TY - JOUR
T1 - Polymeric nanoengineered HBsAg DNA vaccine designed in combination with β‑glucan
AU - Soares, Edna
AU - Cordeiro, Rosemeyre
AU - Faneca, Henrique
AU - Borges, Olga
N1 - Funding Information:
This work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme [ CENTRO-01-0145-FEDER-000008:BrainHealth 2020 ] and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia , I.P. [ PROSAFE/0001/2016 ; POCI-01-0145-FEDER-007440 (UID/NEU/04539/2013) ; POCI-01-0145-FEDER-030331 ]. Edna Soares thanks FCT for PhD fellowship [DFRH - SFRH/BD/96167/2013], to Luisa Cortes and Margarida Caldeira from Microscopy Imaging Center of Coimbra (MICC-CNC) and to Daniel Gonçalves and Dra. Ana Donato from the Laboratory of Clinical Analysis of the Faculty of Pharmacy, University of Coimbra.
Funding Information:
This work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme [CENTRO-01-0145-FEDER-000008:BrainHealth 2020] and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, I.P. [PROSAFE/0001/2016; POCI-01-0145-FEDER-007440 (UID/NEU/04539/2013); POCI-01-0145-FEDER-030331]. Edna Soares thanks FCT for PhD fellowship [DFRH - SFRH/BD/96167/2013], to Luisa Cortes and Margarida Caldeira from Microscopy Imaging Center of Coimbra (MICC-CNC) and to Daniel Gonçalves and Dra. Ana Donato from the Laboratory of Clinical Analysis of the Faculty of Pharmacy, University of Coimbra.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Antigen-specific immune responses following DNA vaccination are hard to achieve, owing to the difficulty to mediate efficient gene delivery. This study proposed the use of PDMAEMA:PβAE/DNA polyplexes (Pol) as the vehicle of a pDNA vaccine encoding the hepatitis B surface antigen (HBsAg), with these Pol designed in combination with a soluble (Glu) or a particulate (GPs) form of β‑glucan. β‑Glucans are recognized adjuvants that activate immune cells, a good strategy to improve transfection efficiency and vaccine efficacy. Results showed that Pol produced at a 19:1 polymer:DNA (+/−) charge ratio were positively charged (+41 mV), had a mean size of 180 nm and presented high stability under different storage conditions. These polyplexes resulted in enhanced transfection activity than the positive control, showing even higher luciferase gene expression in the presence of GPs (COS-7 and RAW 264.7 cell lines). Additionally, no alterations in hemolysis and plasma coagulation time of human blood were found in the non-cytotoxic working range. Mice vaccination studies (pCMV-S), resulted in a seroconversion rate of 40%, regardless of the additional β‑glucan adjuvants. This work showed the potential of this nanosystem together with GPs to enhance in vitro transfection capacity and to be further studied as a DNA vaccination platform.
AB - Antigen-specific immune responses following DNA vaccination are hard to achieve, owing to the difficulty to mediate efficient gene delivery. This study proposed the use of PDMAEMA:PβAE/DNA polyplexes (Pol) as the vehicle of a pDNA vaccine encoding the hepatitis B surface antigen (HBsAg), with these Pol designed in combination with a soluble (Glu) or a particulate (GPs) form of β‑glucan. β‑Glucans are recognized adjuvants that activate immune cells, a good strategy to improve transfection efficiency and vaccine efficacy. Results showed that Pol produced at a 19:1 polymer:DNA (+/−) charge ratio were positively charged (+41 mV), had a mean size of 180 nm and presented high stability under different storage conditions. These polyplexes resulted in enhanced transfection activity than the positive control, showing even higher luciferase gene expression in the presence of GPs (COS-7 and RAW 264.7 cell lines). Additionally, no alterations in hemolysis and plasma coagulation time of human blood were found in the non-cytotoxic working range. Mice vaccination studies (pCMV-S), resulted in a seroconversion rate of 40%, regardless of the additional β‑glucan adjuvants. This work showed the potential of this nanosystem together with GPs to enhance in vitro transfection capacity and to be further studied as a DNA vaccination platform.
KW - DNA HBsAg
KW - PDMAEMA:PβAE
KW - β‑Glucan
UR - http://www.scopus.com/inward/record.url?scp=85056254607&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2018.11.024
DO - 10.1016/j.ijbiomac.2018.11.024
M3 - Article
C2 - 30412757
AN - SCOPUS:85056254607
SN - 0141-8130
VL - 122
SP - 930
EP - 939
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -
