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Despite the outstanding technological advances achieved in the last few decades, infectious diseases remain a major societal challenge. From the variolation carried out in ancient China during the 15th century to the more advanced RNA and DNA vaccines presently available, vaccines have been proven as highly effective therapeutic tools to combat various infectious diseases. Vaccine research and development is now empowered with recent advances in Omics sciences and the developments of powerful bioinformatics tools. This Special Issue has gathered a total of nine original papers, including seven research papers and two reviews, illustrating the use of Omics data and bioinformatics in the research, design and development of vaccines against pathogens and cancer. The integration of knowledge from Omics and Bioinformatics will certainly boost vaccine research and development, leading to novel therapeutic tools against new and old pathogens and cancer in the near future. [ABSTRACT FROM AUTHOR]

After the policy adjustment, China no longer carries out COVID-19 PCR testing for all people, and antigen testing has become the main way to detect and manage infectious sources. We developed a dynamic model to evaluate and compare the effects between PCR and antigen testing for controlling the pandemic. Due to the increase of contact degree, the peak reduction effect of PCR testing in population is lower than that of antigen testing. Even if it was only 20% of people isolated at home after antigen testing, the peak of the epidemic could be reduced by 9.46%. If the proportion of antigen testing is further increased to 80%, the peak of the pandemic can be reduced by 31.41%. Antigen testing performed better effects in school (reduction proportion 29.27%) and community (29.34%) than in workplace (27.75%). Therefore, we recommend that antigen testing in the population should be encouraged during the pandemic, and home isolation of infected persons should be advocated, especially in crowded places. To improve the availability of antigen, the testing proportion should be further enhanced. [ABSTRACT FROM AUTHOR]

Background: Talaromycosis is one of the most common opportunistic infections in human immunodeficiency virus (HIV) infected patients. However, few researches have explored the prevalence in Southern China and fully assessed the value of the Mp1p antigen screening for the diagnosis of talaromycosis. Methodology/Principal findings: We performed a cross-sectional study of HIV-infected antiretroviral therapy (ART)-naïve adult patients who were seen in 2018 at Guangzhou Eighth People's Hospital, Guangzhou Medical University. Serum samples collected from all the 784 enrolled patients were tested for Mp1p antigen using double-antibody sandwich enzyme-linked immunosorbent assay. A culture of pathogen was conducted in 350 clinically suspected patients to confirm talaromycosis. The overall prevalence of talaromycosis based on the Mp1p antigen detection was 11.4% (89/784) and peaked at 32.2% (75/233) in patients with CD4+ ≤50 Nr/μl. Logistic regression analysis found Mp1p antigen positive rate decreased with the increase in CD4+ counts (OR 0.982, 95% CI 0.977–0.987, P<0.01). The optimal cut-off point of the CD4+ count was 50 Nr/μl or less. Among the 350 patients received both fungal culture and Mp1p antigen detection, 95/350 (27.1%) patients were culture-positive for a Talaromyces marneffei, 75/350 (21.4%) patients were Mp1p antigen positive. The Mp1p antigen assay showed a good agreement to the culture of pathogen, and the sensitivity, specificity, positive predictive value, negative predictive value and kappa value was 71.6% (68/95), 97.3% (248/255), 90.7% (68/75), 90.2% (248/275), and 0.737, respectively. The screening accuracy of the Mp1p antigen assay in patients with CD4+ counts of ≤50 Nr/μl was superior to that in those with higher CD4+ counts. Conclusions/Significance: Mp1p antigen screening can be an effective tool for more efficient diagnosis of Talaromycosis, especially in HIV/AIDS patients with low CD4+ counts. Future validation studies are needed. Author summary: Talaromyces marneffei (T. marneffei) is an important human immunodeficiency virus (HIV)-associated opportunistic pathogen in Southern China, and its infection is a leading cause of HIV-associated death. Properly and early antifungal treatment and timely antiretroviral therapy (ART) would reduce the mortality. Currently, the gold standard of diagnosis for talaromycosis is culture. The Mp1p antigen assay, the detection for a T. marneffei-specific protein, would be a reliable biomarker of T. marneffei infection in clinical practices. The CD4+ counts are an indicator of human immune system. The less CD4+ counts the weaker immune function and much possible the infection of opportunistic pathogen. In this study, we found that HIV patients with talaromycosis had a lower CD4+ count and more advanced disease compared to those without. The prevalence of talaromycosis based on the Mp1p antigen detection was significantly higher in patients with low CD4+ count than those with without. What's more, the Mp1p antigen screening was an effective tool to motivate the diagnosis for talaromycosis in patients with CD4+ ≤ 50 Nr/μl, and in turn to drive the initiation of antifungal treatment and ART, which would help the reduction of mortality and the improvement of treatment outcome. [ABSTRACT FROM AUTHOR]

