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.
Wang
Chun
C
Department of Chemical Engineering, E25-342, 77 Mass. Ave., Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Ge
Qing
Q
Ting
David
D
Nguyen
David
D
Shen
Hui-Rong
HR
Chen
Jianzhu
J
Eisen
Herman N
HN
Heller
Jorge
J
Langer
Robert
R
Putnam
David
D
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