Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-27 (of 27 Records) |
Query Trace: Miao C[original query] |
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Predictors of Five-Year Persistence of Antibody Responses to Zoster Vaccines
Weinberg A , Schmid DS , Leung J , Johnson MJ , Miao C , Levin MJ . J Infect Dis 2023 BACKGROUND: Protection against herpes zoster (HZ) is primarily conferred by cell-mediated immunity (CMI). However, anti-VZV-glycoprotein (anti-gp) antibody responses to Zoster Vaccine Live (ZVL) correlate with protection, suggesting a potential protective role for antibody. Detailed studies of antibody responses to the Recombinant Zoster Vaccine (RZV) are lacking. METHODS: We compared ELISA-measured anti-gp and anti-glycoprotein E (anti-gE) antibodies and avidity in 159 participants randomized to RZV (n = 80) or ZVL (n = 79) recipients over 5 years post-vaccination and identified predictors of antibody persistence. RESULTS: The comparison between vaccine groups showed higher anti-gE and anti-gp antibody levels after RZV than ZVL over the 5-year study duration. RZV recipients also had higher anti-gE avidity for 5 years and higher anti-gp avidity in the first year post-vaccination. Compared with pre-vaccination, RZV recipients maintained higher levels of anti-gE antibodies and avidity for 5 years, whereas ZVL recipients only maintained higher anti-gE avidity. Anti-gp antibody levels and avidity decreased to pre-vaccination levels or below after 1-year post-vaccination in both groups. Independent predictors of persistence of antibody levels and avidity were the following: vaccine type, pre-vaccination and peak antibody levels and avidity, pre-vaccination and peak CMI, and age. Sex or prior ZVL administration did not affect persistence. CONCLUSION: Antibody responses and avidity were higher and more persistent in RZV than ZVL recipients. The effect of age on antibody persistence in RZV recipients is novel. |
Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster
Laing KJ , Ouwendijk WJD , Campbell VL , McClurkan CL , Mortazavi S , Elder Waters M , Krist MP , Tu R , Nguyen N , Basu K , Miao C , Schmid DS , Johnston C , Verjans Gmgm , Koelle DM . Nat Commun 2022 13 (1) 6957 Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin. |
Humoral and cellular immune responses to recombinant herpes zoster vaccine in patients with chronic lymphocytic leukemia and monoclonal B cell lymphocytosis
Muchtar E , Koehler AB , Johnson MJ , Rabe KG , Ding W , Call TG , Leis JF , Kenderian SS , Hayman SR , Wang Y , Hampel PJ , Holets MA , Darby HC , Slager SL , Kay NE , Miao C , Canniff J , Whitaker JA , Levin MJ , Schmid DS , Kennedy RB , Weinberg A , Parikh SA . Am J Hematol 2021 97 (1) 90-98 Monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B cell disorders associated with increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by two months. Responses assessed at 3-months and 12-months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color IFN-γ and IL-2 FLUOROSPOT assays were compared to historic controls matched by age and sex. Sixty-two patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, P=0.03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs 36%, respectively, P=0.23). The CD4+ T cell response to vaccination was significantly lower in study participants compared to controls (54% vs 96%, P<0.001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs 73%, P=0.008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n=47), 24% had antibody titers below response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed. This article is protected by copyright. All rights reserved. |
Comparative antibody responses to the live-attenuated and recombinant herpes zoster vaccines
Schmid DS , Miao C , Leung J , Johnson M , Weinberg A , Levin MJ . J Virol 2021 95 (12) Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): 1) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV), and 2) recombinant adjuvanted vaccine (RZV) containing recombinant VZV glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status.VZV T cell-mediated immunity (CMI), but not humoral immunity, are considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination [19 and 12 avidity index units (AIU), respectively]. RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost: 47 AIU versus 22 AIU; mean neutralizing antibody boost: 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r=0.5) and moderately with gp avidity increases (r=0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses.IMPORTANCEThese observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity, neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Finally, combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development could benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials. |
Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptors
