Mouse Anti-M13 monoclonal antibody, clone NN16

Immune tolerance is the main challenge in the field of cancer vaccines, so modified peptide sequences or naturally occurring mutated versions of cancer-related wild-type (WT) antigens represent a promising pathway. However, the low immunogenicity of mutation-induced neoantigens and, particularly, their incapacity to activate CD8(+)T cells are generating doubts on the success of neoantigen-based cancer vaccines in clinical trials. We developed a novel vaccine approach based on a new class of vaccine immunogens, called variable epitope libraries (VELs). We used three regions of survivin (SVN), composed of 40, 49 and 51 amino acids, along with the complete SVN protein to generate the VELs as multiepitope vaccines. BALB/c mice, challenged with the aggressive and highly metastatic 4T1 cell line, were vaccinated in a therapeutic setting. We showed significant tumor growth inhibition and, most importantly, strong suppression of lung metastasis after a single immunization using VEL vaccines. We demonstrated vaccine-induced broad cellular immune responses concomitant with extensive tumor infiltration of T cells, the activation of CD107a(+) IFN-gamma T+ cells in the spleen and a significant increase in the number of CD3(+) CD8(+) Ly6C(+)effector T cells. In addition, we observed the presence of interferon-gamma-, granzyme B- and perforin-producing lymphocytes along with modifications in the amount of CD11b(+) Ly6C(int/low) Ly6G(+)granulocytic myeloid-derived suppressor cells and CD4(+) CD25(+) FoxP3(+)regulatory T cells in the lungs and tumors of mice. In summary, we showed that the VELs represent a potent new class of cancer immunotherapy and propose the application of the VEL vaccine concept as a true alternative to currently available vaccine platforms.

An optical and colorimetric biosensor comprising gold nanowires (Au NWs) templated with genetically engineered M13 bacteriophages expressing a specific Au binding peptides tyrosine-glutamic acid-glutamic acid-glutamic acid (Y3E) is fabricated by silver nitrate and surfactant-mediated biomineralization process. The diameter of the Y3E-Au NWs is around 10 nm and an oriented growth mechanism is identified for the continuous growth of the NWs by interconnecting M13 bacteriophages. The flexible Au NWs have formed an enriched Hg(II) binding sites on its surface and the surface-coated silver nanophase functions as a receptor for more efficient Hg (II) binding. Amalgamation-based colorimetric and optical Hg(II) biosensing of Au NWs are scrutinized in the presence of wild-type M13 bacteriophage-templated Au NWs and spherical Au nanoparticles. It is demonstrated that in comparison with the spherical Au nanoparticles, Y3E-Au NWs exhibits an aggregation-free optical and colorimetric sensor for Hg(II). Mechanistic investigation for the aggregation-free sensor and the Au-Hg amalgam crystals are carried out using TEM, STEM-EDX and XPS analyses.