Objective To assess the usefulness of serology as an indicator of Echinococcus transmission for developing preventive measures against echinococcosis in rural communities. Methods Cross-sectional survey in 2002 among 861 children aged 7 to 18 years in Xiji County, Ningxia, China. Before ultrasound abdominal examination, a questionnaire was used to identify socioeconomic, sanitary and hygiene risk factors for echinococcal infection; filter paper blood samples were collected from each child for specific antibody detection using EmP ( Echinococcus multilocularis) and EgB ( Echinococcus granulosus) antigens. Results Transmission of both E. multilocularis and E. granulosus occur in this area. Serological prevalence was far higher than disease prevalence in this age range. We found no gender-related differences of seroprevalence among the children, suggesting an equal chance of exposure to echinococcal egg-contaminated environments. The seroprevalence distribution was associated with changes in the ecology of wild hosts for E. multilocularis contamination, and with changes in socio-geographic features of the communities for E. granulosus contamination. Conclusions Serological data obtained for children in mass surveys of echinococcosis appear to be a comprehensive and useful tool to monitor changes of transmission dynamics in humans and provide ‘warning signals’ to decision makers for the instigation of specific control measures against the disease. [ABSTRACT FROM AUTHOR]

Introduction: The seeds of Brucea javanica (L.) Merr. (BJ) have been traditionally used to treat various types of cancers for many years in China. In this study, we systematically investigated a BJ oil emulsion (BJOE) produced from BJ seeds with the purpose of evaluating its antiviral effect against hepatitis B virus (HBV). Methods: HepG2.215 (a wild-type HBV cell line), HepG2, and Huh7, transfected with wildtype (WT) or lamivudine-resistance mutant (LMV-MT) HBV replicon plasmids, were treated with different doses of BJOE and then used for pharmacodynamic evaluation. Cell viability was determined using CCK8 assay. The levels of HBsAg/HBeAg in cell cultured supernatant, HBcAg in cell lysis solution, and HBV DNA in both were evaluated. Results: BJOE at =5 mg/ml was nontoxic to carcinoma cell lines, but could significantly inhibit WT/LMV-MT HBV replication and HBs/e/c antigen expression in a dose-dependent manner by upregulating interleukin-6 (IL-6), demonstrating that it possesses moderate anti-HBV activity. As one of the major components of BJOE, bruceine B was found to play a dominant role in IL-6 induction and HBV inhibition. Discussion: Our results demonstrated that BJOE suppressed HBV replication by stimulating IL-6, indicating that it has promising clinical therapeutic potential for both WT and LMV-MT HBV. [ABSTRACT FROM AUTHOR]