Wu BC , Olivia NA , Tembo JM , He YX , Zhang YM , Xue Y , Ye CL , Lv Y , Li WJ , Jiang LY , Huo XX , Sun ZY , Chen ZJ , Qin JC , Li AY , Park CG , Klena JD , Ding HH , Chen T . J Med Microbiol 2021 70 (3) ![]() Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors. |
Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients
Hirzel C , L'Huillier AG , Ferreira VH , Marinelli T , Ku T , Ierullo M , Miao C , Schmid DS , Juvet S , Humar A , Kumar D . Am J Transplant 2021 21 (6) 2246-2253 Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n=43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p<0.0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p<0.0001). gE-specific polyfunctional CD4+ T-cell frequencies (n=38) also increased from baseline (median 85 per 10(6) CD4+ T-cells; IQR: 46-180) to the first (median 128 per 10(6) CD4+ T-cells; IQR: 82-353; p=0.023) and after the second dose (median 361 per 10(6) CD4+ T-cells; IQR: 146-848; p<0.0001). Tenderness (83.0%; 95%CI:69.2-92.4%) and redness (31.9%; 95%CI:19.1-47.1%) at injection site were common. One rejection episode within three weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population. |
Evaluation of recombinant herpes zoster vaccine for primary immunization of varicella-seronegative transplant recipients
LʼHuillier AG , Hirzel C , Ferreira VH , Ierullo M , Ku T , Selzner N , Schiff J , Juvet S , Miao C , Schmid DS , Humar A , Kumar D . Transplantation 2021 105 (10) 2316-2323 BACKGROUND: Immunization of VZV-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection. METHODS: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 months apart. Blood was drawn prevaccination (V1), prior to the second dose (V2) and 4 weeks after second dose (V3). Humoral (anti-gE) and cell-mediated immunity was evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines. RESULTS: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 years and median time since transplant procedure was 38 years. The most frequent transplant types were liver (35%) and lung (30%). Median anti-gE levels significantly increased from V1 to V3 (p=0001) and V2 to V3 (p<0001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cells counts increased from V1 to V2 (54/10 vs 104/10 cells; p=0041), and from V2 to V3 (380/10; p=0002). Most adverse events were mild with no rejection episodes. CONCLUSION: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients, and has the potential to be considered as a preventive strategy against primary varicella. |
Childhood polybrominated diphenyl ether (PBDE) serum concentration and reading ability at ages 5 and 8 years: The HOME Study
Liang H , Vuong AM , Xie C , Webster GM , Sjodin A , Yuan W , Miao M , Braun JM , Dietrich KN , Yolton K , Lanphear BP , Chen A . Environ Int 2019 122 330-339 BACKGROUND: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment and human beings. PBDE concentrations are higher in children than adults. A previous study found that prenatal PBDE exposure was associated with decreased reading skills in children; however, evidence is limited on the potential impact of childhood exposure to PBDEs. The study examined the association between childhood PBDE exposures and reading ability in children at ages 5 and 8years. METHODS: The study included 230 children from an ongoing prospective pregnancy and birth cohort study, the Health Outcomes and Measures of Environment (HOME) Study, conducted in Cincinnati, Ohio. Children's serum concentrations of eleven PBDE congeners were measured at 1, 2, 3, 5, and 8years. The Woodcock-Johnson Tests of Achievement - III and the Wide Range Achievement Test - 4 were administered to assess children's reading skills at ages 5 and 8years, respectively. We used multiple informant models to examine the associations between repeated measures of PBDEs and reading scores at ages 5 and 8years. We also estimated the betas and 95% CIs of the association of PBDE measure at each age by including interaction terms between PBDE concentrations and child age in the models. RESULTS: All childhood BDE-153 concentrations were inversely associated with reading scores at 5 and 8years, but associations were not statistically significant after covariate adjustment. For example, a 10-fold increase in BDE-153 concentrations at ages 3 and 5years was associated with a -5.0 (95% confidence interval (CI): -11.0, 1.0) and -5.5 (95% CI: -12.5, 1.4) point change in Basic Reading score at age 5years, respectively. Similarly, the estimates for Brief Reading score at age 5years were -4.5 (95% CI: -10.5, 1.5) and -5.2 (95% CI: -12.2, 1.7) point changes, respectively. Serum concentration of BDE-47, -99, -100, and Sum4PBDEs (sum of BDE-47, 99, 100, and 153) at every age were inversely associated with reading scores at ages 5 and 8years in unadjusted analyses. While the adjusted estimates were much attenuated and became non-significant, the direction of most of the associations was not altered. CONCLUSION: Our study has shown a suggestive but non-significant trend of inverse associations between childhood PBDE serum concentrations, particularly BDE-153, and children's reading skills. Future studies with a larger sample size are needed to examine these associations. |
