A Liposome-Based Adjuvant Containing Two Delivery Systems with the Ability to Induce Mucosal Immunoglobulin A Following a Parenteral Immunization

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 - 2019/2/26

Y1 - 2019/2/26

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

SN - 1936-0851

VL - 13

SP - 1116

EP - 1126

JO - ACS Nano

JF - ACS Nano

IS - 2

ER -