Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy.
This study describes the feasibility and adjuvant mechanism of a degradable emulsion for tuning adaptive immune responses to a vaccine antigen. We featured a mouse model with ovalbumin (OVA) as the antigen to deepen our understanding of the properties of a degradable emulsion-based adjuvant, dubbed PELC, interacting with immune cells and to elucidate their roles in vaccine immunogenicity in vivo. First, we demonstrated that the emulsion, which is stabilized by an amphiphilic bioresorbable polymer, shows degradation in mimic human body conditions and considerable tolerance in vivo. Then, we confirmed the model protein could be loaded into the emulsion and released from the matrix in a sustained manner, subsequently driving the production of antigen-specific antibodies. We also comprehended that PELC not only recruits antigen-presenting cells (APCs) to the injection site but also induces the activation of the recruited APCs and migration to the draining lymph nodes. As an adjuvant for cancer immunotherapy, PELC-formulated OVA could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated OVA, using OVA protein/EG7 cells as a tumor antigen/tumor cell model. Accordingly, our data paved the way for the clinical application of degradable emulsions based on amphiphilic bioresorbable polymers as vaccine adjuvants.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
Chung-Hsiung
CH
Huang
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
Chiung-Yi
CY
Huang
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
Chih-Ping
CP
Cheng
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
Shih-Hsiung
SH
Dai
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
Hsin-Wei
HW
Chen
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
Chih-Hsiang
CH
Leng
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
Pele
P
Chong
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
Shih-Jen
SJ
Liu
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
Ming-Hsi
MH
Huang
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D002460:Cell Line; D004655:Emulsions; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000951:Antigens, Neoplasm; D004655:Emulsions; D011091:Polyesters; D014612:Vaccines; C000613452:poly(ethylene glycol)-b-poly(lactide-co-epsilon-caprolactone); D011092:Polyethylene Glycols