Development and evaluation of a multiplexed immunoassay for simultaneous detection of serum IgG antibodies to six human coronaviruses
Trivedi SU , Miao C , Sanchez JE , Caidi H , Tamin A , Haynes L , Thornburg NJ . Sci Rep 2019 9 (1) 1390 Known human coronaviruses (hCoV) usually cause mild to moderate upper-respiratory tract illnesses, except SARS-CoV and MERS-CoV, which, in addition to mild illness can also be associated with severe respiratory diseases and high mortality rates. Well-characterized multiplexed serologic assays are needed to aid in rapid detection and surveillance of hCoVs. The present study describes development and evaluation of a multiplexed magnetic microsphere immunoassay (MMIA) to simultaneously detect immunoglobulin G (IgG) antibodies specific for recombinant nucleocapsid proteins (recN) from hCoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV. We used paired human sera to screen for IgG with reactivity against six hCoVs to determine assay sensitivity, specificity and reproducibility. We found no signal interference between monoplex and multiplex assay formats (R(2) range = 0.87-0.97). Screening of paired human sera using MMIA, resulted in 92 of 106 (sensitivity: 86%) as positive and 68 of 80 (specificity: 84%) as negative. This study serves as a proof of concept that it is feasible to develop and use a multiplexed microsphere immunoassay as a next generation screening tool for use in large scale seroprevalence studies of hCoVs. |
Serologic follow-up of Middle East Respiratory Syndrome coronavirus cases and contacts - Abu Dhabi, United Arab Emirates
Al Hosani FI , Kim L , Khudhair A , Pham H , Al Mulla M , Al Bandar Z , Pradeep K , Elkheir KA , Weber S , Khoury M , Donnelly G , Younis N , El Saleh F , Abdalla M , Imambaccus H , Haynes LM , Thornburg NJ , Harcourt JL , Miao C , Tamin A , Hall AJ , Russell ES , Harris AM , Kiebler C , Mir RA , Pringle K , Alami NN , Abedi GR , Gerber SI . Clin Infect Dis 2018 68 (3) 409-418 Background: Although there is evidence of person-to-person transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent that disease severity affects transmission. Methods: A sero-epidemiological investigation was conducted among Middle East Respiratory Syndrome Coronavirus (MERS-CoV) case-patients and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. Cases diagnosed between January 1, 2013-May 9, 2014 and their household contacts were approached for enrollment. Demographic, clinical, and exposure history data were collected. Sera were screened by MERS-CoV nucleocapsid protein (N) ELISA and indirect immunofluorescence, with results confirmed by microneutralization assay. Results: Ninety-one percent (n=31/34) of case-patients were asymptomatic or mildly symptomatic and did not require oxygen during hospitalization. MERS-CoV antibodies were detected in 13 of 24 (54%) cases with available sera, including 3 asymptomatic, 9 mildly symptomatic, and 1 severely symptomatic case-patient. No serologic evidence of MERS-CoV transmission was found among 105 household contacts with available sera. Conclusions: Transmission of MERS-CoV was not documented in this investigation of mostly asymptomatic and mildly symptomatic cases and their household contacts. These results have implications for clinical management of cases and formulation of isolation policies to reduce the risk of transmission. |
Anti-respiratory syncytial virus (RSV) G monoclonal antibodies reduce lung inflammation and viral lung titers when delivered therapeutically in a BALB/c mouse model
Caidi H , Miao C , Thornburg NJ , Tripp RA , Anderson LJ , Haynes LM . Antiviral Res 2018 154 149-157 RSV continues to be a high priority for vaccine and antiviral drug development. Unfortunately, no safe and effective RSV vaccine is available and treatment options are limited. Over the past decade, several studies have focused on the role of RSV G protein on viral entry, viral neutralization, and RSV-mediated pathology. Anti-G murine monoclonal antibody (mAb) 131-2G treatment has been previously shown to reduce weight loss, bronchoalveolar lavage (BAL) cell number, airway reactivity, and Th2-type cytokine production in RSV-infected mice more rapidly than a commercial humanized monoclonal antibody (mAb) against RSV F protein (Palivizumab). In this study, we have tested two human anti-RSV G mAbs, 2B11 and 3D3, by both prophylactic and therapeutic treatment for RSV in the BALB/c mouse model. Both anti-G mAbs reduced viral load, leukocyte infiltration and IFN-gamma and IL-4 expression in cell-free BAL supernatants emphasizing the potential of anti-G mAbs as anti-inflammatory and antiviral strategies. |
