tetano
Editor, Senior Moderator
Influenza A vaccines using linear expression cassettes delivered via electroporation afford full protection against challenge in a mouse model
Xuefei Shena,
Jonas S?derholmb,
Feng Lina,
Gary Kobingerc,
Alexander Belloc,
Derek A. Greggd,
Kate E. Brodericka, Corresponding author contact information, E-mail the corresponding author,
Niranjan Y. Sardesaia
a Inovio Pharmaceuticals, 1787 Sentry Parkway West, Blue Bell, PA 19422, United States
b Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
c Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
d Vandalia Research Inc., Huntington, WV 25701, United States
http://dx.doi.org/10.1016/j.vaccine.2012.02.071,
Abstract
Alternative DNA vaccine constructs such as fully synthetic linear expressing cassettes (LECs) offer the advantage of accelerated manufacturing techniques as well as the lack of both antibiotic resistance genes and bacterial contaminants. The speed of manufacture makes LEC technology a possible future vaccination strategy for pandemic influenza outbreaks. Previously, we reported on a novel concept of DNA delivery to dermal tissue by a minimally invasive electroporation (EP) surface device powered using low voltage parameters. This device allows electroporation without penetration of electrodes into the skin. In addition to enhancing the delivery of traditional plasmid DNA vaccines, this device may also offer a safe, tolerable and efficient method to administer LECs.
To assess immunogenicity and efficacy of EP-enhanced LEC delivery in mice, we designed and tested two influenza antigens in the form of LEC constructs delivered using the newly developed surface dermal EP device. Strong CTL and antibody responses were induced by the LEC versions of the DNA vaccine. When challenged with A/Canada/AB/RV1532/2009 viruses, mice immunized with LEC encoding the M2 and NP antigens recovered faster than na?ve or mice immunized ID without EP. Mice immunized with equal-molar doses of LEC encoding the M2 and NP antigens demonstrated 100% survival following a lethal (100? LD50) challenge of the heterologuos and highly pathogenic H5N1 influenza virus (A/Vietnam/1203/04).
These results suggest that influenza DNA vaccines based on LEC technology combined with the surface delivery platform are capable of fully protecting mice in a lethal challenge and the LEC based DNA constructs may serve as viable vaccine candidates.
Highlights
► LECs can induce immune responses which can be enhanced by surface electroporation. ► Levels of immune responses are comparable to responses induced by plasmid. ► Immune responses induced by NP and M2 LECs protect mice from influenza challenge.
http://www.sciencedirect.com/science/article/pii/S0264410X1200309X
Xuefei Shena,
Jonas S?derholmb,
Feng Lina,
Gary Kobingerc,
Alexander Belloc,
Derek A. Greggd,
Kate E. Brodericka, Corresponding author contact information, E-mail the corresponding author,
Niranjan Y. Sardesaia
a Inovio Pharmaceuticals, 1787 Sentry Parkway West, Blue Bell, PA 19422, United States
b Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
c Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
d Vandalia Research Inc., Huntington, WV 25701, United States
http://dx.doi.org/10.1016/j.vaccine.2012.02.071,
Abstract
Alternative DNA vaccine constructs such as fully synthetic linear expressing cassettes (LECs) offer the advantage of accelerated manufacturing techniques as well as the lack of both antibiotic resistance genes and bacterial contaminants. The speed of manufacture makes LEC technology a possible future vaccination strategy for pandemic influenza outbreaks. Previously, we reported on a novel concept of DNA delivery to dermal tissue by a minimally invasive electroporation (EP) surface device powered using low voltage parameters. This device allows electroporation without penetration of electrodes into the skin. In addition to enhancing the delivery of traditional plasmid DNA vaccines, this device may also offer a safe, tolerable and efficient method to administer LECs.
To assess immunogenicity and efficacy of EP-enhanced LEC delivery in mice, we designed and tested two influenza antigens in the form of LEC constructs delivered using the newly developed surface dermal EP device. Strong CTL and antibody responses were induced by the LEC versions of the DNA vaccine. When challenged with A/Canada/AB/RV1532/2009 viruses, mice immunized with LEC encoding the M2 and NP antigens recovered faster than na?ve or mice immunized ID without EP. Mice immunized with equal-molar doses of LEC encoding the M2 and NP antigens demonstrated 100% survival following a lethal (100? LD50) challenge of the heterologuos and highly pathogenic H5N1 influenza virus (A/Vietnam/1203/04).
These results suggest that influenza DNA vaccines based on LEC technology combined with the surface delivery platform are capable of fully protecting mice in a lethal challenge and the LEC based DNA constructs may serve as viable vaccine candidates.
Highlights
► LECs can induce immune responses which can be enhanced by surface electroporation. ► Levels of immune responses are comparable to responses induced by plasmid. ► Immune responses induced by NP and M2 LECs protect mice from influenza challenge.
http://www.sciencedirect.com/science/article/pii/S0264410X1200309X