersen, Gabriel; Christensen, Dennis.
In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Vol. 165, 2021, p. 293-305.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Adsorption of protein antigen to the cationic liposome adjuvant CAF®01 is required for induction of Th1 and Th17 responses but not for antibody induction
AU - Wørzner, Katharina
AU - Hvannastein, Jóhanna
AU - Tandrup Schmidt, Signe
AU - Foged, Camilla
AU - Rosenkrands, Ida
AU - Kristian Pedersen, Gabriel
AU - Christensen, Dennis
N1 - Copyright © 2021. Published by Elsevier B.V.
PY - 2021
Y1 - 2021
N2 - The degree of antigen adsorption to adjuvants in subunit vaccines may significantly influence the immune responses they induce upon vaccination. Commonly used approaches for studying how the level of adsorption affects the induction of antigen-specific immune responses include (i) using adjuvants with different abilities to adsorb antigens, and (ii) comparing different antigens selected based on their ability to adsorb to the adjuvant. A weakness of these approaches is that only the antigen adsorption level is varied, but also other important functional factors such as adjuvant composition and/or the B/T cell epitopes, which may affect immunogenicity. Hence, we investigated how changing the adsorption capabilities of a single antigen to an adjuvant influenced the vaccine-induced immune responses. The model antigen lysozyme, which displays a positive net charge at physiological pH due to an isoelectric point (pI) of 11, was succinylated to different extents, resulting in a reduction of the pI value to 4.4 - 5.9, depending on the degree of succinylation. A pronounced inverse correlation was found between the pI value of the succinylated lysozyme analogues and the degree of adsorption to a cationic liposomal adjuvant consisting of dimethyldioctadecylammonium bromide (DDA) and trehalose dibehenate (TDB) (CAF®01). Furthermore, increased adsorption to this adjuvant correlated directly with the magnitude of lysozyme-specific Th1/Th17 immune responses induced by the vaccine in mice, while there was an inverse correlation with antibody induction. However, high lysozyme-specific antibody titers were induced with an increased antigen dose, even upon vaccination with a strongly adsorbed succinylated lysozyme analogue. Hence, these data illustrate that the degree of lysozyme adsorption to CAF®01 strongly affects the quality of the resulting immune responses.
AB - The degree of antigen adsorption to adjuvants in subunit vaccines may significantly influence the immune responses they induce upon vaccination. Commonly used approaches for studying how the level of adsorption affects the induction of antigen-specific immune responses include (i) using adjuvants with different abilities to adsorb antigens, and (ii) comparing different antigens selected based on their ability to adsorb to the adjuvant. A weakness of these approaches is that only the antigen adsorption level is varied, but also other important functional factors such as adjuvant composition and/or the B/T cell epitopes, which may affect immunogenicity. Hence, we investigated how changing the adsorption capabilities of a single antigen to an adjuvant influenced the vaccine-induced immune responses. The model antigen lysozyme, which displays a positive net charge at physiological pH due to an isoelectric point (pI) of 11, was succinylated to different extents, resulting in a reduction of the pI value to 4.4 - 5.9, depending on the degree of succinylation. A pronounced inverse correlation was found between the pI value of the succinylated lysozyme analogues and the degree of adsorption to a cationic liposomal adjuvant consisting of dimethyldioctadecylammonium bromide (DDA) and trehalose dibehenate (TDB) (CAF®01). Furthermore, increased adsorption to this adjuvant correlated directly with the magnitude of lysozyme-specific Th1/Th17 immune responses induced by the vaccine in mice, while there was an inverse correlation with antibody induction. However, high lysozyme-specific antibody titers were induced with an increased antigen dose, even upon vaccination with a strongly adsorbed succinylated lysozyme analogue. Hence, these data illustrate that the degree of lysozyme adsorption to CAF®01 strongly affects the quality of the resulting immune responses.
U2 - 10.1016/j.ejpb.2021.05.020
DO - 10.1016/j.ejpb.2021.05.020
M3 - Journal article
C2 - 34044110
VL - 165
SP - 293
EP - 305
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
ER -
ID: 269724310