Conveyance contact investigation for imported Middle East Respiratory Syndrome cases, United States, May 2014
Lippold SA , Objio T , Vonnahme L , Washburn F , Cohen NJ , Chen TH , Edelson PJ , Gulati R , Hale C , Harcourt J , Haynes L , Jewett A , Jungerman R , Kohl KS , Miao C , Pesik N , Regan JJ , Roland E , Schembri C , Schneider E , Tamin A , Tatti K , Alvarado-Ramy F . Emerg Infect Dis 2017 23 (9) 1585-1589 In 2014, the Centers for Disease Control and Prevention conducted conveyance contact investigations for 2 Middle East respiratory syndrome cases imported into the United States, comprising all passengers and crew on 4 international and domestic flights and 1 bus. Of 655 contacts, 78% were interviewed; 33% had serologic testing. No secondary cases were identified. |
Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection
Trivedi S , Miao C , Al-Abdallat MM , Haddadin A , Alqasrawi S , Iblan I , Nsour MA , Alsanouri T , Sheikh Ali S , Rha B , Gerber SI , Payne DC , Tamin A , Thornburg NJ . J Med Virol 2017 90 (2) 367-371 The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS-CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or microneutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS-CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus. |
Persistence of antibodies against Middle East Respiratory Syndrome coronavirus
Payne DC , Iblan I , Rha B , Alqasrawi S , Haddadin A , Al Nsour M , Alsanouri T , Ali SS , Harcourt J , Miao C , Tamin A , Gerber SI , Haynes LM , Al Abdallat MM . Emerg Infect Dis 2016 22 (10) 1824-6 To determine how long antibodies against Middle East respiratory syndrome coronavirus persist, we measured long-term antibody responses among persons serologically positive or indeterminate after a 2012 outbreak in Jordan. Antibodies, including neutralizing antibodies, were detectable in 6 (86%) of 7 persons for at least 34 months after the outbreak. |
Leveraging health-related quality of life in population health management: the case for Healthy Days
Slabaugh SL , Shah M , Zack M , Happe L , Cordier T , Havens E , Davidson E , Miao M , Prewitt T , Jia H . Popul Health Manag 2016 20 (1) 13-22 Measuring population health with morbidity and mortality data, often collected at the site of care, fails to capture the individual's perspective on health and well-being. Because health happens outside the walls of medical facilities, a holistic and singular measure of health that can easily be captured for an entire population could aid in understanding the well-being of communities. This paper postulates that Healthy Days, a health-related quality of life measure developed and validated by the Centers for Disease Control and Prevention, is an ideal survey instrument to advance population health. A systematic literature review was conducted and revealed a strong evidence base using Healthy Days with significant correlations to chronic disease conditions. Building on the literature base and experience, methods for analyzing Healthy Days data are discussed, including stratified sampling techniques, statistical measures to account for variance, and modeling techniques for skewed distributions. Using such analytic techniques, Healthy Days has been used extensively in national health surveillance. As the health care system faces increasing costs and constrained resources, the Healthy Days survey instrument can be used to inform public policies and allocate health service resources. Because Healthy Days captures broad dimensions of health from the individual's perspective, it is a simple way to holistically measure the health and well-being of a population and its trend over time. Expanded use of Healthy Days can aid population health managers and contribute to the understanding of the broader determinants of the nation's and individual community's health and aid in evaluating progress toward health goals. (Population Health Management 2016;xx:xxx-xxx). |
Multifacility Outbreak of Middle East Respiratory Syndrome in Taif, Saudi Arabia.
Assiri A , Abedi GR , Saeed AA , Abdalla MA , Al-Masry M , Choudhry AJ , Lu X , Erdman DD , Tatti K , Binder AM , Rudd J , Tokars J , Miao C , Alarbash H , Nooh R , Pallansch M , Gerber SI , Watson JT . Emerg Infect Dis 2016 22 (1) 32-40 ![]() Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014-January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices. |
An economic analysis of adult hepatitis B vaccination in China
