High neutralizing antibody levels against SARS-CoV-2 Omicron after UB-612 booster vaccination

The highly transmissible Omicron variant has caused high rates of breakthrough infections among vaccinated and convalescent individuals. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increases neutralizing antibody levels by 131-, 61- and 49-fold against ancestral SARS-CoV-2, Omicron BA.1 and BA.2 variants, respectively. Based on the RBD protein binding antibody responses, we estimated a [~]95% efficacy against symptomatic COVID-19 caused by the ancestral strain after a UB-612 booster. Our results support UB-612 vaccine as a potent booster against current and emerging SARS-CoV-2 variants.

A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model

A novel multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease is described in this report. The initial development and characterization experiments are presented along with proof-of-concept studies for the vaccine candidate UB-612. UB-612 consists of eight components rationally designed for induction of potently neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist at low concentration as an excipient, and aluminum phosphate adjuvant. Through immunogenicity studies in Guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provides excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses. In challenge studies, UB- 612 vaccination reduced viral load and prevented development of disease in mouse and non-human primate challenge models. With a Phase 1 trial completed, a Phase 2 trial ongoing in Taiwan, and additional trials planned to support global authorizations, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 infection and COVID-19 disease. Author SummarySARS-CoV-2 virus, the causative agent of Coronavirus Disease 2019 (COVID-19), has spread globally since its origin in 2019, causing an unprecedented public health crisis that has resulted in greater than 4.7 million deaths worldwide. Many vaccines are under development to limit disease spread and reduce the number of cases, but additional candidates that promote a robust immune response are needed. Here, we describe a multitope protein-peptide vaccine platform that is unique among COVID-19 vaccines. The advantages of our approach are induction of both high levels of neutralizing antibodies as well as a Th/CTL response in the vaccinated host, which mimics the immune response that occurs after natural infection with SARS-CoV-2. We demonstrate that our vaccine is immunogenic and effective in preventing disease in several animal models, including AAV- hACE-2 transduced mice, and both rhesus and cynomolgus macaques. Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. Our study provides an additional, novel vaccine candidate for advancement in clinical trials to treat and prevent SARS-CoV-2 infection and COVID-19 disease.

Treatment and prognosis of pT1N0M0 Luminal B-like breast cancer / 肿瘤

Objective: To analyze the clinicopathological characteristics, treatment and prognosis of Luminal B-like breast cancer in pT1N0M0 stage. Methods: The data of 300 patients with stage pT1N0M0 Luminal B-like breast cancer who underwent surgery in Tianjin Medical University Cancer Institute and Hospital from January 2010 to January 2013 were collected. The clinicopathological characteristics, treatment and prognosis were retrospectively analyzed by using the statistical methods such as χ2 test, univariate analysis, COX multivariate analysis, Kaplan-Meier and so on. Results: In 300 cases of breast cancer, there were 24 cases (8%) in pT1aN0M0 stage, 115 cases (38.3%) in pT1bN0M0 stage, and 161 cases (53.7%) in pT1cN0M0 stage. Intergroup analysis (χ2 test) showed that only histological grade was related to tumor size (P = 0.004). Univariate analysis showed that age, histological grade, human epidermal growth factor receptor-2 (HER-2) expression, Ki-67 expression and chemotherapy had an effect on the five-year disease-free survival (DFS) of patients (all P 0.05). For the patients in pT1cN0M0, the five-year DFS rate in taxane combined with anthracycline chemotherapy group was significantly higher than that in taxane/anthracycline alone chemotherapy group (P = 0.042), but the five-year OS rate was not significant different between the two groups (P = 0.711). Conclusion: Postoperative adjuvant chemotherapy can improve the prognosis of patients with stage pT1N0M0 Luminal B-like breast cancer. The patients in pT1a-bN0M0 stage may be given taxanes/anthraquinones chemotherapy for reducing overtreatment. For the patients in pT1cN0M0 stage, the prognosis will be better when the taxane combined with anthracycline chemotherapy is given.

Risk factors for cerebral infarction in patients with capsular warning syndrome / 国际脑血管病杂志

Objective To investigate the risk factors for the occurrence of cerebral infarction in patients with capsular warning syndrome (CWS). Methods Consecutive patients with transient ischemic attack (TIA) meeting the CWS clinical manifestations were col ected retrospectively. They were divided into either a cerebral infarction group or a non-cerebral infarction group according to the brain diffusion weighted imaging findings. The independent risk factors for patients with CWS were identified through the comparison of demographic and baseline clinical data. Results A total of 39 patients were enrol ed, including 25 males (64. 1%) and 14 females (35. 9%), and their mean age was 58. 9 ± 10. 3 years. There were 21 patients in the cerebral infarction group and 18 in the non-cerebral infarction group. Compared with the non-cerebral infarction group, the age of patients in the cerebral infarction group was older (62. 5 ± 9. 3 years vs. 54. 8 ± 10. 2 years;t=2. 470, P=0. 018). The constituent ratio of the patients with a history of previous stroke or transient ischemic attack was higher (33. 3% vs. 5. 6%; P=0. 049), the fasting blood glucose level was higher (8. 2 ± 3. 2 mmol/L vs. 6. 0 ± 1. 3 mmol/L; t=2. 748, P=0. 009), and ABCD2 score was higher (5. 2 ± 1. 1 vs. 3. 5 ± 1. 1;t=4. 734, P<0. 001). Multivariate logistic regression analysis showed that the ABCD2 score was an independent risk factor for cerebral infarction in patients with CWS (odds ratio, 4. 529, 95% confidence interval 1. 233-16. 627;P=0. 023). Conclusions The higher ABCD2 score was an independent risk factor for the occurrence of cerebral infarction in patients with CWS. It can be used as an evaluation tool for predicting the risk of cerebral infarction in patients with CWS.