Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines.
Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(ortho esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.
Department of Chemical Engineering, E25-342, 77 Mass. Ave., Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Chun
C
Wang
Qing
Q
Ge
David
D
Ting
David
D
Nguyen
Hui-Rong
HR
Shen
Jianzhu
J
Chen
Herman N
HN
Eisen
Jorge
J
Heller
Robert
R
Langer
David
D
Putnam
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology*; D008863:Microspheres; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D004952:Esters; D019444:Vaccines, DNA