Zheng H , Wang FZ , Zhang GM , Zhou F , Cui FQ , Wu ZH , Miao N , Sun XJ , Li L , Liang XF . Vaccine 2015 33 (48) 6831-9 BACKGROUND AND OBJECTIVE: With the universal infant hepatitis B vaccination (HepB) program, China has made remarkable achievements to prevent and control hepatitis B. In order to further reduce hepatitis B virus (HBV) infection, the Chinese government is considering implementing a widespread adult HBV vaccination campaign. We performed an economic analysis of two different adult HepB vaccination strategies for 21-59-years-olds: vaccination without screening and screening-based vaccination. METHODS: Cost-benefit analyses were conducted. All 21-59-year-olds were divided into two groups: young adults (ages 21-39) and middle-aged adults (ages 40-59). Costs and benefits were estimated using the direct cost and societal (direct and indirect costs) perspectives. All costs and benefits were adjusted to 2014 US dollars, where future values were discounted at a 3% annual rate. We calculated benefit-cost ratios (BCRs) of the two vaccination strategies for the two different age groups. Sensitivity analyses varied key parameters within plausible ranges. RESULTS: Among young adults, the direct and societal BCRs for a vaccination campaign with no screening would be 1.06 and 1.42; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 1.19 and 1.73. Among middle-aged adults, the direct and societal BCRs for a vaccination campaign without screening would be 0.59 and 0.59; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 0.68 and 0.73. CONCLUSION: The results of our study support a HepB vaccination campaign for young adults. Additionally, a vaccination campaign with screening appeared to provide greater value than a vaccination without screening. |
Family cluster of Middle East respiratory syndrome coronavirus infections, Tunisia, 2013
Abroug F , Slim A , Ouanes-Besbes L , Kacem MA , Dachraoui F , Ouanes I , Lu X , Tao Y , Paden C , Caidi H , Miao C , Al-Hajri MM , Zorraga M , Ghaouar W , BenSalah A , Gerber SI . Emerg Infect Dis 2014 20 (9) 1527-30 ![]() In 2013 in Tunisia, 3 persons in 1 family were infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The index case-patient's respiratory tract samples were negative for MERS-CoV by reverse transcription PCR, but diagnosis was retrospectively confirmed by PCR of serum. Sequences clustered with those from Saudi Arabia and United Arab Emirates. |
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Wang Z , Zhu B , Zhang M , Parikh H , Jia J , Chung CC , Sampson JN , Hoskins JW , Hutchinson A , Burdette L , Ibrahim A , Hautman C , Raj PS , Abnet CC , Adjei AA , Ahlbom A , Albanes D , Allen NE , Ambrosone CB , Aldrich M , Amiano P , Amos C , Andersson U , Andriole G Jr , Andrulis IL , Arici C , Arslan AA , Austin MA , Baris D , Barkauskas DA , Bassig BA , Beane Freeman LE , Berg CD , Berndt SI , Bertazzi PA , Biritwum RB , Black A , Blot W , Boeing H , Boffetta P , Bolton K , Boutron-Ruault MC , Bracci PM , Brennan P , Brinton LA , Brotzman M , Bueno-de-Mesquita HB , Buring JE , Butler MA , Cai Q , Cancel-Tassin G , Canzian F , Cao G , Caporaso NE , Carrato A , Carreon T , Carta A , Chang GC , Chang IS , Chang-Claude J , Che X , Chen CJ , Chen CY , Chen CH , Chen C , Chen KY , Chen YM , Chokkalingam AP , Chu LW , Clavel-Chapelon F , Colditz GA , Colt JS , Conti D , Cook MB , Cortessis VK , Crawford ED , Cussenot O , Davis FG , De Vivo I , Deng X , Ding T , Dinney CP , Di Stefano AL , Diver WR , Duell EJ , Elena JW , Fan JH , Feigelson HS , Feychting M , Figueroa JD , Flanagan AM , Fraumeni JF Jr , Freedman ND , Fridley BL , Fuchs CS , Gago-Dominguez M , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Garcia-Closas R , Gastier-Foster JM , Gaziano JM , Gerhard DS , Giffen CA , Giles GG , Gillanders EM , Giovannucci EL , Goggins M , Gokgoz N , Goldstein AM , Gonzalez C , Gorlick R , Greene MH , Gross M , Grossman HB , Grubb R 3rd , Gu J , Guan P , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Hartge P , Hattinger C , Hayes RB , He Q , Helman L , Henderson BE , Henriksson R , Hoffman-Bolton J , Hohensee C , Holly EA , Hong YC , Hoover RN , Hosgood HD 3rd , Hsiao CF , Hsing AW , Hsiung CA , Hu N , Hu W , Hu Z , Huang MS , Hunter DJ , Inskip PD , Ito H , Jacobs EJ , Jacobs KB , Jenab M , Ji BT , Johansen C , Johansson M , Johnson A , Kaaks R , Kamat AM , Kamineni A , Karagas M , Khanna C , Khaw KT , Kim C , Kim IS , Kim YH , Kim YC , Kim YT , Kang CH , Jung YJ , Kitahara CM , Klein AP , Klein R , Kogevinas M , Koh WP , Kohno T , Kolonel LN , Kooperberg C , Kratz CP , Krogh V , Kunitoh H , Kurtz RC , Kurucu N , Lan Q , Lathrop M , Lau CC , Lecanda F , Lee KM , Lee MP , Le Marchand L , Lerner SP , Li D , Liao LM , Lim WY , Lin D , Lin J , Lindstrom S , Linet MS , Lissowska J , Liu J , Ljungberg B , Lloreta J , Lu D , Ma J , Malats N , Mannisto S , Marina N , Mastrangelo G , Matsuo K , McGlynn KA , McKean-Cowdin R , McNeill LH , McWilliams RR , Melin BS , Meltzer PS , Mensah JE , Miao X , Michaud DS , Mondul AM , Moore LE , Muir K , Niwa S , Olson SH , Orr N , Panico S , Park JY , Patel AV , Patino-Garcia A , Pavanello S , Peeters