TY - JOUR
T1 - A Liposome-Based Adjuvant Containing Two Delivery Systems with the Ability to Induce Mucosal Immunoglobulin A Following a Parenteral Immunization
AU - Christensen, Dennis
AU - Bøllehuus Hansen, Lasse
AU - Leboux, Romain
AU - Jiskoot, Wim
AU - Christensen, Jan Pravsgaard
AU - Andersen, Peter
AU - Dietrich, Jes
PY - 2019
Y1 - 2019
N2 - Worldwide, enteric infections rank third among all causes of disease burdens, and vaccines able to induce a strong and long-lasting intestinal immune responses are needed. Parenteral immunization generally do not generate intestinal IgA. Recently, however, injections of retinoic acid (RA) dissolved in oil, administered multiple times before vaccination to precondition the vaccine-draining lymph nodes, enabled a parenteral vaccine strategy to induce intestinal IgA. As multiple injections of RA before vaccination is not an attractive strategy for clinical practice, we aimed to develop a "one injection" vaccine formulation that upon parenteral administration induced intestinal IgA. Our vaccine formulation contained two liposomal delivery systems. One delivery system, based on 1,2-distearoyl-sn-glycero-3-phosphocholine stabilized with PEG, was designed to exhibit fast drainage of RA to local lymph nodes to precondition these for a mucosal immune response before being subjected to the vaccine antigen. The other delivery system, based on the cationic liposomal adjuvant CAF01 stabilized with cholesterol, was optimized for prolonged delivery of the antigen by migratory antigen-presenting cells to the preconditioned lymph node. Combined we call the adjuvant CAF23. We show that CAF23, administered by the subcutaneous route induces an antigen specific intestinal IgA response, making it a promising candidate adjuvant for vaccines against enteric diseases.
AB - Worldwide, enteric infections rank third among all causes of disease burdens, and vaccines able to induce a strong and long-lasting intestinal immune responses are needed. Parenteral immunization generally do not generate intestinal IgA. Recently, however, injections of retinoic acid (RA) dissolved in oil, administered multiple times before vaccination to precondition the vaccine-draining lymph nodes, enabled a parenteral vaccine strategy to induce intestinal IgA. As multiple injections of RA before vaccination is not an attractive strategy for clinical practice, we aimed to develop a "one injection" vaccine formulation that upon parenteral administration induced intestinal IgA. Our vaccine formulation contained two liposomal delivery systems. One delivery system, based on 1,2-distearoyl-sn-glycero-3-phosphocholine stabilized with PEG, was designed to exhibit fast drainage of RA to local lymph nodes to precondition these for a mucosal immune response before being subjected to the vaccine antigen. The other delivery system, based on the cationic liposomal adjuvant CAF01 stabilized with cholesterol, was optimized for prolonged delivery of the antigen by migratory antigen-presenting cells to the preconditioned lymph node. Combined we call the adjuvant CAF23. We show that CAF23, administered by the subcutaneous route induces an antigen specific intestinal IgA response, making it a promising candidate adjuvant for vaccines against enteric diseases.
KW - adjuvant
KW - IgA
KW - intestine
KW - mucosa
KW - vaccine
U2 - 10.1021/acsnano.8b05209
DO - 10.1021/acsnano.8b05209
M3 - Journal article
C2 - 30609354
AN - SCOPUS:85060653396
VL - 13
SP - 1116
EP - 1126
JO - A C S Nano
JF - A C S Nano
SN - 1936-0851
IS - 2
ER -