Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier |
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Authors: | Jannatul Firdous Mohammad Ariful Islam Sung-Moo Park In-Su Cheon Byoung-Shik Shim Hyo-Shin Yoon Manki Song Jun Chang Yun-Jaie Choi Yeong-Min Park Diana Boraschi Seung-Hyun Han Chong-Su Cho Cheol-Heui Yun |
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Affiliation: | 1. Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea;2. World Class University Biomodulation Major & Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Republic of Korea;3. Brigham and Women’s Hospital & Harvard Medical School, Boston, MA 02115, USA;4. Laboratory Science Division, International Vaccine Institute, Seoul 151-919, Republic of Korea;5. Division of Life and Pharmaceutical Sciences, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Republic of Korea;6. Department of Immunology & Laboratory of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea;g Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P. Castellino111, 80131 Napoli, Italy;h Department of Oral Microbiology and Immunology & DRI, School of Dentistry, Seoul National University, Seoul 110-740, Republic of Korea |
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Abstract: | Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST. |
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Keywords: | Osmotically active polysorbitol transporter RSV glycoprotein Adjuvant activity Enhanced phagocytosis Long-term antibody response |
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