Background: Transmission-blocking vaccines (TBVs) target the sexual stages of malaria parasites to reduce or interrupt the transmission cycle in human and mosquito populations. The genetic diversity of TBVs candidate antigens, Pvs25 and Pvs28, in Plasmodium vivax could provide evidence for the development of TBVs. Methods: Dry blood spots from P. vivax patients were collected from Dandong, Suining, Hainan, Nyingchi, Tengchong, and Yingjiang in China. The pvs25 and pvs28 genes were amplified and sequenced. The genetic diversity of pvs25 and pvs28 were analyzed using DNASTAR, MEGA6, and DnaSP 5.0 programs. Results: A total of 377 samples were collected, among which 324 and 272 samples were successfully amplified in the pvs25 and pvs28 genes, respectively. Eight haplotypes were identified in Pvs25, for which the predominant mutation was I130T with 100% prevalence. A variety of 22 haplotypes in Pvs28 were identified. The number of GSGGE/D repeats of Pvs28 was a range of 4–8, among which, high (7–8) and low (4–5) copy numbers of tandem repeats were found in haplotypes H2 and H17, respectively. The nucleotide diversity of pvs28 (π = 0.00305 ± 0.00061) was slightly higher than that of pvs25 (π = 0.00146 ± 0.00007), thus they were not significantly different (P > 0.05). The Tajima's D value of pvs25 was positive whereas pvs28 was negative, which indicated that both genes were affected by natural selection. Conclusion: The genetic diversity of pvs25 and pvs28 genes in China was relatively limited, which provided valuable information for TBVs design and optimization. [ABSTRACT FROM AUTHOR]

Background: Providing RhD-negative red cell transfusions is a challenge in East Asia, represented by China, Korea, and Japan, where the frequency of RhD-negative is the lowest in the world.Findings: Among 56 ethnic groups in China, the RhD-negative frequency in Han, the prevalent ethnicity, is 0.5% or less, similar to most other ethnic groups. The Uyghur ethnic group has the highest reported RhD-negative frequency of up to 4.7%, as compared to 13.9% in the US. However, an estimated 7.15 million RhD-negative people live in China. The RhD-negative phenotype typically results from a loss of the entire RHD gene, causing the lack of the RhD protein and D antigen. The DEL phenotype carries a low amount of the D antigen and types as RhD-negative in routine serology. The DEL prevalence in RhD-negative individuals averages 23.3% in the Han, 17% in the Hui and 2.4% in the Uyghur ethnicities. The Asian type DEL, also known as RHD*DEL1 and RHD:c.1227G > A allele, is by far the most prevalent among the 13 DEL alleles observed in China.Conclusion: The purpose of this review is to summarize the data on DEL and to provide a basis for practical strategy decisions in managing patients and donors with DEL alleles in East Asia using molecular assays. [ABSTRACT FROM AUTHOR]

Background: Type 1 Diabetes (T1D) is a T cell-mediated autoimmune disorder caused by the destruction of insulin-secreting cells. B7-H3 (CD276) plays a vital role in T cell response. However, B7-H3 expression and its clinical significance in T1D remain unclear. The aim of this study was to investigate the correlations between the expression of B7-H3 and clinical parameters in T1D patients. The possible role of B7-H3 gene variants with T1D was also discussed. Methods: Four B7-H3 single nucleotide polymorphisms (SNPs) were genotyped in 121 T1D patients and 120 healthy controls by polymerase chain reaction (PCR) direct sequencing. Expression of membrane B7-H3 (mB7-H3) in peripheral blood lymphocytes was determined by flow cytometry. Levels of soluble B7-H3 (sB7-H3) in serum were analyzed by enzyme linked immunosorbent assay (ELISA). Results: The B7-H3 haplotype T-A-C-T was less frequently observed in T1D patients compared to the controls (OR: 0.31, 95% CI: 0.16–0.61). B7-H3 expression on monocytes showed significant upregulation in T1D patients and was positively correlated with several clinical features including ALT, fast C-peptide 120 min, HbAlc, IFN-γ, IL-6 and TNF-α (P < 0.05). The concentration of sB7-H3 in serum increased in T1D patients (P < 0.0001). We also observed that B7-H3-T-A-C-T was associated with the decreased release of sB7-H3 but not the membrane form. Conclusions: B7-H3 may act as a potential biomarker related to the pathogenesis of T1D. The B7-H3-T-A-C-T polymorphism variant is associated with the low risk of T1D as well as less release of sB7-H3. [ABSTRACT FROM AUTHOR]

