Numerous vaccines have been developed to address the current COVID-19 pandemic, but safety, cross-neutralizing efficacy, and long-term protectivity of currently approved vaccines are still important issues. In this study, we developed a subunit vaccine, ASD254, by using a nanoparticle vaccine platform to encapsulate the SARS-CoV-2 spike receptor-binding domain (RBD) protein. As compared with the aluminum-adjuvant RBD vaccine, ASD254 induced higher titers of RBD-specific antibodies and generated 10- to 30-fold more neutralizing antibodies. Mice vaccinated with ASD254 showed protective immune responses against SARS-CoV-2 challenge, with undetectable infectious viral loads and reduced typical lesions in lung. Besides, neutralizing antibodies in vaccinated mice lasted for at least one year and were effective against various SARS-CoV-2 variants of concern, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, particle size, polydispersity index, and zeta-potential of ASD254 remained stable after 8-month storage at 4°C. Thus, ASD254 is a promising nanoparticle vaccine with good immunogenicity and stability to be developed as an effective vaccine option in controlling upcoming waves of COVID-19.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.

The emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals receiving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a “Hybrid” vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specific RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.

With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance.

Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets. We first validate cleavage at a putative furin substrate motif at SARS-CoV-2 spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage and the syncytium are abolished by treatment with the furin inhibitors decanoyl-RVKR-chloromethylketone (CMK) and naphthofluorescein, but not by the transmembrane protease serine 2 (TMPRSS2) inhibitor camostat. CMK and naphthofluorescein show antiviral effects on SARS-CoV-2-infected cells by decreasing virus production and cytopathic effects. Further analysis reveals that, similar to camostat, CMK blocks virus entry, but it further suppresses cleavage of spikes and the syncytium. Naphthofluorescein acts primarily by suppressing viral RNA transcription. Therefore, furin inhibitors may be promising antiviral agents for prevention and treatment of SARS-CoV-2 infection.

Abstract The goal of cancer immunotherapy is to elicit robust tumor-specific immune responses that can generate durable tumor regression and/or eradication. Recent clinical trials using immune checkpoint blockades specific to programmed cell death-1/ligand-1 (PD-1/PD-L1) have shown durable clinical responses in various cancer types but benefit only a small portion of patients. We previously demonstrated that combination of radiation and immunotherapy of interleukin 12 (IL-12) and granulocyte macrophage colony-stimulator factor (GM-CSF) greatly improved the therapeutic efficacy than either single therapy alone. In analysis of the tumor-infiltrating leukocytes post combination therapy, we found that the number of CD11b+F4/80-/Ly6G+ neutrophils were greatly increased. In this study, we characterized these tumor-associated neutrophils (TANs) before and after treatment and investigated their role in mediating the antitumor activity of the combination therapy. We isolated TANs from the regressing tumors and demonstrated that these TANs were impaired in their immunosuppressive activities. Flowcytometric analysis revealed that several co-stimulatory molecules, including class II major histocompatibility complex, CD40 and CD86, were increased on these TANs. Accordingly, these TANs gained the ability to stimulate T cell proliferation. Antibody-depletion experiments showed that TANs were required for tumor regression in RT/12GM combination therapy. Together, our data demonstrate that combination of radiotherapy and IL-12/GM-CSF improved antitumor immunity through enhancing antigen presentation activity and reduced immunosuppressive functions of TANs. Citation Format: Mi-Hua Tao, Chia-Jen Wu, Yi-Ting Tsai, Ping-Yi Wu. Neutrophils play a critical role in mediating antitumor activity of a combination therapy of radiation and immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 609.

Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment within a well-established orthotopic HCC toward a state favorable for inducing antitumor immunities. Our data showed that radiation and IL-12 combination therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large subcutaneous or orthotopic HCC, induced systemic effect against distant tumor, and significantly prolonged survival. Radiation monotherapy induced tumor regression at early times but afterwards most tumors regained exponential growth, while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules CD40 and CD86 on tumor-infiltrating dendritic cells, suggesting an improvement of their antigen presentation activity. RT/IL-12 also significantly reduced accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and impaired their suppressive functions by reducing production of reactive oxygen species. Accordingly, tumor-infiltrating CD8+ T cells and NK cells were significantly activated toward the antitumor phenotype, as revealed by increased expression of CD107a and TNF-α. Together, our data showed that RT/IL-12 treatment could reset the intratumoral immunotolerant state and stimulate activation of antitumor cellular immunity that is capable of eliminating large established HCC tumors.

