Human alphaherpesvirus 2 (HSV-2) is the main pathogen resulting human genital herpes, which poses a major threat to the socio-economic development, while there is no effective vaccine. In this study, we developed a novel lipopolyplex (LPP)-delivered mRNA vaccine expressing the HSV-2 envelope glycoprotein gD and evaluated its immunogenicity in mice. The mRNA vaccine was prepared from the genetically modified gD mRNA synthesized in vitro combined with the LPP delivery platform and it was named gD-ORI mRNA. The expression of gD antigen in the mRNA vaccine was validated in vitro by Western blotting and indirect immunofluorescence assay, then the immune responses induced by this mRNA vaccine in mice were evaluated. The immunization with gD mRNA alone induced strong humoral and cellular immune responses in mice. Robust and long-lasting gD-specific IgG antibodies were detected in the mouse serum after booster immunization with gD-ORI mRNA. The immunized mice exhibited a Th1/Th2 balanced IgG response and robust neutralizing antibodies against HSV-2, and a clear dose-response relationship was observed. The gD-specific IgG antibodies were maintained in mice for a long time, up to 18 weeks post-booster immunization. At the same time, multifunctional gD-specific CD4⁺ and CD8⁺ T cells in vaccinated mice were detected by intracellular cytokine staining (ICS). This novel gD-expressing mRNA vaccine delivered by LPP induces strong and long-lasting immune responses in mice post booster immunization and has a promising prospect for development and application. This study provides scientific evidence and reference for the development of a new mRNA vaccine for HSV-2.
Animals ; Herpesvirus 2, Human/genetics* ; Viral Envelope Proteins/genetics* ; Mice ; Herpes Genitalis/immunology* ; RNA, Messenger/immunology* ; Female ; Mice, Inbred BALB C ; Antibodies, Viral/blood* ; mRNA Vaccines/immunology* ; Antibodies, Neutralizing/blood* ; Humans

Objective:To investigate the level of serum vascular endothelial growth factor (VEGF) and its correlation with clinical symptoms in patients with first-episode drug-naive schizophrenia patients of different genders.Methods:From January 2016 to October 2019, a total of 81 first-episode drug-naive schizophrenia patients(patient group, 41 male, 40 female) and 64 healthy controls (control group, 40 male, 24 female) were included in this study.The serum level of VEGF was detected with flow cytometric bear array (CBA). Positive and negative symptom scale (PANSS) was used to evaluate the relevant clinical symptoms of patients.SPSS 22.0 software was used for statistical analysis.Independent sample t-test and nonparametric test were used for comparison between groups.The relationship between VEGF and clinical variables was analyzed by Pearson correlation analysis and Spearman correlation analysis. Results:The level of serum VEGF in the patient group was significantly lower than that in the control group(148.08(75.89, 208.61)pg/mL, 179.94(99.14, 318.41)pg/mL, Z=-2.20, P=0.028). The total PANSS score((82.71±17.30), (73.45±16.36), t=2.473, P=0.016)and cognitive score((7.88±3.36), (6.23±2.81), t=2.402, P=0.019) in male patients were higher than those in female patients.There was a negative correlation between VEGF level and PANSS negative symptom score in the patient group( r=-0.228, P=0.041), as well as significant negtive correlation between VEGF level and cognitive score in male patients( r=-0.425, P=0.007). Conclusion:The level of serum VEGF is reduced in first-episode patients with schizophrenia, which influences their negative symptom. Moreover, the decline in serum VEGF level is implicated in cognitive impairments in male patients with first-episode schizophrenia.

Objective To investigate the clinical features and antimicrobial susceptibility of neonatal Listeria septicemia.Methods Eleven cases of neonatal Listeria septicemia that were treated in the Huzhou Maternity and Children Health Hospital from March 2013 to March 2017 were enrolled in this study.Clinical data including the results of bacterial culture,antimicrobial susceptibility test and antibiotic treatment were collected and retrospectively analyzed.Moreover,maternal history of Listeria monocytogenes (LM) infection before delivery was retrieved.Results All of the 11 mothers had fever before delivery and nine of them showed different grades of amniotic fluid contamination during delivery.Clinical symptoms of the 11 neonates included dyspnea (11 cases),fever (ten cases),apnea (nine cases),slow response and feeding difficulty (nine cases),convulsion (six cases),vomiting and abdominal distension (two cases),pulmonary hemorrhage (one case),progressive jaundice (one case) and systemic skin bleeding point (one case).All cases showed abnormal results of blood routine test and increased calcitonin and C-reactive protein.Ten cases received cercbrospinal fluid examination,seven of which were abnormal.Altogether 17 strains of LM were isolated from various specimens.These strains were all sensitive to piperacillin-tazobactam,ampicillin-sulbactam,meropenem,vancomycin,cotrimoxazole,ciprofloxacin and gentamycin,but resistant to oxacillin.Strains those were sensitive to penicillin,ampicillin,erythromycin and clindamycin accounted for 10/17,11/17,9/17 and 8/17,respectively.The 11 neonates were treated with piperacillin-tazobactam,meropenem or vancomycin.All of them improved (11/11)and ten were cured (10/11).All cases were followed up through phone calls at one week and one month after discharge.Two were lost to follow-up,while thc others were all in good condition.Conclusions Neonatal Listeria septicemia is usually a severe disease characterized by rapid progression and mainly presented with dyspnea and fever,besides there is a high possibility of purulent meningitis.Some LM strains are resistant to single-agent penicillin antibiotics.However,antibiotics such as piperacillin-tazobactam,meropenem and vancomycin are effective in the treatment of neonatal Listeria septicemia.

Objective To study the meaning of Homocysteine,serum high sensitive C-reactive protein,lipoprotein A and D-two dimer combined detection in the course of coronary heart disease.Methods Select 180 cases suffering from different types of coronary heart disease as group of coronary heart disease,200 healthy people who were in our hospital physical examination qualified over the same period as the control group,all the cases of fasting venous blood was sampled respectively to detect the content of Hcy,hs-CRP,LP(a) and DD.Results Coronary heart disease group of patients with Hcy,hs-CRP,LP(a) and DD levels were significantly higher than those of the control group of healthy persons(t =13.87,10.24,9.86,18.02,P ＜ 0.05),Comparison among different indicators of the patiens with Coronary heart disease:the group of AMI was higher than the group of UAP (t =15.79,9.73,11.47,17.34,all P ＜ 0.05),the group of UAP was higher than the group of SAP (t =16.82,8.14,10.65,18.27,P ＜0.05),the group of SAP was higher than the group of SMI (t =14.36,10.35,9.98,16.52,P ＜ 0.05).Conclusion Monitoring of Hcy,hs-CRP,LP(a) and DD for coronary heart disease,contributes to the understand of the development of the course of coronary heart disease and assess the risk of coronary heart disease.