Summary: Hepatocellular carcinoma (HCC) is the most common type of liver cancer with limited treatments. Asia has the highest HCC incidence rates; China accounts for over 50% of all HCC cases worldwide. T‐cell receptor (TCR) ‐engineered T‐cell immunotherapies specific for human leukocyte antigen (HLA) ‐A*02:01‐restricted α‐fetoprotein (AFP) peptide have shown encouraging results in clinics. HLA‐A*24:02 is more common than HLA‐A*02:01 in Asian countries, including China. Here we identified a novel HLA‐A*24:02‐restricted peptide KWVESIFLIF (AFP2–11) located in AFP signal peptide domain by mass spectrometric analysis of HLA‐bound peptides from HepG2 cells. A TCR (KWV3.1) specific for AFP2–11‐HLA‐A*24:02 was isolated from peripheral blood mononuclear cells of a healthy donor. The binding affinity of soluble KWV3.1 to its antigen was determined to be ~55 μm, within the affinity range of native TCRs for self‐antigens. KWV3.1‐transfected T cells could specifically activate and kill AFP2–11 pulsed T2‐A24 cells and AFP+ HLA‐A*24:02+ tumor cell lines, demonstrating that AFP2–11 can be naturally presented on the surface of AFP+ tumor cell lines. The newly identified antigenic peptide can provide a novel target for immunotherapeutic strategies for patients with AFP+ HLA‐A*24:02+ HCC. [ABSTRACT FROM AUTHOR]

Background. sCD30 and sCD26 are correlated with autoimmune diseases. However, little research has been done on the relationship between them and primary immune thrombocytopenia (ITP). Methods. This study enrolled 47 patients diagnosed with ITP in the Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences (Tianjin, China), from January 2015 to August 2015. The peripheral blood of all subjects was collected. The mRNA expression of CD30 was quantified by RT-PCR, and concentrations of sCD30 and sCD26 were measured by ELISA. Patient characteristics, CD30 mRNA levels, and sCD30 and sCD26 concentrations were analyzed. Results. The concentration of sCD30 was higher in active ITP patients (median, 35.82 ng/mL) than in remission ITP patients (median, 23.12 ng/mL; P = 0.021) and healthy controls (median, 25.11 ng/mL; P = 0.002). Plasma sCD26 levels decreased in remission ITP patients compared with that in healthy controls (median, 599.4 ng/mL vs. 964.23 ng/mL; P = 0.004). Ratios of sCD26/sCD30 in active ITP patients decreased compared with those in controls (P = 0.005). Increased sCD30 was positively correlated with hemorrhage (r = 0.493 , P = 0.017) in ITP patients while little relationship was identified between sCD26 and ITP. Conclusion. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity. [ABSTRACT FROM AUTHOR]