Interleukin-21 is a pleiotropic cytokine which has shown promising antitumor activities in several preclinical models but the response rate in phase I–II clinical studies has been disappointing. Therefore, the optimal usage of IL-21 as an effective therapy against cancers remains to be studied. Radiotherapy, a well establish treatment modality for cancers, has shown its potential in immunogenic modulation by stimulating immune cell phagocytosis and inducing local tumor-associated antigens releasing. We hypothesize that a synergistic antitumor effect could be achieved by combining IL-21 with radiation through releasing neoantigens and amplifying adaptive antitumor immune responses against both primary and metastatic tumors. We treated mice bearing large established tumors with radiation, IL-21 or a combination of radiation and IL-21. Mice treated with radiation alone showed delayed tumor growth, while IL-21 treatment had very little effect. In contrast, a synergistic antitumor effect was achieved in the combination group, which not only led to complete tumor regression of primary tumors, but also significantly suppressed the growth of distant, untreated metastatic tumors. Mechanistic analysis revealed that combination therapy increased accumulation of tumor-infiltrating CD8+ T cells which showed enhanced functional activities, marked by increased expression of CD107a, IFN-γ and TNF-α. Moreover, mice that had been cured by the combination therapy developed memory responses against the subsequent tumor re-challenge. Our results demonstrate that combination of IL-21 and radiation has potent antitumor activity against both primary and metastatic tumors and could open a new perspective for cancer therapy.

Immune checkpoint blockade antibodies specific to programed death-1/ligand-1 (PD-1/PD-L1) shows durable clinical responses in various cancers but benefit only to a small portion of patients. The failure of immunotherapy is likely due to the complex network of immunosuppressive mechanisms present in advanced tumors. Radiation (RT) modifies tumor microenvironment and causes tumor antigen release, and thus augment efficacy of immunotherapy. Interleukin 12 (IL-12) and granulocyte macrophage colony-stimulator factor (GM-CSF) have shown potent antitumor activities through activating innate and adaptive immunities, as well as reprogramming myeloid cells to a phenotype that favors immune activation. The aim of this project is to compare the therapeutic efficacy of two types of combination therapy: RT combined with IL-12/GM-CSF (RT/12GM) versus RT combined with anti-PD-L1 antibody (RT/PD-L1), and to dissect the molecular mechanisms of the antitumor responses. Our data showed that RT/12GM led to tumor regression in a majority of mice with large established tumors and suppressed liver metastasis, while RT/PD-L1 could only suppress primary tumors but not metastatic tumor. Mechanistic analysis showed that RT/12GM was superior to RT/PD-L1 in inducing accumulation of CD8+ T cells in tumor and in augmenting both NK and CD8+ T cells cytotoxicity in tumor and liver. Interestingly, RT/12GM also induced infiltration of tumor-associated neutrophils (TAN) and impaired their immunosuppressive functions. Depletion experiments showed that both CD8+ T cell and TAN were required for tumor regression in RT/12GM. Together, our results demonstrate that RT/12GM represent a powerful alternative therapy against both primary and metastatic tumors.

Hepatitis B virus (HBV) infection causes severe public health problem. There are estimated 250 million people being chronically infected by HBV and are at an increased risk of developing end-stage liver diseases, such as cirrhosis and hepatocellular carcinoma. It is well recognized that the chronicity of HBV infection is due to the impaired immune responses to HBV and thus not able to eliminate HBV from the infected hepatocytes. However, the immune mechanisms that lead to immune tolerance and HBV persistence have not been understood. A challenging question for HBV studies is lack of appropriate animal models due to the narrow host range of HBV. To address this challenge, we created a chronic HBV infection model in immunocompetent mice by transduction of adeno-associated virus serotype 8 (AAV8) vector which carries and these mice was transduced with carrying a replication-defective HBV genome with two point mutations in the polymerase(AAV/HBVp−). We showed that mice transduced with AAV/HBVp− produced HBV RNA and proteins, including serum HBV surface antigen and HBV e antigen as well as HBV core protein. The high levels of HBV RNA and proteins sustained for at least 1 year post AAV transduction. Viral transcripts and proteins were detected in the livers of the AAV-injected mice but not in other organs. DNA immunization of these AAV/HBVp− transduced mice failed to induce HBV-specific humoral and cellular immune responses, suggesting these mice developed immune tolerance toward HBV. Thus, the AAV/HBVp− transduced mouse model recapitulates many virological and immunological characteristics of chronic HBV in humans. This animal model could be useful for the development of new treatments and immune-based therapies for chronic HBV infections.

