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Issue 7, 2011
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pH-responsive polymer–antigen vaccine bioconjugates

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Abstract

Protein-based vaccines play an important role in controlling infectious disease but their full clinical impact has been limited by their inability to generate a coordinated cellular CD4+ and CD8+ immune response. Vaccines that better deliver antigens to the cytosolic MHC1 display system could in principle provide a better coordinated response. Here, controlled radical polymerization was employed to prepare a diblock copolymer containing an endosomal releasing segment based on poly(propylacrylic acid) (poly(PAA)) and a hydrophilic segment containing thiol-reactive disulfide moieties for antigen conjugation. Propylacrylic acid (PAA) was polymerized in the presence of a trithiocarbonate based RAFT chain transfer agent (CTA). The resultant poly(PAA) was then employed as a macroCTA in the copolymerization of pyridyl disulfide methacrylamide (PDSMA) (thiol-reactive monomer) and N,N-dimethylacrylamide (DMA) as a hydrophilic comonomer. Copolymer compositions and molecular weights were determined via1H NMR spectroscopy and size exclusion chromatography. Native polyacrylamide gel electrophoresis (PAGE) showed a complete disappearance of the bands corresponding to free thiolated ovalbumin after conjugation to the polymer at pyridyl disulfide to thiol ratios as low as 2.5. The ability of the poly[(PAA)-b-(DMA)co(PDSMA)]–ovalbumin conjugates to activate CTLs was evaluated in vivo, tumor protection using the EG7 tumor protection model. Tumors were visible in the PBS and free ovalbumin immunized mice by day 7 but were not visible in the polyPAA–ovalbumin conjugate immunized mice until day 18. The mice immunized with the polyPAA–ovalbumin conjugate had a survival rate at day 21 of 100% versus 20% for PBS and 40% for ovalbumin immunized mice.

Graphical abstract: pH-responsive polymer–antigen vaccine bioconjugates

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Article information


Submitted
03 Feb 2011
Accepted
14 Mar 2011
First published
18 May 2011

Polym. Chem., 2011,2, 1499-1504
Article type
Paper

pH-responsive polymerantigen vaccine bioconjugates

E. F. Crownover, A. J. Convertine and P. S. Stayton, Polym. Chem., 2011, 2, 1499 DOI: 10.1039/C1PY00060H

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