PH , Peplonska B , Peters U , Petersen GM , Picci P , Pike MC , Porru S , Prescott J , Pu X , Purdue MP , Qiao YL , Rajaraman P , Riboli E , Risch HA , Rodabough RJ , Rothman N , Ruder AM , Ryu JS , Sanson M , Schned A , Schumacher FR , Schwartz AG , Schwartz KL , Schwenn M , Scotlandi K , Seow A , Serra C , Serra M , Sesso HD , Severi G , Shen H , Shen M , Shete S , Shiraishi K , Shu XO , Siddiq A , Sierrasesumaga L , Sierri S , Sihoe AD , Silverman DT , Simon M , Southey MC , Spector L , Spitz M , Stampfer M , Stattin P , Stern MC , Stevens VL , Stolzenberg-Solomon RZ , Stram DO , Strom SS , Su WC , Sund M , Sung SW , Swerdlow A , Tan W , Tanaka H , Tang W , Tang ZZ , Tardon A , Tay E , Taylor PR , Tettey Y , Thomas DM , Tirabosco R , Tjonneland A , Tobias GS , Toro JR , Travis RC , Trichopoulos D , Troisi R , Truelove A , Tsai YH , Tucker MA , Tumino R , Van Den Berg D , Van Den Eeden SK , Vermeulen R , Vineis P , Visvanathan K , Vogel U , Wang C , Wang C , Wang J , Wang SS , Weiderpass E , Weinstein SJ , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolk A , Wolpin BM , Wong MP , Wrensch M , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xiang YB , Xu J , Yang HP , Yang PC , Yatabe Y , Ye Y , Yeboah ED , Yin Z , Ying C , Yu CJ , Yu K , Yuan JM , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Mirabello L , Savage SA , Kraft P , Chanock SJ , Yeager M , Landi MT , Shi J , Chatterjee N , Amundadottir LT . Hum Mol Genet 2014 23 (24) 6616-33 ![]() Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. |
Preventing hepatitis B though universal vaccination: reduction of inequalities through the GAVI China project
Cui F , Liang X , Gong X , Chen Y , Wang F , Zheng H , Wu Z , Miao N , Hadler SC , Hutin YJ , Luo H , Yang W . Vaccine 2013 31 Suppl 9 J29-35 OBJECTIVE: In order to measure hepatitis B coverage and progress in equality with respect to protection against hepatitis B in poverty-affected areas funded by the Global Alliance on Vaccine and Immunization project funded in poverty-affected counties. METHODS: We reviewed routinely reported coverage data and conducted a national stratified, validation, cross-sectional survey in October 2010, according to WHO recommended sampling method. First, we stratified China into three regions (Eastern, Central and Western) based on economic criteria. Second, in each region, we selected eight counties with a probability proportional to population size. Third, in each selected county, we selected (a) 10 townships at random among the list of townships of the county. RESULTS: We visited 244 townships as part of the final evaluation (71 in the East, 86 in the Center and 87 in the West). Overall, in these 244 townships, surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 and surveyed three dose of hepatitis B vaccine coverage increased from 71% in 2002 to 93% in 2009. Overall, in the GAVI supported areas, the HepB3/DTP3 ratio increased from 57% in 2002 to 94% in 2009. CONCLUSION: Pro-poor GAVI approach was an effective way to reduce inequity among children through provision of free vaccination. When vaccine and AD syringes were provided for free, they closed the gap between Eastern and Western regions and between the rich and the poor. |
Evaluation of immunization injection safety in China, 2010: achievements, future sustainability
Wu Z , Cui F , Chen Y , Miao N , Gong X , Luo H , Wang F , Zheng H , Kane M , Hadler SC , Hutin YJ , Liang X , Yang W . Vaccine 2013 31 Suppl 9 J43-8 OBJECTIVE: The study objectives were to evaluate injection practices in China in the post GAVI project era and provide guidance for policy makers to update national standards for injection practices and further improve vaccination services. METHODS: We conducted a national stratified, cross-sectional survey in October 2010, according to WHO recommended sampling methods. First, we stratified China into three regions (Eastern, Central and Western) based on economic criteria. Second, in each region, we selected eight counties with a probability proportional to population size. Third, in each selected county, we selected (a) 10 townships at random among the list of townships of the county and (b) the one county level hospital. RESULTS: With respect to the risk to the patient, we never observed open injection equipment lying around or needles left in the septum of multi-dose vials. We never observed sterilizable injection devices syringes in any of the facilities. The proportion of facilities using sharps containers was highest in the East (85%), intermediate in the West (79%) and lowest in the Central region (56%). In 2009, auto-disable syringes and safety boxes were used in 78% and 79% facilities in GAVI supported areas of the Western region, respectively. Only one facility presented evidence of attempts to re-sterilize disposable injection equipment in the Eastern region. CONCLUSIONS: Use of AD syringe and sharps containers increased in vaccination services in China, especially in GAVI supported areas, leading to sustainable progress in terms of elimination of reuse of injection devices. However, risk to patients still existed, including persisting use of standard disposable syringes and attempts to re-use disposable devices. |
