Peptide Amphiphile Micelles Self-Adjuvant Group A Streptococcal Vaccination

Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC16) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails. J8-diC16 formed cylindrical micelles with highly α-helical peptide presented on their surfaces. Both the micelle length and secondary structure were shown to be enhanced by annealing. When injected into mice, J8-diC16 micelles induced a strong IgG1 antibody response that was comparable to soluble J8 peptide supplemented with two classical adjuvants. It was discovered that micelle adjuvanticity requires the antigen be a part of the micelle since separation of J8 and the micelle was insufficient to induce an immune response. Additionally, the diC16 tail appears to be non-immunogenic since it does not stimulate a pathogen recognition receptor whose agonist (Pam3Cys) possesses a very similar chemical structure. The research presented in this paper demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.

[1]  Bo Yao,et al.  Conformational B-Cell Epitope Prediction on Antigen Protein Structures: A Review of Current Algorithms and Comparison with Common Binding Site Prediction Methods , 2013, PloS one.

[2]  M. Tirrell,et al.  Peptide contour length determines equilibrium secondary structure in protein-analogous micelles. , 2013, Biopolymers.

[3]  J. Corbett,et al.  Enhanced rat islet function and survival in vitro using a biomimetic self-assembled nanomatrix gel. , 2011, Tissue engineering. Part A.

[4]  Istvan Toth,et al.  Recent progress in adjuvant discovery for peptide-based subunit vaccines , 2014, Human vaccines & immunotherapeutics.

[5]  Y. Kuroda,et al.  Induction of lupus autoantibodies by adjuvants. , 2003, Journal of autoimmunity.

[6]  M. Skwarczynski,et al.  M-protein-derived conformational peptide epitope vaccine candidate against Group A Streptococcus. , 2013, Current drug delivery.

[7]  J. Carapetis,et al.  The global burden of group A streptococcal diseases. , 2005, The Lancet. Infectious diseases.

[8]  M. Tirrell,et al.  Internalization of p53(14-29) peptide amphiphiles and subsequent endosomal disruption results in SJSA-1 cell death. , 2010, Molecular pharmaceutics.

[9]  Matthew Tirrell,et al.  Self‐Assembled Peptide Amphiphile Micelles Containing a Cytotoxic T‐Cell Epitope Promote a Protective Immune Response In Vivo , 2012, Advanced materials.

[10]  Matthew Tirrell,et al.  Synthetic lipidation of peptides and amino acids: monolayer structure and properties. , 1995 .

[11]  Xiaoling Fu,et al.  Neural Progenitor Cells Survival and Neuronal Differentiation in Peptide-Based Hydrogels , 2011, Journal of biomaterials science. Polymer edition.

[12]  A. Middelberg,et al.  A microbial platform for rapid and low-cost virus-like particle and capsomere vaccines. , 2011, Vaccine.

[13]  G. Krivtsov,et al.  Chitosan as an adjuvant for poliovaccine , 2011, Journal of medical virology.

[14]  G. E. Macallum,et al.  Applications and optimization of immunization procedures. , 2005, ILAR journal.

[15]  S. Stupp,et al.  Induction of cancer cell death by self-assembling nanostructures incorporating a cytotoxic peptide. , 2010, Cancer research.

[16]  S. Stupp,et al.  Direct observation of morphological transformation from twisted ribbons into helical ribbons. , 2010, Journal of the American Chemical Society.

[17]  A. Nerlich,et al.  Variability in the Distribution of Genes Encoding Virulence Factors and Putative Extracellular Proteins of Streptococcus pyogenes in India, a Region with High Streptococcal Disease Burden, and Implication for Development of a Regional Multisubunit Vaccine , 2012, Clinical and Vaccine Immunology.

[18]  J. Carapetis,et al.  Group A streptococcal vaccines: facts versus fantasy , 2009, Current opinion in infectious diseases.

[19]  Corey Smith,et al.  A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. Passirani,et al.  Pegylated magnetic nanocarriers for doxorubicin delivery: a quantitative determination of stealthiness in vitro and in vivo. , 2012, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[21]  Joel H Collier,et al.  The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation. , 2013, Biomaterials.

[22]  Matthew Tirrell,et al.  Active targeting of early and mid-stage atherosclerotic plaques using self-assembled peptide amphiphile micelles. , 2014, Biomaterials.

[23]  S. Stupp,et al.  Self-assembling glucagon-like peptide 1-mimetic peptide amphiphiles for enhanced activity and proliferation of insulin-secreting cells. , 2012, Acta biomaterialia.

[24]  Erkki Ruoslahti,et al.  Targeting atherosclerosis by using modular, multifunctional micelles , 2009, Proceedings of the National Academy of Sciences.

[25]  Jangwook P. Jung,et al.  A self-assembling peptide acting as an immune adjuvant , 2009, Proceedings of the National Academy of Sciences.

[26]  R. Nagarajan,et al.  Molecular Packing Parameter and Surfactant Self-Assembly: The Neglected Role of the Surfactant Tail† , 2002 .

[27]  Matthew Tirrell,et al.  Wormlike micelle formation in peptide-lipid conjugates driven by secondary structure transformation of the headgroups. , 2009, The journal of physical chemistry. B.

