Studies of SARS virus vaccines

1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.published_or_final_versio

Studies of SARS virus vaccines

1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.published_or_final_versio

Sun exposure to the eyes: predicted UV protection effectiveness of various sunglasses.

The aim of this study was to assess solar ultraviolet radiation (UVR) doses received by the eyes in different exposure situations, and to predict the sun protection effectiveness provided by various styles of sunglasses at facial, periorbital, and ocular skin zones including the cornea and accounting for different head positions. A 3D numeric model was optimized to predict direct, diffuse and reflected erythemally weighted UVR doses received at various skin zones. Precisely defined facial, periorbital, and ocular skin zones, sunglasses (goggles, medium-, and large-sized sunglasses) and three head positions were modeled to simulate daily (08:00-17:00) and midday (12:00-14:00) UVR doses. The shading from sunglasses' frame and lenses' UVR transmission were used to calculate a predictive protection factor (PPF [%]). Highest ocular daily UVR doses were estimated at the uncovered cornea (1718.4 J/m <sup>2</sup> ). Least sun protection was provided by middle-sized sunglasses with highest midday dose at the white lateral (290.8 J/m <sup>2</sup> ) and lateral periorbital zones (390.9 J/m <sup>2</sup> ). Goggles reached almost 100% protection at all skin zones. Large-sized sunglasses were highly effective in winter; however, their effectiveness depended on diffuse UVR doses received. In "looking-up" head positions highest midday UVR doses were received at the unprotected cornea (908.1 J/m <sup>2</sup> ), totally protected when large-sized sunglasses are used. All tested sunglass lenses fully blocked UVR. Sunglasses' protection effectiveness is strongly influenced by geometry, wearing position, head positions, and exposure conditions. Sunglasses do not totally block UVR and should be combined with additional protection means. 3D modeling allows estimating UVR exposure of highly sensitive small skin zones, chronically exposed and rarely assessed

Calcium channel α2δ1 subunit (CACNA2D1) enhances radioresistance in cancer stem-like cells in non-small cell lung cancer cell lines

Xin Sui,1,* Jian-Hao Geng,1,* Yong-Heng Li,1 Guang-Ying Zhu,2 Wei-Hu Wang1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, China; 2Department of Radiation Oncology, National Clinical Research Center for Respiratory Disease, Center for Respiratory Disease, Lung Cancer Center, China-Japan Friendship Hospital, Peking University Health Science Center, Beijing, China *These authors contributed equally to this work Purpose: Radiotherapy is a major treatment method for patients with non-small cell lung cancer (NSCLC). However, the presence of radioresistant cancer stem cells (CSCs) may be associated with disease relapse or a poor outcome after radiotherapy. Voltage-gated calcium channel α2δ1 subunit (encoded by the gene CACNA2D1) isoform 5 is a marker of CSCs in hepatocellular carcinoma. This study aimed to investigate the radiosensitivity of α2δ1-high cells in NSCLC cell lines. Materials and methods: NSCLC cell lines A549, H1975, H1299, and PC9 were used. CACNA2D1-knockdown and CACNA2D1-overexpressing cell lines were established by lentiviral infection. Colony formation assay was performed to determine radiosensitivity. Sphere formation assay in serum-free medium was performed to evaluate self-renewal capacity. Proteins associated with DNA damage repair were analyzed by immunofluorescence or Western blot. The monoclonal antibody of α2δ1 was applied alone or in combination with radiation either in vitro or in vivo to determine the anti-tumor effect of the antibody. Results: α2δ1-high cells showed greater sphere-forming efficiency than α2δ1-low cells and were relatively resistant to radiation. CACNA2D1 knockdown in A549 cells enhanced radiosensitivity, whereas CACNA2D1 overexpression in PC9 and H1975 cells reduced radiosensitivity, suggesting that α2δ1 imparted radioresistance to NSCLC cells. Analysis of proteins involved in DNA damage repair suggested that α2δ1 enhanced the efficiency of DNA damage repair. The monoclonal antibody of α2δ1 had a synergistic effect with that of radiation to block the self-renewal of α2δ1-high cells and enhanced the radiosensitivity of α2δ1-positive cells in colony formation assays. The combination of the α2δ1 antibody with radiation repressed A549 xenograft growth in vivo. Conclusion: α2δ1 enhances radioresistance in cancer stem-like cells in NSCLC. The α2δ1 monoclonal antibody sensitizes α2δ1-high cells to radiation, suggesting that the antibody may be used to improve the treatment outcome when combined with radiation in NSCLC. Keywords: radioresistance, cancer stem cell, calcium channel, DNA damage repai