Abstract: The distribution of human leucocyte antigen (HLA) allele and haplotype varied among different ethnic populations. In this study, we investigated the allele and haplotype frequencies of HLA‐A, HLA‐B and HLA‐DRB1 loci in the Nanning Han population who live in Guangxi province of China. We identified 26 HLA‐A, 56 HLA‐B and 31 HLA‐DRB1 alleles in 562 Nanning individuals of Han ethnic group by sequence‐based typing method. Of these, the three most common alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (32.12%), A*02:07 (12.54%), A*24:02 (12.01%); B*46:01 (14.41%), B*15:02 (13.61%), B*40:01 (11.48%); DRB1*15:01 (14.15%), DRB1*16:02 (11.57%) and DRB1*12:02 (10.14%). With the exception of HLA‐DRB1, the p values of the HLA‐A and HLA‐B loci showed that the HLA allelic distribution in this population was in accordance with Hardy–Weinberg expectation (p > 0.05). A total of 173 HLA~A‐B~DRB1 haplotype with a frequency of >0.1% were presented and the three most common haplotype were HLA‐A*33:03~B*58:01~DRB1*03:01 (6.12%), HLA‐A*11:01~B*15:02~DRB1*12:02 (3.39%) and HLA‐A*11:01~B*15:02~DRB1*15:01 (3.22%). The phylogenetic tree and the principal component analysis suggested that Nanning Han population had a relative close genetic relationship with Chinese Zhuang population and a relative distant genetic relationship with Northern Han Chinese. The information will be useful for anthropological studies, for HLA matching in transplantation and disease association studies in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL.Methods: Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration.Results: Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR.Conclusions: This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures are taken to reduce hepatic and cardiovascular toxicity. In addition to IPI and tumor diameter, HBsAg positivity could also be a poor prognostic factor for CR in Chinese patients with DLBCL.Trial Registration: ClinicalTrials.gov # NCT01340443 , April 20, 2011. [ABSTRACT FROM AUTHOR]

In 2013, the first case of human infection with an avian influenza A virus (H7N9) was reported in China, and the human infection with this virus has continued as of 2016. At the request of the WHO, we have successfully developed candidate reassortant vaccine virus using A/Anhui/1/2013 and the high egg-growth master virus A/PR/8/1934. Recent plans regarding influenza vaccine production include using cell-cultured systems in Japan and several other countries. However, egg-based vaccine viruses are not always suitable for cell-cultured vaccine production due to potential issues with growth, protein yield and antigenic stability. Therefore, in this study, we have developed a high-growth master virus (hg-PR8) adapted to qualified NIID-MDCK cells that are competent for vaccine production. The virus hg-PR8 was obtained after 20 serial passages of A/Puerto Rico/8/1934 (PR8) in NIID-MDCK cells. The viral titer of hg-PR8 was 108.6 plaque-forming units per milliliter (PFU/mL). Seven amino acid substitutions were identified in the amino acid sequences of PB2, PB1, PA, NA, M and NS of hg-PR8 compared to the sequence of the original PR8 (org-PR8) strain. The growth capacities of the reassortant viruses, which possess heterologous internal genes from hg-PR8 or org-PR8, indicated that the amino acid changes in PB2 and NS2 similarly affected growth capacity in NIID-MDCK cells. To assess the suitability of hg-PR8 as a master virus, we generated 6:2 reassortant viruses possessing the HA and NA segments from A/Anhui/1/2013 (H7N9) and the remaining segments from hg-PR8. The virus titers of the reassortant strains were 107−108 PFU/mL. The antigenicity of the viruses was stable during ten passages of the viruses in NIID-MDCK cells. In comparison with the egg-based reassortant vaccine viruses with identical HA and NA segments, the hg-PR8-based viruses showed 1.5- to 2-fold higher protein yields in NIID-MDCK cells. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis (VL) is a life-threatening disease caused by protozoan parasites of the Leishmania donovani complex. Early case detection followed by adequate treatment is essential to the control of VL. However, the available diagnostic tests are either invasive and require considerable expertise (parasitological demonstration of the parasite in tissue smears) or unable to distinguish between past and active infection (serological methods). Therefore, we aimed to develop a lateral flow assay in the form of an immunochromatographic test (ICT) device based on the detection of a circulating Leishmania antigen using monoclonal antibodies (mAbs). Methodology/Principal Findings: mAbs were produced by fusion of murine myeloma cells with splenocytes isolated from a mouse immunized with L. donovani soluble crude antigen. Out of 12 cloned hybridoma cell lines, two secreted mAbs recognizing the same leishmanial protein. These mAbs were used to produce an ICT as a sandwich assay for the detection of circulating antigen in serum and blood samples. The ICT was evaluated with 213 serum samples from VL patients living in VL endemic areas in China, and with 156 serum samples from patients with other diseases as well as 78 serum samples from healthy donors. Sensitivity, specificity and diagnostic efficiency of the new ICT was 95.8%, 98.7% and 97.3%, respectively. Compared with a commercially available antibody detecting ICT, our antigen-based ICT performed slightly better. Conclusion/Significance: The newly developed ICT is an easy to use and more accurate diagnostic tool which fulfils the performance and operational characteristics required for VL case detection under field and laboratory conditions. As our ICT detects a circulating antigen, it will also be useful in monitoring treatment success and diagnosing VL in immunocompromised patients. Author Summary: Visceral leishmaniasis is a neglected disease caused by different species of protozoan parasites of the genus Leishmania. The disease is endemic in 61 countries, and in many of them it poses a serious public health issue. As visceral leishmaniasis is fatal if left untreated, early diagnosis is essential for treatment and control of the disease. Current available diagnostic tests are either difficult to carry out under field conditions or insufficiently accurate. In this study we developed a new diagnostic test which detects a circulation parasite-derived antigen in serum or blood samples of patients with visceral leishmaniasis. We found that our test performed better than most other tests based on the detection of parasite-specific antibodies. In addition, as our test is a device for the detection of an acute infection, it will be useful to validate treatment and in the diagnosis of the disease in patients with deficient antibody production (as in AIDS patients). [ABSTRACT FROM AUTHOR]

