Synergy effects of Polyinosinic-polycytidylic acid, CpG oligodeoxynucleotide, and cationic peptides to adjuvant HPV E7 epitope vaccine through preventive and therapeutic immunization in a TC-1 grafted mouse model

Cross-talk by pattern recognition receptors may facilitate the maturation of dendritic cells and fine tune the immune response. Thus, the inclusion of ligands agonistic to multiple receptors in a vaccine formula may be an effective strategy to elicit robust antitumor cellular immunity. We tested the adjuvant effects and possible synergy of CpG (CpG oligodeoxynucleotide), Poly I:C (polyinosinic-polycytidylic acid) and the cationic peptide Cramp (cathelicidin-related antimicrobial peptide) formulated in a DOTAP (1,2-dioleoyl-3-trimethylammonium-propane) liposomal HPV E7 epitope vaccine on a TC-1 grafted mouse model. The vaccine formulations were administered both preventively and therapeutically. Based on our results, both CpG and Poly I:C-adjuvanted vaccines abolished tumor development in a preventive trial and significantly suppressed tumor growth in a therapeutic trial. Increased interferon (IFN)-γ expression and potent memory T cells in splenocytes as well as elevated CD8+IFN-γ+ cells in both spleen and tumor tissue indicated an elevated E744-62-specific cellular immune response. Although synergistic effects were detected between CpG and Poly I:C, their adjuvant effects were not enhanced further when combined with Cramp. Because the enhancement of tumor antigen-specific cellular immune responses is vital for the clearance of infected and cancerous cells, our results contribute a potential adjuvant combination for cancer vaccines

The sedimentary succession of the last 2.25 Myr in the Bohai Strait: Implications for the Quaternary paleoenvironmental evolution of the Bohai Sea

The Bohai Strait connects the Bohai Sea with the Yellow Sea, allowing material and energy exchange between the seas. The sedimentary record in this region is important for reconstructing the Quaternary sea-level changes and environmental evolution in the Bohai Sea area; however, long sedimentary sequences with a reliable chronological framework from this area are scarce. We assessed the sedimentary characteristics, grain size, microfossils, accelerator mass spectrometry 14C ages and optically stimulated luminescence ages of core BHS01 from the Bohai Strait. From these and previous paleomagnetic results, new insights into regional sea-level changes and environmental evolution in the Bohai Strait over the last 2.25 Myr are obtained. The sedimentology and environmental proxies (benthic foraminifera and marine ostracods) indicate that the sedimentary environment of the area around core BHS01 was mainly dominated by fluvial-lacustrine deposits from 2.25 to 0.89 Ma, and subsequently by alternating marine and fluvial deposits. Comparative analyses of the chronological and sedimentary results of core BHS01 with previous drilling records in the eastern marginal seas of China revealed that the Quaternary initial marine transgression of the Bohai Sea occurred no later than 0.89 Ma (latest early Pleistocene) since Quaternary. The initial transgression presumably resulted from the partial subsidence and disintegration of the Miaodao Islands Uplift with sea-level rise during this period or slightly earlier. This result is generally consistent with the timing of the Quaternary regional marine transgressive processes of the Yellow and Bohai seas; thus, we propose a conceptual model in which the first marine transgression of the Yellow Sea and the Bohai Sea during the Quaternary occurred no later than 1.66 Ma and 0.89 Ma, respectively. This study provides new evidence for understanding the Quaternary sea-level changes and regional environmental evolution in the Bohai Sea