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Acinetobacter baumannii often causes serious nosocomial infections. Because of its serious drug resistance problems, complex drug resistance mechanism, and rapid adaptation to antibiotics, it often shows pan-drug resistance and high fatality rates, which represent great challenges for clinical treatment. Therefore, identifying new ways to overcome antibiotic resistance is particularly important. In this study, mice immunized with A. baumannii outer membrane vesicles (AbOMVs) produced high IgG levels for a long time, and this antiserum significantly increased the small molecule intracellular aggregation rate and concentrations. In vitro experiments demonstrated that the combined used of anti-AbOMV serum and quinolone antibiotics significantly increased the sensitivity of the bacteria to these antibiotics. Mouse sepsis model experiments demonstrated that delivery of these antibodies using both active and passive immunization strategies significantly improved the susceptibility to quinolone antibiotics, improved the survival rate of mice infected with A. baumannii , and reduced the bacterial load in the organs. In a pneumonia model, the combination of serum anti-AbOMVs and levofloxacin improved levofloxacin sensitivity, which significantly reduced the bacterial loads in the lung and spleen compared with those of the antibiotic or antibody alone. This combination also significantly reduced lung inflammatory cell infiltration and inflammatory cytokine aggregation. In this study, the main protein targets that bound to these antibodies were identified. Structural modeling showed that seven of the proteins were porins. Therefore, we speculated that the anti-AbOMV antibodies mainly improved the intracellular aggregation of antibiotics by affecting porins, thus improving susceptibility to quinolone antibiotics. This study provides a method to improve susceptibility to existing antibiotics and a novel idea for the prevention and treatment of pan-drug-resistant A. baumannii .

BackgroundVaccines are one of the most promising strategies for immunotherapy of HPV associated tumors; however, they generally lack significant clinical efficacy at present. This inefficacy might be due to inefficient generation of anti-tumor cellular immune responses.PurposeThis study aimed to assess the potential of using self-assembled nanofibers as a new vaccine platform to elicit potent HPV antigen - specific anti-tumor immunity.MethodsA HPV16 E744-62 peptide was chemically appended to the N terminus of self-assembling peptide Q11. The nanofibers were prepared and used to immunize mice through a preventive or therapeutic strategy in a TC-1 graft tumor model.ResultsPreventive immunization with nanofibers almost completely suppressed the growth of primarily grafted TC-1 tumors and even a re-challenge of tumor cells after a six-week rest. Therapeutic immunization significantly increased the levels of effector Th1 cells, CTLs and the cytokines IFN-γ and TNF-α in E7 peptide-stimulated splenocytes, and the immunization reduced Th2, MDSC and IL-4 contents compared to the controls. The nanofiber immunization significantly suppressed the growth of established tumors and achieved 66.7% and 50% tumor-free in mice carrying 2–3 mm tumors and even larger tumors with a diameter of 5–6 mm respectively. In addition, the nanofibers were more efficient than the corresponding unassembled peptides for the treatment of established larger size tumors.ConclusionThe results indicated that self-assembling nanofibers could elicit robust HPV antigen -specific anti-tumor cellular immunity and are a potent antigen delivery system for HPV related tumor vaccines.

Background: Fibroblast growth factor (FGF)-2 is overexpressed in various tumor tissues. It affects tumor cell proliferation, invasion and survival, promotes tumor angiogenesis and is tightly involved in the development of systemic and local immunosuppressive tumor mechanisms. Purpose: This study aimed to develop an effective vaccine against FGF-2 and to investigate the effects of anti-FGF-2 immunization on tumor growth and antitumor immune responses. Methods: A set of thirteen synthesized overlapping peptides covering all possible linear B-cell epitopes of murine FGF-2 and a recombinant FGF-2 protein were conjugated to viruslike particles (VLPs) of recombinant hepatitis B core antigen (HBcAg). The VLPs were immunized through a preventive or therapeutic strategy in a TC-1 or 4T1 grafted tumor model. Results: Immunization with FGF-2 peptides or full-length protein-coupled VLPs produced FGF-2-specific antibodies with a high titer. Peptide 12, which is located in the heparin-binding site of FGF-2, or protein-conjugated VLPs presented the most significant effects on the suppression of TC-1 tumor growth. The levels of IFN-γ-expressing splenocytes and serum IFN-γ were significantly elevated; further, the immune effector cells CD8 + IFN-γ + cytotoxic T lymphocytes (CTLs) and CD4 + IFN-γ + Th1 cells were significantly increased, whereas the immunosuppressive cells CD4 + CD25 + FOXP3 + Treg cells and Gr-1 + CD11b + myeloidderived suppressor cells (MDSCs) were decreased in the immunized mice. In addition, VLP immunization significantly suppressed tumor vascularization and promoted tumor cell apoptosis. In mice bearing 4T1 breast tumor, preventive immunization with FGF-2-conjugated VLPs suppressed tumor growth and lung metastasis, and increased effector cell responses. Conclusion: Active immunization against FGF-2 is a new possible strategy for tumor immunotherapy.

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