Background: Since human infection with the novel H7N9 avian influenza virus was identified in China in March 2013, the relatively high mortality rate and possibility of human-to-human transmission have highlighted the urgent need for sensitive and specific assays for diagnosis of H7N9 infection. Methodology/Principal Findings: We developed a rapid diagnostic test for the novel avian influenza A (H7N9) virus using anti-hemagglutinin (HA) monoclonal antibodies specifically targeting H7 in an immunochromatographic assay system. The assay limit of detection was 103.5 pfu/ml or 103TCID50 of H7N9 virus. The assay specifically detected H7N9 viral isolates and recombinant HA proteins of H7 subtypes including H7N7 and H7N9, but did not react with non-H7 subtypes including H1N1, H3N2, H5N1, H5N9, and H9N2. The detection sensitivity was 59.4% (19/32) for H7N9 patients confirmed by RT-PCR. Moreover, the highest sensitivity of 61.5% (16/26) was obtained when testing H7N9 positive sputum samples while 35.7% (5/14) of nasopharyngeal swabs and 20% (2/10) of fecal samples tested positive. No false positive detection was found when testing 180 H7N9 negative samples. Conclusions/Significance: Our novel rapid assay can specifically detect H7 HA antigen, facilitating rapid diagnosis for prevention and control of the on-going H7N9 epidemic. [ABSTRACT FROM AUTHOR]

