Exosomes as adjuvants for the recombinant hepatitis B antigen: First report

• Published in: European journal of pharmaceutics and biopharmaceutics 2018-12, Vol.133, p.1-11
• Main Authors: Jesus, Sandra, Soares, Edna, Cruz, Maria Teresa, Borges, Olga
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - genetics; Animals; Cell Line; Chemokine CCL5 - genetics; Exosomes; Exosomes - genetics; Extracellular vesicles; Female; HBsAg; Hepatitis B Antigens - genetics; Hepatitis B Vaccines - genetics; Humans; Immunity, Cellular - genetics; Immunity, Humoral - genetics; Interleukin-1beta - genetics; Mice; Mice, Inbred C57BL; Poly-ε-caprolactone/chitosan nanoparticles; Recombinant Proteins - genetics; Tumor Necrosis Factor-alpha - genetics; Vaccination - methods; Vaccine adjuvant; Viral Vaccines - genetics
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2018.09.029

[Display omitted] 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.