ABSTRACT
Chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine efficacy in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory recall responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased TEMRA cell numbers, as has been previously reported; however, this did not impact Spike-specific CD4+ T cell memory recall responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults. Key PointsCMV seropositive older adults have more EMRA and terminally differentiated T cells CMV seropositivity does not prevent antibody maintenance after SARS-CoV-2 vaccination CMV seropositivity does not impede SARS-CoV-2 vaccine T cell memory recall responses
ABSTRACT
A comparison of SARS-CoV-2 wild-type and the beta variant virus neutralization capacity between 2 and 3 mRNA vaccine series in nursing home residents, and between nursing home and assisted living residents strongly supports 3rd dose vaccine recommendations, and equivalent polices for nursing homes and assisted living settings. Findings suggest that residents mount a robust humoral response to a 3rd mRNA vaccination, and have greater neuralization capacity compared to a 2 dose series.
ABSTRACT
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.
ABSTRACT
Background and Objectives@#Systemic scleroderma (SSc) is a rare and serious connective tissue disease, an autoimmune disease, and a rare refractory disease. In this study, preventive effect of single systemic human umbilical cord mesenchymal stem cells (UC-MSCs) transfusion on SSc was preliminarily explored. @*Methods@#and Results: SSc mouse model was established by daily intradermal injection of Hypochlorite (HOCl). SSc mice were treated by single transfusion of UC-MSCs at 0.625×10 5 , 2.5×105 and 1×106 respectively. At the 42nd day of intradermal injection of HOCl, the symptoms showed up by skin and alveolar wall thickening, lymphocytic infiltration, increased collagen in skin/lung, and the increased proportion of CD3 ＋ CD4＋ CD25＋ FoxP3＋ cells (a Treg subset) in spleen. After UC-MSCs transfusion, the degree of skin thickening, alveolar wall thickening and lymphocyte infiltration were decreased, the collagen sedimentation in skin/lung was decreased, and the proportion of CD3＋ CD4＋ CD25＋FoxP3＋ cells was decreased. @*Conclusions@#UC-MSC can achieve a preventive effect in SSc mice by fibrosis attenuation and immunoregulation.
ABSTRACT
Background and Objectives@#Systemic scleroderma (SSc) is a rare and serious connective tissue disease, an autoimmune disease, and a rare refractory disease. In this study, preventive effect of single systemic human umbilical cord mesenchymal stem cells (UC-MSCs) transfusion on SSc was preliminarily explored. @*Methods@#and Results: SSc mouse model was established by daily intradermal injection of Hypochlorite (HOCl). SSc mice were treated by single transfusion of UC-MSCs at 0.625×10 5 , 2.5×105 and 1×106 respectively. At the 42nd day of intradermal injection of HOCl, the symptoms showed up by skin and alveolar wall thickening, lymphocytic infiltration, increased collagen in skin/lung, and the increased proportion of CD3 ＋ CD4＋ CD25＋ FoxP3＋ cells (a Treg subset) in spleen. After UC-MSCs transfusion, the degree of skin thickening, alveolar wall thickening and lymphocyte infiltration were decreased, the collagen sedimentation in skin/lung was decreased, and the proportion of CD3＋ CD4＋ CD25＋FoxP3＋ cells was decreased. @*Conclusions@#UC-MSC can achieve a preventive effect in SSc mice by fibrosis attenuation and immunoregulation.
