Single-dose respiratory mucosal delivery of next-generation viral-vectored COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2

The emerging SARS-CoV-2 variants of concern (VOC) increasingly threaten the effectiveness of current first-generation COVID-19 vaccines that are administered intramuscularly and are designed to only target the spike protein. There is thus a pressing need to develop next-generation vaccine strategies to provide more broad and long-lasting protection. By using adenoviral vectors (Ad) of human and chimpanzee origin, we developed Ad-vectored trivalent COVID-19 vaccines expressing Spike-1, Nucleocapsid and RdRp antigens and evaluated them following single-dose intramuscular or intranasal immunization in murine models. We show that respiratory mucosal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the three-arm immunity, consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells, and mucosal trained innate immunity. We further show that single-dose intranasal immunization provides robust protection against not only the ancestral strain of SARS-CoV-2, but also two emerging VOC, B.1.1.7 and B.1.351. Our findings indicate that single-dose respiratory mucosal delivery of an Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy against current and future VOC. This strategy has great potential to be used not only to boost first-generation vaccine-induced immunity but also to expand the breadth of protective T cell immunity at the respiratory mucosa.

Effect of capecitabine on breast cancer failing in treatment with different receptor expression / 中国医师进修杂志

Objective To observe the effect of capecitabine alone against breast cancer failing in treatment with different receptor expression. Methods Ninety-six cases of breast cancer patients failing in treatment with different receptor expression were collected. They were treated with capecitabine alone, 1 000-1 250 mg/m2, D1-14, 21 d for 1 cycle. All the treatment was repeated 3 cycles at least. According to age, menopausal status, Eastern Cooperative Oncology Group (ECOG) scores, estrogen and progesterone receptor status, human epidermal growth factor receptor-2 expression, number of chemotherapy cycle, the patients were divided into difference groups. χ2 test was used to do single factor analysis and the independent factor affecting the progression free survival time (PFS) was analyzed by Cox regression model. Results The rate of objective effect in 96 breast cancer patients was 51.0%(49/96). PFS was 2-46 months, and median time was 7.0 months. In hematologic toxicity:Ⅰdegree was in 4 cases,Ⅱdegree in 3 cases, andⅢdegree in 5 cases. In digestive tract toxicity:Ⅰdegree was in 5 cases, andⅡdegree in 4 cases. In hand foot syndrome: I degree was in 3 cases, Ⅱ degree was in 1 case, and Ⅲ degree in 1 cases. Cox regression model showed that the number of chemotherapy cycle was the independent factor affecting the PFS (OR = 6.45, 95% CI 3.04- 13.71, P<0.01). Conclusions The treatment of breast cancer with capecitabine alone has good curative effect, and the number of chemotherapy cycles number is the independent influencing factor of RFS.

The therapeutical effect and toxicity of home-made paclitaxel and cisplatin combination in metastatic breast cancer / 中国医师进修杂志

ObjectiveTo evaluate the therapeutical effect and toxicity of home-made paclitaxel and cisplatin combination in metastatic breast cancer.Methods Home-made paclitaxel 175 mg/m2,d1 intravenous drip,cisplatin 80 mg/m2,d1-3 intravenous drip,21-28 d was one cycle,all patients continuous course treatment for 2-6 cycles,then the effect was evaluated.ResultsAll the patients received meso-cycle were 4 (2-6) cycles chemotherapy.The total effective rate was 56.60％ (30/53),disease control rate was 81.13％(43/53 ).The rates of internal organ metastasis and non-internal organ metastasis,before menopause and after menopause had no significant difference [56.76％ (21/37) vs.56.25％ (9/16),59.09％ (13/22) vs.54.84％ ( 17/31 ),P ＞ 0.05 ].The median existence time for all the patients was 18.8 ( 12-27 ) months.The survival rate was 56.60％ (30/53) and 30.19％ (16/53) for 1 and 2 years respectively.The major toxieities were gastrointestinal reaction,alopeoia and myelosuppression,the rates of nerve and heart toxicities were less,15.09％ (8/53) and 7.55％ (4/53) respectively.ConclusionThe therapeutic effect of home-made paclitaxel and cisplatin combination in metastatic breast cancer is good,it is to be worth to spread in clinic.