Cancer immunotherapy can elicit robust tumor-specific immune responses that can generate durable tumor regression or eradication. Immune checkpoint blockade specific to programmed death-1/ligand-1 (PD1/PDL1) have shown durable clinical responses in various cancer types but benefit only a small portion of patients. Interleukin 12 (IL-12) and granulocyte macrophage colony-stimulator factor (GM-CSF) have shown potent antitumor activities through activating innate and adaptive immunities, and reprogramming tumor-promoting myeloid cells from immune-suppressive to immune-active phenotypes. In this study, we showed the effect of radiation, which increased release of tumor antigens so that augment the efficacy of immunotherapy, in combination with IL-12/GM-CSF (RT/12GM) or anti-PDL1 antibody (RT/PDL1) on TAN in advanced 14-day-CT26 colorectoral cancer. We found that both combination treatment significantly suppressed tumor growth, only RT/12GM but not RT/PDL1 can cure mice; radiation or immunotherapy alone single therapies were much less effective. Mechanistic analysis showed that RT/12GM, but not RT/PDL1, greatly increased accumulation of TAN. These TANs were not only impaired in their suppressive activities, but also able to induce T cell proliferation, in accordance with their increased expressions of MHC class I and II, CD40 and CD86, indicating they presented in a status with higher Ag presentation ability. Antibody depletion experiments showed that TAN was required for tumor regression in RT/12GM therapy. Together, our data demonstrate that combination of radiotherapy and IL-12/GM-CSF improved antitumor immunity through enhancing Ag presentation activity and reducing immunosuppressive functions of TAN.

Hydrodesulfurization (HDS) is an important technology to produce clean fuels, in which the nickel phosphide catalysts exhibit excellent catalytic performances. In this work, a series of NixP/SBA-15 catalysts with various P/Ni molar ratios were prepared using the mesoporous molecular sieve SBA-15 as the support. The structure and surface properties of the catalysts were characterized by X-ray diffraction (XRD), N2 sorption analysis, transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FTIR), and in situ diffuse reflectance infrared Fourier transfer spectroscopy (DRIFTS). The catalytic performances for the HDS of dibenzothiophene (DBT) were evaluated. The results demonstrated that the NixP/SBA-15 catalysts possessed high specific surface area and the mesoporous structures, which benefited the elimination of the internal diffusion limitation in the HDS reactions. Both Ni2P and Ni12P5 phases showed catalytic activity in HDS reactions while Ni2P was more active. The optimal P/Ni molar ratio was about 0.75. The DBT conversion can reach 95.8% under the reaction condition of pressure at 3.0 MPa, H2:oil=600, WHSV at 26.7 h-1, and temperature at 340oC. In situ DRIFTS spectra indicated that the coordinative unsaturated Nid+ (0

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide with few therapeutic options. Radiation is wildly used for cancer treatment, but local relapse often occurs. Interleukin 12 (IL-12) has potent antitumor activities by activating natural killer cells (NK) and CD8+ T cells, reprogramming myeloid cells to an immune active phenotype, and inhibiting new blood vessel formation. We hypothesized that combined radiation and IL-12 treatment may change tumor suppressive microenvironment and induce antitumor immune responses. Our data showed that only combination of radiation and intratumoral injection of adenovirus encoding IL-12 (Ad/IL-12) led to tumor regression in mice with large subcutaneous or orthotopic HCC, and significantly prolonged their survival. Mechanistic studies revealed that combination therapy enhanced antigen (Ag) presentation ability of DCs by increasing MHC class II, CD40 and CD86 expression. Combination therapy also significantly reduced numbers of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and impaired their suppressive functions by reducing reactive oxygen species (ROS) production. Accordingly, combination therapy significantly increased the cell numbers of tumor-infiltrating CD8+ T cells and their expressions of CD107a and TNF-α. The cell numbers of tumor-infiltrating NK cells was not affected, but the expression of activation markers was significantly increased after treatment. Together, our results demonstrate that combination therapy effectively against advanced HCC through activating tumor-infiltrating NK cells and tumor-specific CD8+ T cells, enhancing Ag presentation ability of DCs while reducing the suppressive functions of MDSCs.

