Potent T cell Responses Induced by Single DNA Vaccine Boosted with Recombinant Vaccinia Vaccine

Plasmid DNA, an effective vaccine vector, can induce both cellular and humoral immune responses. However, plasmid DNA raises issues concerning potential genomic integration after injection. This issue should be considered in preclinical studies. Tiantan vaccinia virus (TV) has been most widely utilized in eradicating smallpox in China. This virus has also been considered as a successful vaccine vector against a few infectious diseases. Potent T cell responses through T-cell receptor (TCR) could be induced by three injections of the DNA prime vaccine followed by a single injection of recombinant vaccinia vaccine. To develop a safer immunization strategy, a single DNA prime followed by a single recombinant Tiantan vaccinia (rTV) AIDS vaccine was used to immunize mice. Our data demonstrated that one DNA prime/rTV boost regimen induced mature TCR activation with high functional avidity, preferential T cell Vβ receptor usage and high sensitivity to anti-CD3 antibody stimulation. No differences in T cell responses were observed among one, two or three DNA prime/rTV boost regimens. This study shows that one DNA prime/rTV boost regimen is sufficient to induce potent T cell responses against HIV.

HIV-Specific IL-2^+ and/or IFN-γ^+ CD8^+ T Cell Reponses during Chronic HIV-1 Infection in Former Blood Donors

Objective Conflicting data have been generated from previous studies to determine which kind of relationship exists between HIV-1 specific CD8 Tcell responses and HIV-1 viral load or CD4 count over the course of infection.In this study,153 HIV-1 infected LTNPs were enrolled to investigate the role of HIV-1 specific CD8 T-cell responses in chronic HIV-1 infection among HIV-1 infected former blood donors.Methods The patients were stratified into three groups according to CD4 count：CD4≥500 cells/μL;350 cells/μL≤CD4〈500 cells/μL;CD4〈350 cells/μL.PBMCs were isolated from the patients＇ anticoagulated blood samples.IL-2 and IFN-γ secretions of CD 8 T cells against 17 HIV-1 consensus B full peptide pools were analyzed by using ICS assay.Results An overall inverse correlation were observed between CD4 count and plasma viral load.Although no significant difference was observed during the comparisons of frequency/breadth of HIV-1 specific CD8 T cell responses,CD4 count stratification analysis showed that different correlation pattern existed in three strata：as for patients whose CD4 counts were less than 350 cells/μL,no significant correlations were identified between frequency/breadth of HIV-1 specific CD8 T cell responses and CD4 count/viral load;as for patients whose CD4 counts ranged from 350 cells /μL to 500 cells/μL,significant correlation was only observed between the response breadth of IL-2＋IFN-γ＋ CD8 T cells and CD4 count;however,as for patients whose CD4 counts were more than 500 cells/μL,direct correlations were identified between IL-2＋IFN-γ＋/IL-2＋/IFN-γ＋ CD8 T cells and viral load or CD4 count.Conclusions Universal consistent inverse correlation was only indentified between CD4 count and viral load.The relationship between HIV-1 specific CD8 T cell responses and CD4 count/viral load varied in different CD4 strata,which showed that better preserved CD4 T cells were correlated with better CD8 T cell functions.

Nasopharyngeal Local Transcriptional Profile upon SARS-CoV-2 Omicron BA.2.2 Breakthrough Infection

The Omicron variants have continued to cause severe acute respiratory syndrome coronavirus 2 infections.To better understand the anti-viral effects of vaccination on host-virus interactions during the outbreak of BA.2.2 Omicron,we conducted RNA-seq transcriptome analysis on nasopharyngeal swabs from COVID-19 patients in Shanghai.This study was performed on selected cases from unvaccinated,fully vaccinated,and booster groups with the same founder virus infection background.We observed predominant immune cell chemotaxis and interleukin-1 production,as well as mucosal keratinization and epidermis development,in unvaccinated patients.In contrast,fully vaccinated subjects exhibited an obvious T-cell activation in the local immune response,whereas B-cell activation was higher in booster-vaccinated cases.In conclusion,our findings suggest that full or booster vaccination provides better adaptive immunity and relieve inflammation at the nasopharyngeal site,thereby reducing the risk of cytokine storm during breakthrough infection.