[28]  U H Hansmann,et al.  Characteristic temperatures of folding of a small peptide. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Chun-Xia Zhao,et al.  Nanoparticle vaccines. , 2014, Vaccine.

[30]  J. Musser,et al.  New understanding of the group A Streptococcus pathogenesis cycle. , 2007, Trends in microbiology.

[31]  R. Bitton,et al.  Cooperative DNA binding and assembly by a bZip peptide-amphiphile , 2010 .

[32]  Samuel I Stupp,et al.  Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair , 2011, Proceedings of the National Academy of Sciences.

[33]  I. Toth,et al.  Development of a liposaccharide-based delivery system and its application to the design of group A streptococcal vaccines. , 2008, Journal of medicinal chemistry.

[34]  I. Toth,et al.  Immunological Evaluation of Lipopeptide Group A Streptococcus (GAS) Vaccine: Structure-Activity Relationship , 2012, PloS one.

[35]  Niklas Gloeckner,et al.  Vaccines For The 21st Century A Tool For Decision Making , 2016 .

[36]  R. Lawrence,et al.  Vaccines for the 21st Century , 2000 .

[37]  D. Narayanan,et al.  Synthesis, characterization and preliminary in vitro evaluation of PTH 1-34 loaded chitosan nanoparticles for osteoporosis. , 2012, Journal of biomedical nanotechnology.

[38]  V. Nizet,et al.  Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence , 2008, Science.

[39]  Manisha Pandey,et al.  Long-Term Antibody Memory Induced by Synthetic Peptide Vaccination Is Protective against Streptococcus pyogenes Infection and Is Independent of Memory T Cell Help , 2013, The Journal of Immunology.

[40]  John A. Robinson,et al.  Synthetic virus-like particles from self-assembling coiled-coil lipopeptides and their use in antigen display to the immune system. , 2007, Angewandte Chemie.

[41]  Xiaoyang Xu,et al.  Development of multinuclear polymeric nanoparticles as robust protein nanocarriers. , 2014, Angewandte Chemie.

[42]  S. Stupp,et al.  Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers. , 2011, Biomaterials.

[43]  R. Wyatt,et al.  Post-streptococcal acute glomerulonephritis in children: clinical features and pathogenesis , 2011, Pediatric Nephrology.

[44]  M. Good,et al.  Mapping the minimal murine T cell and B cell epitopes within a peptide vaccine candidate from the conserved region of the M protein of group A streptococcus. , 1997, International immunology.

[45]  A. Tekinay,et al.  Heparin mimetic peptide nanofibers promote angiogenesis. , 2011, Biomacromolecules.

[46]  N. Ketheesan,et al.  Induction of autoimmune valvulitis in Lewis rats following immunization with peptides from the conserved region of group A streptococcal M protein. , 2003, Journal of autoimmunity.

[47]  Flemming R Cassee,et al.  Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation , 2010, Particle and Fibre Toxicology.

[48]  Stuart R Stock,et al.  Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix. , 2010, Biomaterials.

[49]  E. Ruoslahti,et al.  Effect of the lipid chain melting transition on the stability of DSPE-PEG(2000) micelles. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[50]  Matthew Tirrell,et al.  Structural properties of soluble peptide amphiphile micelles , 2011 .

[51]  P. Yager,et al.  Protection of a Decapeptide from Proteolytic Cleavage by Lipidation and Self-Assembly into High-Axial-Ratio Microstructures: A Kinetic and Structural Study , 1999 .

[52]  Mei-Fong Ho,et al.  Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein. , 2006, The Journal of infectious diseases.

[53]  Matthew Tirrell,et al.  Mechanisms of peptide amphiphile internalization by SJSA-1 cells in vitro. , 2009, Biochemistry.

[54]  M. Tirrell,et al.  Advances in the design and delivery of peptide subunit vaccines with a focus on Toll-like receptor agonists , 2010, Expert review of vaccines.

[55]  R. Anders,et al.  Mapping a conserved conformational epitope from the M protein of group A streptococci. , 1996, Peptide research.

[56]  C. Liu,et al.  Persistent antigen at vaccination sites induces tumor-specific CD8+ T cell sequestration, dysfunction and deletion , 2013, Nature Medicine.

[57]  Tushar H. Gore,et al.  Self-Assembly of Model Collagen Peptide Amphiphiles , 2001 .

[58]  G. Lindahl,et al.  Extreme Sequence Divergence but Conserved Ligand-Binding Specificity in Streptococcus pyogenes M Protein , 2006, PLoS pathogens.

[59]  Manisha Pandey,et al.  Mechanism of Protection Induced by Group A Streptococcus Vaccine Candidate J8-DT: Contribution of B and T-Cells Towards Protection , 2009, PloS one.

[60]  S. Bellis,et al.  Osteogenic differentiation of human mesenchymal stem cells directed by extracellular matrix-mimicking ligands in a biomimetic self-assembled peptide amphiphile nanomatrix. , 2009, Biomacromolecules.

[61]  G. Fasman,et al.  Computed circular dichroism spectra for the evaluation of protein conformation. , 1969, Biochemistry.