The yttrium metal-organic framework (Y-MOF) was synthesized with the rare earth metal yttrium as the metal ions and 1 ,3 ,5-trimesic acid (BTC ) as organic ligand under hydrothermal conditions . The absorption desulfurization properties and the absorption desulfurization kinetics of Y-MOF in the thiophene/n-octane model oil were investigated . The adsorption desulfurization kinetics equation and the adsorption desulfurization isotherm of Y-M OF were obtained .The results showed that the Y-MOF had excellent adsorption desulfurization ability under the optimum desulfurization conditions of mmodel oil/madsorbent = 100 and 303 K .The adsorption desulfurization rate and adsorption capacity of Y-MOF for sulfur reached 80.7% and 30.7 mgS/g , respectively .The adsorption process of thiophene on Y-MOF followed the quasi two level dynamic model of dqt/dt= 0.007 (31.97-qt)2 .When the liquid space velocity was from 1.0 h-1 to 1.8 h-1 , the capacity of Y-MOF for adsorption removal thiophene was from 2.21% to 1.80% .

A series of Mo-Ni2P/SBA-15 catalysts with various Mo loadings were prepared by impregnating nickel nitrate, diamnnoniunn hydrogen phosphate, and ammonium molybdate onto an SBA-15 support, followed by temperature-programmed reduction (TPR) under H-2. The structure of the catalysts was characterized by Xray diffraction (XRD),N-2 adsorption-desorption, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The catalytic performance was evaluated in the hydrodesulfurization (HDS) of dibenzothiophene (DBT). The results indicate that the mesoporous structure was maintained and the Ni2P phase was present in all of the catalysts. The chemical states of Ni were Ni delta+ and Ni2+, the chemical states of P were P delta- and P5+, and the chemical states of Mo were Mo delta+ and Mo6+. Mo was shown to promote the HDS catalytic performance of Ni2P/SBA-15 catalysts. The Mo-Ni2P/SBA-15 catalysts with 1% (w, mass fraction) Mo loading exhibited the highest HDS activity. The conversion of the DBT reached 99.03% under reaction conditions of 380 degrees C and 3.0 MPa. The HDS of DBT proceeded mainly via the direct desulfurization (DDS) pathway over all of the tested Mo-Ni2P/SBA-15 catalysts.

A series of Co-Ni2P/SBA-15 catalysts with various Co contents, Ni2P contents and P/Ni molar ratios were prepared by impregnating nickel nitrate, diammonium hydrogen phosphate, and then cobalt nitrate into SBA-15 support followed by temperature-programmed reduction in a H2 flow. The catalyst structure was characterized by X-ray diffraction (XRD), high resolution-transmission electron microscopy (HR-TEM) and N2 adsorption-desorption techniques and their catalytic performance of the hydrodesulfurization (HDS) of dibenzothiophene (DBT) was evaluated. The effects of Co contents, Ni2P contents and P/Ni molar ratios on the catalyst structure and HDS of DBT over the Co-Ni2P/SBA-15 catalyst were investigated. The results indicated that the mesoporous structure was mainly maintained and the nickel phosphides were well dispersed in all of the characterized catalysts. The 4Co-25Ni2P/SBA-15 (P/Ni = 0.8) catalyst with the Co and Ni2P contents of 4 wt% and 25 wt%, respectively, and the P/Ni molar ratio of 0.8 showed the highest catalytic performance for HDS of DBT. Under the reaction conditions of 380°C and 3.0 MPa, the DBT conversion can reach 99.62%. The HDS of DBT proceeded mainly via the direct desulfurization (DDS) pathway with biphenyl (BP) as the dominant product on all of the catalysts and the BP selectivity was slightly enhanced after the introduction of Co promoters.