Evaluation of policies and practices to prevent mother to child transmission of hepatitis B virus in China: results from China GAVI project final evaluation
Cui F , Luo H , Wang F , Zheng H , Gong X , Chen Y , Wu Z , Miao N , Kane M , Hennessey K , Hadler SC , Hutin YJ , Liang X , Yang W . Vaccine 2013 31 Suppl 9 J36-42 BACKGROUND: Mother to Child Transmission (MTCT) has remained a leading cause of HBV infection in China, accounting for 40% of total infections. Providing hepatitis B vaccine (HepB) to all infants within 24h of birth (Timely Birth Dose, TBD), and subsequent completion of at least 3 vaccine doses is key to preventing perinatal HBV infection. In 2002, with the financial support of the Global Alliance on Vaccine and Immunization (GAVI) targeted to Western region and 223 poverty-affected counties in Central region, hepatitis B vaccine was provided for free. In 2010, we evaluated the China GAVI project in terms of its activities to prevent perinatal infections. OBJECTIVE: The objectives of the evaluation were to (1) measure achievements in the China GAVI project in terms of TBD coverage, and (2) describe practices for HBsAg screening of pregnant women and HBIG use outside the GAVI China project. METHODS: We used the methods recommended by WHO to select a cluster sample of health care facilities for the purpose of an injection safety assessment. We stratified China into three regions based on economic criteria, and selected eight counties with a probability proportional to population size in each region. In each selected county, we selected (a) 10 townships at random among the list of townships of the county and (b) the one county level hospital. In each hospital, we abstracted 2002 through 2009 records to collect information regarding birth cohorts, hospitals deliveries, vaccine management, hepatitis B vaccination delivery, HBsAg screening practices and results, and HBIG administration. In addition, in all hospitals, we abstracted records regarding the delivery of TBD. RESULTS: We visited 244 facilities in the three regions, including 24 county hospitals and 220 township hospitals. We reviewed 837,409 birth summary records, 699,249 for infants born at county or township hospitals. Hospital delivery rates increased from 58% in 2002 to 93% in 2009. Surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 (+31%). Surveyed TBD coverage among children born in hospitals increased from 73% in 2002 to 98% in 2009. Between 2002 and 2009, the proportion of pregnant women screened for HBsAg increased from 64% in 2002 to 85% in 2009. In 2009, the proportion of infants born to women screened and found to be HBsAg positive who did not receive any immunization within 24h after birth ranged from 0% to 0.7% across regions. CONCLUSIONS: Increased availability of hepatitis B vaccine, along with efforts to improve hospital deliveries, increased TBD coverage in China. This decreased perinatal HBV transmission and will reduce disease burden in the future. Screening for HBsAg to guide HBIG administration has begun, but with heterogeneous immuno-prophylaxis practices and a poor system for follow up. |
Decrease in formalin-inactivated respiratory syncytial virus (FI-RSV) enhanced disease with RSV G glycoprotein peptide immunization in BALB/c mice
Rey GU , Miao C , Caidi H , Trivedi SU , Harcourt JL , Tripp RA , Anderson LJ , Haynes LM . PLoS One 2013 8 (12) e83075 Respiratory syncytial virus (RSV) is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV) vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study. |
Effect of chemokine receptor CX3CR1 deficiency in a murine model of respiratory syncytial virus infection
Johnson CH , Miao C , Blanchard EG , Caidi H , Radu GU , Harcourt JL , Haynes LM . Comp Med 2012 62 (1) 14-20 ![]() Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory illness in infants and young children worldwide, making it a high priority for development of strategies for prevention and treatment. RSV can cause repeat infections throughout life, with serious complications in elderly and immunocompromised patients. Previous studies indicate that the RSV G protein binds through a CX3C chemokine motif to the host chemokine receptor, CX3CR1, and modulates the inflammatory immune response. In the current study, we examined the contribution of CX3CR1 to the immune response to RSV infection in mice. CX3CR1-deficient mice showed an impaired innate immune response to RSV infection, characterized by substantially decreased NK1.1(+) natural killer, CD11b(+), and RB6-8C5(+) polymorphonuclear cell trafficking to the lung and reduced IFNgamma production compared with those in wildtype control mice. Leukocytes from CX3CR1-deficient mice were poorly chemotactic toward RSV G protein and CX3CL1. These results substantiate the importance of the RSV G CX3C-CX3CR1 interaction in the innate immune response to RSV infection. |