The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10−6). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10−13). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10−13) and -negative RA (P = 3.89×10−5). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a contagious disease affected by multiple genetic and environmental factors. Several association studies have suggested that cellular immune response is vital for controlling and preventing of tuberculosis infection. Low molecular weight polypeptides (LMPs) and transporters with antigen processing (TAPs) are the main molecules in the processing and presentation pathway for intracellular antigens. This study was performed to elucidate whether these antigen-processing genes (LMP/TAP) polymorphisms could be associated with the risk of tuberculosis infection in China. Methodology/Principal Findings: We recruited 205 active pulmonary tuberculosis patients and 217 normal controls from Li population for this study. Four polymorphisms of LMP/TAP genes were determined by PCR-RFLP assay and haplotypes were constructed by software PHASE 1.0. Of the total four polymorphisms, genotype frequencies of LMP7 AA homozygote and CA heterozygote were significantly greater among cases compared to controls, with odds ratio of 3.77 (95% CI: 1.60-8.89; P = 0.002) and 2.97 (95% CI: 1.80-4.90; P<0.0001), respectively. The genotypes of TAP1-2 GG homozygote and AG heterozygote were more frequent in subjects with TB than in controls, with odds ratio of 3.94 (95% CI: 1.82-8.53; P = 0.001) and 2.87 (95% CI: 1.75-4.71; P<0.0001), respectively. Similarly, we found that haplotype B which carried LMP7 and TAP1-2 variations significantly increased the susceptibility to TB (OR = 3.674, 95% CI: 2.254-5.988; P<0.0001). Moreover, it is noteworthy that the homozygote of wild haplotype A (A/A) may be a strong protection for TB infection. Conclusions: Our findings suggested that LMP/TAP gene polymorphisms might be risk factors for TB infection among Li population in China. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC) molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. Methodology/Principal Findings: Promoters (nirB or pagC) were used to express the antigen (Sj23LHDGST) and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE1–104-Sj23LHD-GST) efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. Conclusion/Significance: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development. Author Summary: Schistosomiasis japonica is a zoonotic parasitic disease and occurs predominantly in Southeast Asia and China. Using a simple, cheap, yet efficient oral method to deliver the vaccine antigen would benefit to control its transmission in that the oral vaccine could be made into a preparation and mixed with feedstuffs of livestock hosts. In this study, we used an attenuated S. typhimurium strain VNP20009, whose safety has been demonstrated in phase I clinical trial, to express the bivalent Schistosoma japonicum antigen Sj23LHD-GST by an intracellular activated promoter (nirB) and deliver it to host cells through type III secretion system. After oral vaccination of this recombinant strain, efficient protection against S. japonicum challenge was induced in mice. Mean while, granuloma formation in the liver was improved significantly in the immunized mice. This protective immune response was Th1 specific type as evidenced by increase in the production of IL-12 and IFN-γ. This work provides an alternative S. japonicum vaccine for livestock and humans. [ABSTRACT FROM AUTHOR]

A critical step for avian influenza viruses to infect human hosts and cause epidemics or pandemics is acquisition of the ability of the viral hemagglutinin (HA) to bind to human receptors. However, current global influenza surveillance does not monitor HA binding specificity due to a lack of rapid and reliable assays. Here we report a computational method that uses an effective scoring function to quantify HA-receptor binding activities with high accuracy and speed. Application of this method reveals receptor specificity changes and its temporal relationship with antigenicity changes during the evolution of human H3N2 viruses. The method predicts that two amino acid differences at 222 and 225 between HAs of A/Fujian/411/02 and A/Panama/2007/99 viruses account for their differences in binding to both avian and human receptors; this prediction was verified experimentally. The new computational method could provide an urgently needed tool for rapid and largescale analysis of HA receptor specificities for global influenza surveillance. [ABSTRACT FROM AUTHOR]

Background: Antigen B (EgAgB) is a major protein produced by the metacestode cyst of Echinococcus granulosus, the causative agent of cystic hydatid disease. This protein has been shown to play an important role in modulating host immune responses, although its precise biological function still remains unknown. It is generally accepted that EgAgB is comprised of a gene family of five subfamilies which are highly polymorphic, but the actual number of genes present is unknown. Methodology/Principal Findings: Based on published sequences for the family, we designed specific primers for each subfamily and used PCR to amplify them from genomic DNA isolated from individual mature adult worms (MAW) taken from an experimentally infected dog in China and individual larval protoscoleces (PSC) excised from a single hydatid cyst taken from an Australian kangaroo. We then used real-time PCR to measure expression of each of the genes comprising the five EgAgB subfamilies in all life-cycle stages including the oncosphere (ONC). Conclusions/Significance: Based on sequence alignment analysis, we found that the EgAgB gene family comprises at least ten unique genes. Each of the genes was identical in both larval and adult E. granulosus isolates collected from two geographical areas (different continents). DNA alignment comparisons with EgAgB sequences deposited in GenBank databases showed that each gene in the gene family is highly conserved within E. granulosus, which contradicts previous studies claiming significant variation and polymorphism in EgAgB. Quantitative PCR analysis revealed that the genes were differentially expressed in different life-cycle stages of E. granulosus with EgAgB3 expressed predominantly in all stages. These findings are fundamental for determining the expression and the biological function of antigen B. [ABSTRACT FROM AUTHOR]

