TY - JOUR
T1 - Exosomes as adjuvants for the recombinant hepatitis B antigen
T2 - First report
AU - Jesus, Sandra
AU - Soares, Edna
AU - Cruz, Maria Teresa
AU - Borges, Olga
N1 - Funding Information:
This work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0145-FEDER-000008:BrainHealth 2020, and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Foundation for Science and Technology , I.P., under project POCI-01-0145-FEDER-007440 and POCI-01-0145-FEDER-030331. TEM microscopy analyses were performed at IBILI under FCT founding contract PPBI-POCI-01-0145-FEDER-022122. Sandra Jesus thanks FCT PhD fellowship DFRH - SFRH/BD/81350/2011 and post-doc ProSafe/0001/2016 project fellowship and thanks Mónica Zuzarte and Ana Donato for technical expertise in TEM microscopy and spleen cell counting respectively.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/12
Y1 - 2018/12
N2 - Over the past few years, exosomes, a class of extracellular vesicles (EVs), have emerged as key players for inter-cellular communication ultimately modulating the behavior of target cells with countless outcomes. Nevertheless, the potential role of exosomes as vaccine adjuvants remains largely unexplored. Herein, we hypothesized that exosomes derived from immune cells may have an immunostimulatory effect and could constitute a good target towards the development of new fine-tuned vaccine adjuvants. To accomplish this goal, exosomes isolated from lipopolysaccharide endotoxin (LPS)-stimulated human monocytic cell line (THP-1) were characterized and tested for their non-specific immunostimulatory activity when administered subcutaneously to healthy mice; additionally, exosomes’ vaccine adjuvant ability was also disclosed after their inclusion in vaccine formulations. The results obtained suggested that the isolated exosomes evoked a pro-inflammatory profile in spleen cells of healthy mice through the induction of cytokines such as tumor necrosis factor alpha (TNF-α), chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) and interleukin 1 beta (IL-1β). Moreover, subcutaneous vaccination of mice with exosomes combined with a solution of hepatitis B recombinant antigen (HBsAg) or combined with a suspension containing HBsAg loaded poly-ε-caprolactone (PCL)/chitosan nanoparticles (NPs), induced a humoral immune response quite similar to the one achieved with the experimental control group (HBsAg solution without exosomes). However, exosomes triggered an immunomodulator effect on the cellular immune response, highlighted by the enhancement of IFN-γ secretion. To the best of authors knowledge, this is the first report describing extensively the role of unmodified exosomes as adjuvants and co-adjuvants for hepatitis B vaccination strategies.
AB - Over the past few years, exosomes, a class of extracellular vesicles (EVs), have emerged as key players for inter-cellular communication ultimately modulating the behavior of target cells with countless outcomes. Nevertheless, the potential role of exosomes as vaccine adjuvants remains largely unexplored. Herein, we hypothesized that exosomes derived from immune cells may have an immunostimulatory effect and could constitute a good target towards the development of new fine-tuned vaccine adjuvants. To accomplish this goal, exosomes isolated from lipopolysaccharide endotoxin (LPS)-stimulated human monocytic cell line (THP-1) were characterized and tested for their non-specific immunostimulatory activity when administered subcutaneously to healthy mice; additionally, exosomes’ vaccine adjuvant ability was also disclosed after their inclusion in vaccine formulations. The results obtained suggested that the isolated exosomes evoked a pro-inflammatory profile in spleen cells of healthy mice through the induction of cytokines such as tumor necrosis factor alpha (TNF-α), chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) and interleukin 1 beta (IL-1β). Moreover, subcutaneous vaccination of mice with exosomes combined with a solution of hepatitis B recombinant antigen (HBsAg) or combined with a suspension containing HBsAg loaded poly-ε-caprolactone (PCL)/chitosan nanoparticles (NPs), induced a humoral immune response quite similar to the one achieved with the experimental control group (HBsAg solution without exosomes). However, exosomes triggered an immunomodulator effect on the cellular immune response, highlighted by the enhancement of IFN-γ secretion. To the best of authors knowledge, this is the first report describing extensively the role of unmodified exosomes as adjuvants and co-adjuvants for hepatitis B vaccination strategies.
KW - Exosomes
KW - Extracellular vesicles
KW - HBsAg
KW - Poly-ε-caprolactone/chitosan nanoparticles
KW - Vaccine adjuvant
UR - http://www.scopus.com/inward/record.url?scp=85054173231&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2018.09.029
DO - 10.1016/j.ejpb.2018.09.029
M3 - Article
C2 - 30287267
AN - SCOPUS:85054173231
SN - 0939-6411
VL - 133
SP - 1
EP - 11
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -