A combination of intradermal jet-injection and electroporation overcomes in vivo dose restriction of DNA vaccines

نویسندگان

  • David Hallengärd
  • Andreas Bråve
  • Maria Isaguliants
  • Pontus Blomberg
  • Jenny Enger
  • Richard Stout
  • Alan King
  • Britta Wahren
چکیده

UNLABELLED BACKGROUND The use of optimized delivery devices has been shown to enhance the potency of DNA vaccines. However, further optimization of DNA vaccine delivery is needed for this vaccine modality to ultimately be efficacious in humans. METHODS Herein we evaluated antigen expression and immunogenicity after intradermal delivery of different doses of DNA vaccines by needle or by the Biojector jet-injection device, with or without the addition of electroporation (EP). RESULTS Neither needle injection augmented by EP nor Biojector alone could induce higher magnitudes of immune responses after immunizations with a high dose of DNA. After division of a defined DNA dose into multiple skin sites, the humoral response was particularly enhanced by Biojector while cellular responses were particularly enhanced by EP. Furthermore, a close correlation between in vivo antigen expression and cell-mediated as well as humoral immune responses was observed. CONCLUSIONS These results show that two optimized DNA vaccine delivery devices can act together to overcome dose restrictions of plasmid DNA vaccines.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Genetic Vaccines and Therapy

Background: The use of optimized delivery devices has been shown to enhance the potency of DNA vaccines. However, further optimization of DNA vaccine delivery is needed for this vaccine modality to ultimately be efficacious in humans. Methods: Herein we evaluated antigen expression and immunogenicity after intradermal delivery of different doses of DNA vaccines by needle or by the Biojector jet...

متن کامل

DNA-Based Vaccine Is More Efficient than Non-Pathogenic Live Vaccine for the Prevention of HPV16 E7-Overexpressing Cancers

  Introduction: Vaccinology provides promising approaches for the control of various infectious diseases. Among different strategies, DNA vaccines offer attractive research opportunities for development of vaccines for induction of antigen-specific immunity owing to their stability, simplicity of delivery, safety and cost effectiveness. However, there is a need to increase their potency by the ...

متن کامل

Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation.

Recently it has become clear that more potent methods for DNA vaccine delivery need to be developed to enhance the efficacy of DNA vaccines. In vivo electroporation has emerged as a potent method for DNA vaccine delivery. In a mouse model, we evaluated the CD8(+) T lymphocyte response to a prostate cancer DNA vaccine encoding prostate-specific antigen (PSA) after intradermal electroporation. A ...

متن کامل

A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin

The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This article describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluo...

متن کامل

Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice.

Intramuscular injection of DNA vaccines elicits potent humoral and cellular immune responses in mice. However, DNA vaccines are less efficient in larger animal models and humans. To gain a better understanding of the factors limiting the efficacy of DNA vaccines, we used fluorescence-labeled plasmid DNA in mice to 1) define the macroscopic and microscopic distribution of DNA after injection int...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 10  شماره 

صفحات  -

تاریخ انتشار 2012