Titers and capacity of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: a single-blinded, randomized clinical trial

BackgroundBooster vaccination is important because of waning immunity and variant immune evasion. We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. Methods and findingsHCW at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2, half-dose mRNA-1273, mRNA-1273, and MVC-COV1901. The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. 340 HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. Anti-spike IgG increased by a fold of 8.4 for MCV-COV1901, 32.2 for BNT162b2, 47.6 for half-dose mRNA-1273 and 63.2 for mRNA1273. The live virus microneutralization assay (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron variant were 6.4 to 13.5 times lower than those against the wild type. Serum neutralizing antibody against omicron variant was undetectable in 60% of the participants who received MCV-COV1901 as a booster by LVMNA. By using pseudovirus neutralizing assay, we found that neutralization activity in the four groups against omicron variant were 4.6 to 5.2 times lower than that against the D614G. All booster vaccines induced comparable T cell response. ConclusionsThird dose booster not only increases neutralizing antibody titer but also enhances antibody capacity against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those after primary series of ChAdOx1 nCov-19. Trial registrationClinicalTrials.gov NCT05132855

Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

Sequence variation among SARS-CoV-2 isolates in Taiwan

Taiwan experienced two waves of imported cases of coronavirus disease 2019 (COVID-19), first from China in January to late February, followed by those from other countries starting in early March. Additionally, several cases could not be traced to any imported cases and were suspected as sporadic local transmission. Twelve full viral genomes were determined in this study by Illumina sequencing either from virus isolates or directly from specimens, among which 5 originated from clustered infections. Phylogenetic tree analysis revealed that these sequences were in different clades, indicating that no major strain has been circulating in Taiwan. A deletion in open reading frame 8 was found in one isolate. Only a 4-nucleotide difference was observed among the 5 genomes from clustered infections.

Quantitative analysis of proteins related to chemoresistance to paclitaxel and carboplatin in human SiHa cervical cancer cells via iTRAQ / 부인종양

Objective@#This study aimed to identify proteins related to paclitaxel and carboplatin chemoresistance in cervical cancer. @*Methods@#Quantitative proteomic analysis was performed on normal SiHa cells and those treated with paclitaxel and carboplatin for 14 days, with isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify related processes and differentially expressed proteins. @*Results@#A total of 67 and 96 differentially expressed proteins were identified in the paclitaxel- and carboplatin- treated groups, respectively. GO and KEGG enrichment analyses identified 53 (43 upregulated and 10 downregulated) and 85 differentially expressed proteins (70 upregulated and 15 downregulated) in the paclitaxel- and carboplatin-treated groups, respectively. The cell counting kit-8 results revealed that APOA1 was overexpressed in both the paclitaxel- and carboplatin- resistant SiHa cells compared with the control cells. Immunohistochemistry showed that APOA1 was highly expressed in the paclitaxel- and carboplatin- resistant squamous cell carcinoma of the cervix. @*Conclusion@#This study is the first to use iTRAQ to identify paclitaxel- and carboplatin- resistance proteins in cervical cells. We identified several proteins previously unassociated with paclitaxel and carboplatin resistance in cervical cancer, thereby expanding our understanding of paclitaxel and carboplatin resistance mechanisms. Moreover, these findings indicate that the APOA1 protein could serve as a potential marker for monitoring and predicting paclitaxel and carboplatin resistance levels.

Effect of tamoxifen on endometrium of patients after breast cancer operation / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the clinicopathological effects of taking tamoxifen(TAM)on endometrium after breast cancer operation.METHODS: From January 2011 to December 2017,622 cases of breast cancer were treated in Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Among them,197 patients took TAM,and 59 patients who took TAM underwent hysteroscopic surgery due to abnormal vaginal bleeding or ultrasound endometrial abnormalities.The 59 patients were divided into premenopausal and postmenopausal groups to analyze the pathological condition;the medication time was defined as 3 years and 5 years,so as to observe the endometrial pathology.Set the endometrial abnormal hyperplasia includes: endometrial cancer and the endometrial atypical hyperplasia, and the rest are benign endometrial lesions and the normal endometrium, and then analyze the ultrasound criteria for abnormal endometrial thickening in premenopausal and postmenopausal according to the endometrial pathology.RESULTS: Among the 197 patients who took TAM after breast cancer,59 patients underwent hysteroscopic surgery,32.2%(19/59)of them visited the hospital because of abnormal vaginal bleeding,76.3%(45/59)were pathologically confirmed to have a lesion,in which the endometrial polyps was with the highest incidence.The incidence of endometrial cancer after menopause was 20.0%(6/30),premenopausal endometrial cancer 3.4%(1/29),and atypical hyperplasia before menopause was 20.7%(6/29).When taking TAM for more than 3 or 5 years,the incidence of endometrial cancer and atypical hyperplasia increased.Premenopausal ultrasound endometrial thickness is associated with abnormal endometrial hyperplasia(P=0.035).The endometrial thickness 15 mm can be used as the best diagnostic ultrasound cut-off for the diagnosis of premenopausal abnormal endometrial thickening. Postmenopausal ultrasound endometrial thickness was not associated with abnormal endometrial hyperplasia(P=0.631).CONCLUSION: Taking TAM after breast cancer surgery can result in endometrial polyps and endometrial hyperplasia.Premenopausal patients can also have endometrial cancer and atypical hyperplasia,so the endometrial monitoring should not be ignored.Those who take TAM for more than 3 years need to be more alert to the occurrence of endometrial lesions.The premenopausal B-ultrasound endometrial thickness 15 mm can be used as the best diagnostic ultrasound cut-off for the diagnosis of abnormal endometrial thickening. After the menopause, the endometrial thickness of 5 mm was still used as the standard for abnormal endometrial thickening.