ABSTRACT
Coronavirus Disease 2019 (COVID-19) is a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While detection of SARS-CoV-2 by polymerase chain reaction with reverse transcription (RT-PCR) is currently used to diagnose acute COVID-19 infection, serological assays are needed to study the humoral immune response to SARS-CoV-2. SARS-CoV-2 IgG/A/M antibodies against SARS-CoV-2 spike (S) protein and its receptor-binding domain (RBD) were characterized using an enzyme-linked immunosorbent assay (ELISA) and assessed for their ability to neutralize live SARS-CoV-2 virus in recovered subjects who were RT-PCR-positive (n=153), RT-PCR-negative (n=55), and control samples collected pre-COVID-19 (n=520). Anti-SARS-CoV-2 antibodies were detected in 90.9% of resolved subjects up to 180 days post-symptom onset. Anti-S protein and anti-RBD IgG titers correlated (r= 0.5157 and r = 0.6010, respectively) with viral neutralization. Of the RT-PCR-positive subjects, 22 (14.3%) did not have anti-SARS-CoV-2 antibodies; and of those, 17 had RT-PCR cycle threshold (Ct) values >27, raising the possibility that these indeterminate results are from individuals who were not infected, or had mild infection that failed to elicit an antibody response. This study highlights the importance of serological surveys to determine population-level immunity based on infection numbers as determined by RT-PCR.
ABSTRACT
Immunohistochemistry was used to detect the protein expression of Snail in 5 specimens jusxta-eancerous normal breast tissues, 35 specimens of cancerous tissues without metastasis and 20 specimens of breast carcinoma with lymphonode metastasis. Breast carcinoma cell line MDA-MB-231 was transfected with antisense Snail. Results showed that the expression of Snail protein was significantly higher in breast carcinomas than in their normal tissues. The mRNA and protein expressions of Snail in the breast carcinoma cells treated with antisense Snail was significantly decreased while the E-cadherin protein significantly increased (both P < 0.05). The number of invasive ceils treated with antisense Snail was (10.5±1.3)%, while in treated with EGFP was (68.2±2.1)% (P < 0.05). The abnormal expression of Snail contribute to the invasiveness of breast carcinoma. The antisense Snail could prevent the cells ability to invade in vitro, and the effect is related with the up-regulated E-cadherin protein.
ABSTRACT
The role of serum and glucocorticoid-induced kinase 1 (SGK1) pathway in the connective tissue growth factor (CTGF) expression was investigated in cultured human mesangial cells (HMCs) under high glucose. By using RT-PCR and Western blot, the effect of SGK1 on the CTGF expression in HMCs under high glucose was examined. Overexpression of active SGK1 in HMCs transfected with pIRES2-EGFP-S422D hSGK1 (SD) could increase the expression of phosphorylated SGK1 and CTGF as compared with HMCs groups transfected with pIRES2-EGFP (FP) under high glucose or normal glucose. Overexpression of inactive SGK1 in HMCs transfected with pIRES2-EGFP-K127N hSGK1 (KN) could decrease phosphorylated SGK1 and CTGF expression as compared with HMCs groups transfected with FP under high glucose. In conclusion, these results suggest that high glucose-induced CTGF expression is mediated through the active SGK1 in HMCs.
Subject(s)
Cells, Cultured , Connective Tissue Growth Factor/genetics , Connective Tissue Growth Factor/metabolism , Glucose/pharmacology , Immediate-Early Proteins/metabolism , Immediate-Early Proteins/physiology , Mesangial Cells/cytology , Mesangial Cells/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/physiology , Signal Transduction/drug effectsABSTRACT
The relationship of connexin43 (Cx43) and bystander effect in ovarian tumor cells in herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy in vitro was explored and the effect of all-trans retinoic acid (RA) on the expression of Cx43 and bystander effect investigated. The Cx43 expression was detected by flowcytometry, Western blot, and immunofluorescence in two ovarian tumor cell lines OVCAR3, CaOV3 before and after RA treatment. Bystander effect was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium. Following exposure to ganciclovir, there was much greater bystander killing in OVCAR3 than that in CaOV3 (P<0.05). The expression of Cx43 was detected in OVCAR3 by flowcytometry and Western blot, but it could not be detected in CaOV3. The expression of Cx43 in both cell lines could be induced by RA. Immunofluoresence staining showed that Cx43 protein of OVCAR3 was located on membrane surface, whereas CaOV3 in cytoplasm. RA could not change the location of Cx43 protein in both cell lines. There is relationship between Cx43 expression and HSV-TK/GCV bystander effect. HSV-TK/GCV bystander effect can be enhanced by RA in ovarian cancer.