One-step approach for full-thickness skin defect reconstruction in rats using minced split-thickness skin grafts with Pelnac overlay

Background:Split-thickness skin grafting is the current gold standard for the treatment of traumatic skin loss.However,for patients with extensive burns,split-thickness skin grafting is limited by donor skin availability.Grafting split-thickness skin minced into micrografts increases the expansion ratio but may reduce wound repair quality.Dermal substitutes such as Pelnac can enhance the healing of full-thickness skin wounds,but their application currently requires two surgeries.The present study investigated whether it is possible to repair full-thickness skin defects and improve wound healing quality in a single surgery using Pelnac as an overlay of minced split-thickness skin grafts in a rat model.Methods:A full-thickness skin defect model was established using male Sprague-Dawley rats of 10 weeks old.The animals were randomly divided into control and experimental groups in which Vaseline gauze and Pelnac,respectively,were overlaid on minced split-thickness skin grafts to repair the defects.Wound healing rate and quality were compared between the two groups.For better illustration of the quality of wound healing,some results were compared with those obtained for normal skin of rats.Results:We found that using Pelnac as an overlay for minced split-thickness skin grafts accelerated wound closure and stimulated cell proliferation and tissue angiogenesis.In addition,this approach enhanced collagen synthesis and increased the formation of basement membrane and dermis as well as the expression of growth factors related to wound healing while reducing scar formation.Conclusions:Using minced split-thickness skin grafts overlaid with Pelnac enables the reconstruction of fullthickness skin defects in a single step and can increase the healing rate while improving the quality of wound healing.

Acute-on-Chronic Liver Failure Precipitated by Severe Acute Respiratory Syndrome Coronavirus 2 Infection in a Patient with Hepatitis B Virus-Related Cirrhosis: A Case Report

We present a case of acute-on-chronic liver failure(ACLF)in a patient with hepatitis B virus(HBV)-related decompensated cirrhosis and coronavirus disease 2019(COVID-19).A 58-year-old woman with HBV-related and decompensated cirrhosis without any anti-viral treatment previously was admitted to the hospital due to a confirmed severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.On admission,she was in stable condition.Thoracic computed tomography(CT)and laboratory findings showed no significant abnormalities.Entecavir was initiated promptly for HBV,while antiviral therapy and supportive treatment were initiated for COVID-19.Her lung infection exacerbated after 10days of recurrent fever despite treatments,and there were signs of HBV reactivation.ACLF and multiple organ dysfunction syndrome developed rapidly from day 10 to day 19.The patient’s clinical deterioration was also consistent with pneumonia progression and elevated interleukin 6 levels.SARS-CoV-2 likely precipitated ACLF in cirrhotic patients,either by inducing HBV flare or serving as an acute insult directly.This study discussed the underlying mechanisms of this process and management details.Monitoring HBV status is necessary,and inflammatory parameters might be valuable.HBV suppression should be initiated early,and variceal hemorrhage primary prevention might be beneficial in COVID-19 patients with cirrhosis.

Recent progress in porous Mg-based foam preparation approaches:effect of processing parameters on structure and mechanical property

Porous metals are a class of cellular materials with lightweight and unique mechanical,electrical,thermal,physical and acoustic characteristics.Magnesium and magnesium alloy foams have exhibited excellent advantages.In particular,open-cell Mg-based foams(porous Mg/Mg alloy foams)have been used for bioresorbable implants,CO_(2)trapping systems,filters,heat exchangers,absorbent panels and many other applications.While significant progress has been taken in producing porous Mg-based foams with good structure-property relations,but with a large number of different processing parameters,different mechanical properties and pore morphologies of each porous Mg-based foam,it is essential to understand the individual effects of each aspect of the parameters.Therefore,the present article summarized the effects of available processing parameters on the structure and mechanical properties of the porous Mg-based foams.Finally,the future perspectives to enhance the structure and properties of porous Mg/Mg alloy foams were discussed.

Multifactorial role of HIV-Vpr in cell apoptosis revealed by a naturally truncated 54aa variant

Although antiretroviral therapy(ART)is effective at suppressing the human immunodeficiency virus type 1(HIV-1)replication,HIV-1 infection is still a global public health problem.HIV-1 accessory protein viral protein R(Vpr)is a multifunctional protein with a primary role in regulating cellular apoptosis.[1]The amino acid(aa)positions 52-96 in the C-terminus of Vpr were identified as the apoptosis-regulating domain.[2,3]In this study,we found a natural Vpr variant truncated at the 54 aa position(*54Vpr)from HIV patients in the acquired immune deficiency syndrome(AIDS)phase that mediated both pro-and antiapoptotic cellular effects by interacting with distinct adenine nucleotide translocator(ANT)isoforms.A novel apoptosis-regulating domain was further identified in the 23-37 aa position in the N-terminus of Vpr.

Seeking "protective" and "harmful" immune genes during chronic HIV-1 infection by transcriptome analysis

Human immunodeficiency virus(HIV)-infected individuals exhibit remarkable transcriptomic variation.Transcriptome analyses of antiretroviral therapy(ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies.Here,we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts.The differentially expressed genes were analyzed between long-term non-progressors,viremic non-progressors and typical progressors,and between elite controllers and non-elite controllers among the long-term nonprogressors.Several genes related to T-cell growth,proliferation and differentiation and antiapoptosis were upregulated,whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors.The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up,which included 51 genes significantly associated with slower disease progression,and 210 genes associated with aggressive disease progression.Overall,our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses.Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART,such as the administration of interleukin-7,healthy allogenic CD4^(+)T cells(providing CD4^(+)T-cell growth factors),or Tregs.