Host genetic factors and environment factors including hepatitis B virus (HBV) genotype are widely viewed as common basis of the different outcomes of HBV infection. Human leucocyte antigen (HLA) plays an important role in immunological reaction to HBV infection. The study aimed to explore whether the HLA-DQB1 allele polymorphisms are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and thirty-four asymptomatic HBV carriers and 139 chronic hepatitis B patients were recruited in this case-control study in Beijing, China. Sequence-specific primers–polymerase chain reaction was used to detect 13 alleles of HLA-DQB1 gene. The frequency distributions of alleles in two groups were analysed using SAS 9.1.2 software. After adjustment of confounders the frequencies of HLA-DQB1*0503 allele and *0303 allele in chronic hepatitis B group were statistically significant lower than those in asymptomatic HBV carrier group (P = 0.04; P = 0.05), and the frequency of exposure to alcohol consumption in patients with chronic hepatitis B was clearly higher than that in asymptomatic HBV carrier group (P = 0.004). HLA-DQB1*0503 allele and *0303 allele are independently resistant genetic factors to chronic hepatitis B, and alcohol consumption is the risk factor of chronic hepatitis B. [ABSTRACT FROM AUTHOR]

Background: Echinococcoses, caused by metacestodes of Echinococcus granulosus (cystic echinococcosis; CE) and E. multilocularis (alveolar echinococcosis; AE), represent major emerging parasitic diseases. These enzootic helminthiases invoke significant public health concerns and social burdens in endemic areas. The diseases are prevalent in the Qinghai-Tibetan Plateau, China, while community-based epidemiological studies have been scarcely reported. We surveyed echinococcosis patients in the southeastern Qinghai Province, China, to better understand the concurrent epidemiological situation in this area. Methods: During July and August of 2013 and 2014, we screened echinococcosis patients at Yushu and Golog Prefectures, Qinghai Province, China, in a diagnostic campaign. A total of 2856 people (male:female ratio, 1:1.12; mean age, 34.6 years; age range, 6–88 years) were ultrasonographically examined for the presence of hepatic echinococcal cysts. We also collected serum samples from patients and analyzed antibody reactivity against recombinant forms of diverse E. granulosus antigen Bs (rEgAgB1-5) by enzyme-linked immunosorbent assay. Results: We detected 134 patients whose imaging scans were compatible with CE (115 cases) and AE (20 patients). One patient might have been infected with both CE and AE. The overall incidence was 4.7% (CE, 4.0%; AE, 0.7%). A large proportion (67.5%) of CE patients was diagnosed at active and transitional CE1-CE3 stages in their late 30s. The AE cases were generally detected at advanced stage in patients at early 20s (60%). Analysis of the receiver operating characteristic curve and Youden's index indicated that rEgAgB2 was the most promising biomarker, followed by rEgAgB3 and rEgAgB1. Overall, sensitivity and specificity of rEgAgB1-3 were 84.5–92.7% and 91.9–94.6%, respectively. rEgAgB4 and 5 showed low sensitivity with high cross-reactivity. Conclusions: Our results strongly suggest that disability-adjusted life years related to echinococcoses in Qinghai-Tibetan areas might be more serious than previously considered. Control and prevention strategy against CE and AE are highly required in these areas. In addition to ultrasonography, serological tests might provide supportive data. However, serological data should be carefully interpreted for differential diagnosis, especially in areas where both CE and AE are co-endemic. [ABSTRACT FROM AUTHOR]