Immunoinformatics Prediction and Protective Efficacy of Vaccine Candidate PiuA-PlyD4 Against Streptococcus Pneumoniae.

Purpose: This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments. Methods: In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored. Results: PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81±2.32) ×105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process. Conclusion: The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.

Investigating the Correlation Between HLA-II Gene Polymorphism and RhE Alloimmunization in Pregnant Chinese Women.

The Rhesus (Rh) blood group is a significant and complicated biological system in humans. Incompatible transfusion or pregnancy with Rh antigens can lead to the production of alloantibodies, among which the anti-E antibody is prevalent. The relationship between Anti-E antibody and HLA-II gene polymorphism in Chinese pregnant women is worth exploring. Our aim in this study was to verify the correlation between HLA-II gene polymorphisms and RhE alloimmunization in pregnant Chinese women through HLA-II typing and DR-RhE structural prediction. In total, 94 anti-E-negative pregnant women and 103 anti-E-positive pregnant women were enrolled from Southwest China Second Hospital, and HLA-II genotyping was performed using next-generation sequencing. NetMHCpan software was used to predict the binding of E -derived anchoring peptides to HLA-DRB1 molecules. AlphaFold was used to analyze the differences in antigen presentation based on the structure of major histocompatibility complex peptides. The HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 haplotype showed a significant positive association with anti-E. One E-derived anchoring peptide (219FWPSVNSPL227) was predicted to bind to the HLA-DRB1*09:01 molecule. The interaction between the 60Ser of DR9 and 226pro of RhE comprised one hydrogen bond. This study demonstrated that HLA-II haplotypes are associated with allo-anti-E antibodies in pregnant women from Sichuan Province, China. The HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 phenotype may enhance the formation of anti-E alloantibodies, and the HLA-DRB1*09:01 molecule may play a key role in alloimmunity.

Construction and protective efficacy of a novel Streptococcus pneumoniae fusion protein vaccine NanAT1-TufT1-PlyD4.

During the past decades, with the implementation of pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCVs), a dramatic reduction in vaccine type diseases and transmissions has occurred. However, it is necessary to develop a less expensive, serotype-independent pneumococcal vaccine due to the emergence of nonvaccine-type pneumococcal diseases and the limited effect of vaccines on colonization. As next-generation vaccines, conserved proteins, such as neuraminidase A (NanA), elongation factor Tu (Tuf), and pneumolysin (Ply), are promising targets against pneumococcal infections. Here, we designed and constructed a novel fusion protein, NanAT1-TufT1-PlyD4, using the structural and functional domains of full-length NanA, Tuf and Ply proteins with suitable linkers based on bioinformatics analysis and molecular cloning technology. Then, we tested whether the protein protected against focal and lethal pneumococcal infections and examined its potential protective mechanisms. The fusion protein NanAT1-TufT1-PlyD4 consists of 627 amino acids, which exhibits a relatively high level of thermostability, high stability, solubility and a high antigenic index without allergenicity. The purified fusion protein was used to subcutaneously immunize C57BL/6 mice, and NanAT1-TufT1-PlyD4 induced a strong and significant humoral immune response. The anti-NanAT1-TufT1-PlyD4 specific IgG antibody assays increased after the first immunization and reached the highest value at the 35th day. The results from in vitro experiments showed that anti-NanAT1-TufT1-PlyD4 antisera could inhibit the adhesion of Streptococcus pneumoniae (S. pneumoniae) to A549 cells. In addition, immunization with NanAT1-TufT1-PlyD4 significantly reduced S. pneumoniae colonization in the lung and decreased the damage to the lung tissues induced by S. pneumoniae infection. After challenge with a lethal dose of serotype 3 (NC_WCSUH32403), a better protection effect was observed with NanAT1-TufT1-PlyD4-immunized mice than with the separate full-length proteins and the adjuvant control; the survival rate was 50%, which met the standard of the marketed vaccine. Moreover, we showed that the humoral immune response and the Th1, Th2 and Th17-cellular immune pathways are involved in the immune protection of NanAT1-TufT1-PlyD4 to the host. Collectively, our results support that the novel fusion protein NanAT1-TufT1-PlyD4 exhibits extensive immune stimulation and is effective against pneumococcal challenges, and these properties are partially attributed to humoral and cellular-mediated immune responses.

Traditional Chinese Medical Journals currently published in mainland China.

BACKGROUND: Traditional Chinese Medical (TCM) journals have been playing an important role in scholarly communication in China. However, the information in those periodicals was not enough for international readers. OBJECTIVE: This study aims to provide an overview of TCM journals in China. METHODS: TCM journals currently published in mainland China were identified from Chinese databases and journal subscription catalogs. Data on publication start year, publishing region, language, whether core journals, whether indexed in famous international databases, with/without accessible URL were investigated, and subjects of journals were categorized. RESULTS: One hundred and forty-nine (149) TCM journals are currently published in mainland China; 88.59% of them are academic journals. The subjects of those journals are various, ranging from the general TCM, integrative medicine, herbal medicines, to veterinary TCM. The publishing areas are distributed in 27 regions, with Beijing having the most TCM journals published. One hundred and forty-two (142) of those periodicals are in Chinese, while 4 are also in English, and 3 in other languages. Only 8 TCM journals were recognized as core journals, and 5 were identified as both core journals and journals with high impacted articles by all evaluation systems in China. A few of the TCM journals from mainland China are indexed in PubMed/MEDLINE (10), EMBASE (5), Biological Abstracts (2), or AMED (1). Online full-text Chinese databases CJFD, COJ, and CSTPD cover most of TCM the journals published in the country. One hundred (100) TCM journals have accessible URLs, but only 3 are open access with free full texts. CONCLUSIONS: Publication of TCM journals in China has been active in academic communication in the past 20 years. However, only a few of them received recognized high evaluation. English information from them is not sufficient. Open access is not extensively acceptable. The accessibility of those journals to international readers needs to be improved.

Variations of chemical compositions in coarse aerosols and fine aerosols in two successive episodes.

Particulate matter with diameters less than 2.5 microm (PM2.5) and ranging between 10 to 2.5 microm (PM10-2.5) were simultaneously collected at four air-quality monitoring stations in the Taichung area of central Taiwan during the period of February 12 to 22, 2004. Two different types of PM10 episodes, a nonlocal dust-storm episode and a local episode, were observed in the present study. High concentrations of coarse aerosols occurred during the dust-storm episode, whereas high concentrations of fine aerosols were present during the local episode. Relatively high levels of Na+, Mg2+, Ca2+, and Cl- in coarse aerosols were observed during the dust-storm episode. Very high concentrations of secondary aerosols (NH4+, SO4(2-), and NO3-) in fine aerosols were observed during the local episode. The nitrate ion demonstrated the greatest increase in the ratios of ionic species to PM2.5 and ionic species to PM10-2.5 during the local episode. Significantly high ratios (0.444) of NO3- to NO2 in fine aerosols were present during the local episode, indicating that the relatively high formation rate of NO3 was one of the important factors leading to the increase of the NO3 to PM2.5 ratio during the local episode. Results also showed that an abundant quantity of fine ammonium nitrate was formed during the local episode, and chloride depletion probably was the major pathway to form coarse NaNO3 during this episode.