The Eleventh Korea-U.S. Forum on Nanotechnology
Induction of Long-Term Immunity Against
Respiratory Syncytial Virus Glycoprotein by An
Osmotic Polymeric Nanocarrier
Jannatul Firdous, Ph.D. candidate
Laboratory of Immunology and Vaccine Development
College of Agriculture and Life Sciences
Seoul National University
Vaccine adjuvant & Delivery system
Immunology and
Vaccine Development
Seoul Nat’l Univ.
Advanced approaches
Nanoparticles – novel concept
Licensed adjuvant for human vaccine
Alum;
2006 Nov;24(11):1377-83.
AS04 (Alum+MPL);
MF59 and AS03
1.
2.
3.
4.
Adjuvant
Physical chemistry
Safety
Cellular Uptake and release
Antibody response >> Long term persistency
September 29-30, 2014
PST
2
Previous
Hypothesisstudies from our group
Immunology and
Vaccine Development
Seoul Nat’l Univ.
PSOAT: polysorbitol-based osmotically active transporter
Intranasal delivery of
nanocomplexes (PST/RGp)
Long-term persistency of
antibody
Dr. Mohammad Ariful Islam
Immune cellular uptake
>200 Days
1. Design of PSOAT to Regulate Cellular Pathways
(Islam et al., Biomaterials, 2011; IF: 8.312)
2. Function of PSOAT in RNAi Silencing
3. Therapeutic of PSOAT inRGp-specific
RNAi Silencing
antibody
PST: Poly Sorbitol Transporter
September 29-30, 2014
RGp: Respiratory Syncytial Virus
Glycoprotein
(Islam et al., Biomaterials, 2012; IF: 8.312)
(Islam et al., Biomaterials, 2013; IF: 8.312)
Phagocytic cells
RGp-specific antibody
3
PST as novel and safe nano-adjuvant
1. Physical chemistry
2. Safety
3. Cellular uptake and release
Immunology and
Vaccine Development
Seoul Nat’l Univ.
4. Ab response
Entirely non-toxic compared to Cholera Toxin (CT)
PBS
Polysorbitol
transporter
(PST)
Osmoticallyactive
PST/RGp
complexes
PST (100 µg)
PST (250 µg)
CT (2 µg)
CT (10 µg)
Phagolysosomal escape in macrophage by proton sponge effect of PEI
Selectivity toward
phagocytes due to osmotic
4h
0.5 h
Enhanced activation of phagocytes
microenvironment
(e.g. macrophage surface)
(e.g. Macrophage)
(i) Phagocytosis
(ii) Inside phagosome
5h
RSV G protein
(RGp)
RAW264.7
(iv) In cytosol
A549
(iii) Proton
sponge
effect
FITC-PST/RGp
Day 203
Routinely intra-nasal
vaccine delivery
PST
RGp
September 29-30, 2014
RGp-specific ab response
Phagocytic cells
Long-term persistency
Non-phagocytic cells
Antibody secreting cells
RGp-specific antibody
4
PST as novel and safe nano-adjuvant
1. Physical chemistry
2. Safety
3. Cellular uptake and release
Immunology and
Vaccine Development
Seoul Nat’l Univ.
4. Ab response
Entirely non-toxic compared to Cholera Toxin (CT)
PBS
Polysorbitol
transporter
(PST)
Osmoticallyactive
PST/RGp
complexes
PST (100 µg)
PST (250 µg)
CT (2 µg)
CT (10 µg)
Phagolysosomal escape in macrophage by proton sponge effect of PEI
Selectivity toward
phagocytes due to osmotic
4h
0.5 h
Enhanced activation of phagocytes
microenvironment
(e.g. macrophage surface)
(e.g. Macrophage)
(i) Phagocytosis
(ii) Inside phagosome
5h
RSV G protein
(RGp)
RAW264.7
(iv) In cytosol
A549
(iii) Proton
sponge
effect
FITC-PST/RGp
Day 203
Routinely intra-nasal
vaccine delivery
PST
RGp
September 29-30, 2014
RGp-specific ab response
Phagocytic cells
Long-term persistency
Non-phagocytic cells
Antibody secreting cells
RGp-specific antibody
5
PST as novel and safe nano-adjuvant
1. Physical chemistry
2. Safety
3. Cellular uptake and release
Immunology and
Vaccine Development
4. Ab response
Seoul Nat’l Univ.
Entirely non-toxic compared to Cholera Toxin (CT)
PBS
Polysorbitol
transporter
(PST)
Osmoticallyactive
PST/RGp
complexes
PST (100 µg)
PST (250 µg)
CT (2 µg)
CT (10 µg)
Phagolysosomal escape in macrophage by proton sponge effect of PEI
Selectivity toward
phagocytes due to osmotic
4h
0.5 h
Enhanced activation of phagocytes
microenvironment
(e.g. macrophage surface)
(e.g. Macrophage)
(i) Phagocytosis
(ii) Inside phagosome
5h
RSV G protein
(RGp)
RAW264.7
(iv) In cytosol
A549
(iii) Proton
sponge
effect
FITC-PST/RGp
Day 203
Routinely intra-nasal
vaccine delivery
PST
RGp
September 29-30, 2014
RGp-specific ab response
Phagocytic cells
Long-term persistency
Non-phagocytic cells
Antibody secreting cells
RGp-specific antibody
6
PST as novel and safe nano-adjuvant
1. Physical chemistry
2. Safety
3. Cellular uptake and release
Immunology and
Vaccine Development
4. Ab response
Seoul Nat’l Univ.
Entirely non-toxic compared to Cholera Toxin (CT)
PBS
Polysorbitol
transporter
(PST)
Osmoticallyactive
PST/RGp
complexes
PST (100 µg)
PST (250 µg)
CT (2 µg)
CT (10 µg)
Phagolysosomal escape in macrophage by proton sponge effect of PEI
Selectivity toward
phagocytes due to osmotic
4h
0.5 h
Enhanced activation of phagocytes
microenvironment
(e.g. macrophage surface)
(e.g. Macrophage)
(i) Phagocytosis
(ii) Inside phagosome
5h
RSV G protein
(RGp)
RAW264.7
(iv) In cytosol
A549
(iii) Proton
sponge
effect
FITC-PST/RGp
Accepted in ‘Acta Biomateriala’ on
31st July, 2014; Impact Factor: 5.684
Day 203
Routinely intra-nasal
vaccine delivery
PST
RGp
September 29-30, 2014
RGp-specific ab response
Phagocytic cells
Long-term persistency
Non-phagocytic cells
Antibody secreting cells
RGp-specific antibody
7
Acknowledgments
Supervised By: Prof. Cheol Heui YUN
Immunology and Vaccine Development Lab.
Immunology and
Vaccine Development
Seoul Nat’l Univ.
Collaborations and Contributions
Prof. Chong-Su Cho, Korea
Prof. Seung-Hyun Han, Korea
서울대학교
Seoul National
University
Dr. Diana Boraschi, Italy
Dr. Mohammad Ariful Islam, USA
Thank you
September 29-30, 2014
8