Antigenic peptide nanofibers elicit adjuvant-free CD8⁺ T cell responses.

Vaccines that elicit robust CD8⁺ T cell responses are desirable for protection against infectious diseases and cancers. However, most vaccine adjuvants fail to elicit robust CD8⁺ T cell responses without inflammation and associated toxicity. We recently reported that self-assembling peptides that form nanofibers in physiological buffers elicited strong adjuvant-free and antigen-specific antibody responses in mice. However, whether or not such nanofibers likewise can elicit strong CD8⁺ T cell responses is unknown. Here, we demonstrate that the self-assembling peptide Q11 conjugated to a CD8⁺ T cell epitope of ovalbumin (Q11-OVA), elicits strong antigen-specific primary and recall responses, and in a vaccination regimen protects against subsequent infection. Importantly, we show that these antigenic peptide nanofibers do not persist as an inflammatory antigen depot at the injection site. Our results demonstrate for the first time that self-assembling peptides may be useful as carriers for vaccines where CD8⁺ T cell-mediated protection is needed.

[1]  N. Valiante,et al.  Recent advances in the discovery and delivery of vaccine adjuvants , 2003, Nature Reviews Drug Discovery.

[2]  W. van Eden,et al.  Considerations in the design of vaccines that induce CD8 T cell mediated immunity. , 2010, Vaccine.

[3]  R. Webby,et al.  Addition of a Prominent Epitope Affects Influenza A Virus-Specific CD8+ T Cell Immunodominance Hierarchies When Antigen Is Limiting1 , 2006, The Journal of Immunology.

[4]  Y. Kawaoka,et al.  Immunogenicity of a Recombinant Influenza Virus Bearing Both the CD4+ and CD8+ T Cell Epitopes of Ovalbumin , 2011, Journal of biomedicine & biotechnology.

[5]  S. Rosenberg,et al.  Cancer immunotherapy: moving beyond current vaccines , 2004, Nature Medicine.

[6]  R. Offringa,et al.  Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Kappler,et al.  Immune mechanisms of protection: can adjuvants rise to the challenge? , 2010, BMC Biology.

[8]  Joel H Collier,et al.  Modulating adaptive immune responses to peptide self-assemblies. , 2012, ACS nano.

[9]  S. Jameson,et al.  Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting. , 2013, Immunity.

[10]  Satish Mishra,et al.  Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope. , 2012, Biomaterials.

[11]  H. Pircher,et al.  T cell priming versus T cell tolerance induced by synthetic peptides , 1995, The Journal of experimental medicine.

[12]  Alan D. Roberts,et al.  The route of priming influences the ability of respiratory virus–specific memory CD8+ T cells to be activated by residual antigen , 2010, The Journal of experimental medicine.

[13]  J. Collier,et al.  A Self‐Adjuvanting Supramolecular Vaccine Carrying a Folded Protein Antigen , 2013, Advanced healthcare materials.

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

[15]  D. Bullard,et al.  Preferential Accumulation of Antigen-specific Effector CD4 T Cells at an Antigen Injection Site Involves CD62E-dependent Migration but Not Local Proliferation , 2003, The Journal of experimental medicine.

[16]  D. Cole,et al.  CD8+ T Cells Sabotage Their Own Memory Potential through IFN-γ–Dependent Modification of the IL-12/IL-15 Receptor α Axis on Dendritic Cells , 2012, The Journal of Immunology.

[17]  S. H. van der Burg,et al.  CD8+ CTL Priming by Exact Peptide Epitopes in Incomplete Freund’s Adjuvant Induces a Vanishing CTL Response, whereas Long Peptides Induce Sustained CTL Reactivity1 , 2007, The Journal of Immunology.

[18]  B. Nickoloff,et al.  Injection of pre-psoriatic skin with CD4+ T cells induces psoriasis. , 1999, The American journal of pathology.

[19]  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.

[20]  P. Thomas,et al.  NKG2D signaling on CD8+ T cells represses T-bet and rescues CD4-unhelped CD8+ T cell memory recall but not effector responses , 2011, Nature Medicine.

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

[22]  Jing-Wen Ma,et al.  A totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for cancer therapy. , 2012, Journal of the American Chemical Society.

[23]  M. Knuf,et al.  Comparative effects of carrier proteins on vaccine-induced immune response. , 2011, Vaccine.

[24]  M. Castrucci,et al.  Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection. , 2005, Virology.

[25]  H. Rammensee,et al.  Vaccination with minigenes encoding for novel 'self' antigens are effective in DNA-vaccination against neuroblastoma. , 2003, Cancer letters.

[26]  A. Zloza,et al.  Engagement of NK receptor NKG2D, but not 2B4, results in self-reactive CD8+T cells and autoimmune vitiligo , 2011, Autoimmunity.