Development of a recombinant truncated nucleocapsid protein based immunoassay for detection of antibodies against human coronavirus OC43
Blanchard EG , Miao C , Haupt TE , Anderson LJ , Haynes LM . J Virol Methods 2011 177 (1) 100-6 ![]() Human coronaviruses are one of the main causes of upper respiratory tract infections in humans. While more often responsible for mild illness, they have been associated with illnesses that require hospitalization. In this study, an assay for one of the human coronaviruses, OC43, was developed using a truncated recombinant nucleocapsid (N) protein antigen in an enzyme immunosorbent assay (ELISA) and evaluated using serum collected from HCoV-OC43-infected patients, healthy adults, and patients with other respiratory virus infections. Results showed that the diagnostic sensitivity and specificity of the assay were 90.9% (10/11) and 82.9% (39/47), respectively. To evaluate the clinical utility of the ELISA, serum samples collected from patients during an outbreak of HCoV-OC43 infection and previously identified as positive by HCoV-OC43 whole N ELISA were screened resulting in 100% diagnosis agreement between the testing methods. These results suggest that this assay offers a reliable method to detect HCoV-OC43 infection and may be a useful tool in coronavirus seroepidemiological studies. |
Safety and effectiveness of a 2009 H1N1 vaccine in Beijing
Wu J , Xu F , Lu L , Lu M , Miao L , Gao T , Ji W , Suo L , Liu D , Ma R , Yu R , Zhangzhu J , Liu W , Zeng Y , Li X , Zhang X , Pang X , Deng Y . N Engl J Med 2010 363 (25) 2416-23 BACKGROUND: After the first monovalent 2009 pandemic influenza A (H1N1) vaccine became available in September 2009, Chinese officials conducted a mass vaccination program in Beijing. We evaluated the safety and effectiveness of the vaccine. METHODS: During a 5-day period in September 2009, a total of 95,244 children and adults received the PANFLU.1 vaccine (Sinovac Biotech), a monovalent split-virion vaccine of 15 mug of hemagglutinin antigen without adjuvant. We assessed adverse events after immunization through an enhanced passive-surveillance system and through active surveillance, using diary cards and telephone interviews. Active surveillance for neurologic diseases was implemented in hospitals citywide. To assess vaccine effectiveness, we compared the rates of reported laboratory-confirmed cases of 2009 H1N1 virus infection in students who received the vaccine with the rates in those who did not receive the vaccine, starting 2 weeks after the mass vaccination. RESULTS: As of December 31, 2009, adverse events were reported by 193 vaccine recipients. Through hospital-based active surveillance, 362 cases of incident neurologic diseases were identified within 10 weeks after the mass vaccination, including 27 cases of the Guillain-Barre syndrome. None of the neurologic conditions occurred among vaccine recipients. From 245 schools, 25,037 students participated in the mass vaccination and 244,091 did not. During the period from October 9 through November 15, 2009, the incidence of confirmed cases of 2009 H1N1 virus infection per 100,000 students was 35.9 (9 of 25,037) among vaccinated students and 281.4 (687 of 244,091) among unvaccinated students. Thus, the estimated vaccine effectiveness was 87.3% (95% confidence interval, 75.4 to 93.4). CONCLUSIONS: Among 95,244 children and adults in Beijing, the PANFLU.1 vaccine had a safety profile similar to those of seasonal influenza vaccines and appeared to be effective against confirmed H1N1 virus infection in school-age children. (Funded by the Beijing Municipal Health Bureau.). |
Prophylactic treatment with a G glycoprotein monoclonal antibody reduces pulmonary inflammation in RSV challenged naive and formalin-inactivated RSV immunized BALB/c mice
Radu GU , Caidi H , Miao C , Tripp RA , Anderson LJ , Haynes LM . J Virol 2010 84 (18) 9632-6 We examined whether prophylactically administered anti-RSV G monoclonal antibody (mAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated (FI-RSV) enhanced disease in mice. mAb 131-2G administration one day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab')2 forms of mAb 131-2G mAB administered one day prior to infection in FI-RSV vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein mAb might provide prophylaxis against both primary infection and FI-RSV associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of non-live virus vaccines. |
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