bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Immunogenicity and Safety of a Conventional Influenza Vaccine in Patients with Type 2 Diabetes
Authors: Seo Yu Bin , Baek Ji Hyeon , Lee Jacob , Song Joon Young , Lee Jin Soo , Cheong Hee Jin , Kim Woo Joo 
Published: September 2015

ABSTRACT

No previous studies have assessed the persistence of immune responses in individuals with diabetes. We conducted this study to evaluate the long-term immunogenicity and safety of an influenza vaccine in type 2 diabetic subjects compared with nondiabetic controls. A randomized and controlled study was conducted at two university hospitals during the 2012-2013 influenza season. The study vaccine was a standard-dose trivalent subunit inactivated intramuscular vaccine. Serum hemagglutination-inhibiting (HI) antibodies were measured at the time of vaccination and 1 month and 6 months after vaccination. Local and systemic reactions were recorded for 7 days. A total of 105 diabetic patients and 108 controls were included in the analysis. One month after vaccination, both the diabetic and nondiabetic groups satisfied all of the criteria of the Committee for Medical Products for Human Use (CHMP), and the immunogenicity profiles were statistically similar between the two groups. Although the vaccine was well tolerated, and all adverse reactions were mild to moderate, there was a tendency toward a reduced incidence of local reactions in the diabetic group. All values in the long-term immunogenicity profiles were statistically similar between the two groups, except for the seroprotection rate for the A/H1N1 influenza virus strain, which was significantly lower in the elderly diabetic group than that in the elderly nondiabetic group. However, in multivariate analysis, long-term immunogenicity was associated with age and prevaccination titer, regardless of diabetes status. (This study has been registered at CRIS [
https://cris.nih.go.kr/cris/en/
] under registration no. KCT0001423.)
Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease
Authors: Weiner Zachary P. , Crew Rebecca M. , Brandt Kevin S. , Ullmann Amy J. , Schriefer Martin E. , Molins Claudia R. , Gilmore Robert D. 
Published: September 2015

ABSTRACT

Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of
Borrelia burgdorferi
proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional
in vivo
-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing.
Human Memory CD4
+
T Cell Immune Responses against Giardia lamblia
Authors: Saghaug Christina Skår , Sørnes Steinar , Peirasmaki Dimitra , Svärd Staffan , Langeland Nina , Hanevik Kurt 
Published: September 2015

ABSTRACT

The intestinal protozoan parasite
Giardia lamblia
may cause severe prolonged diarrheal disease or pass unnoticed as an asymptomatic infection. T cells seem to play an important role in the immune response to
Giardia
infection, and memory responses may last years. Recently, T
H
17 responses have been found in three animal studies of
Giardia
infection. The aim of this study was to characterize the human CD4
+
T cell responses to
Giardia
. Peripheral blood mononuclear cells (PBMCs) were obtained from 21 returning travelers with recent or ongoing giardiasis and 12 low-risk healthy controls and stimulated
in vitro
with
Giardia lamblia
proteins. Production of tumor necrosis factor alpha (TNF-α), gamma interferon, interleukin-17A (IL-17A), IL-10, and IL-4 was measured in CD4
+
effector memory (EM) T cells after 24 h by flow cytometry. After 6 days of culture, activation and proliferation were measured by flow cytometry, while an array of inflammatory cytokine levels in supernatants were measured with multiplex assays. We found the number of IL-17A-producing CD4
+
EM T cells, as well as that of cells simultaneously producing both IL-17A and TNF-α, to be significantly elevated in the
Giardia
-exposed individuals after 24 h of antigen stimulation. In supernatants of PBMCs stimulated with
Giardia
antigens for 6 days, we found inflammation-associated cytokines, including 1L-17A, as well as CD4
+
T cell activation and proliferation, to be significantly elevated in the
Giardia
-exposed individuals. We conclude that symptomatic
Giardia
infection in humans induces a CD4
+
EM T cell response of which IL-17A production seems to be an important component.
Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
Authors: Maxfield Lori F. , Abbink Peter , Stephenson Kathryn E. , Borducchi Erica N. , Ng'ang'a David , Kirilova Marinela M. , Paulino Noelix , Boyd Michael , Shabram Paul , Ruan Qian , Patel Mayank , Barouch Dan H. 
Published: September 2015

ABSTRACT

Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26
in vitro
. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors.
Detection of Polyclonality among Clinical Isolates from Prosthetic Joint Infections
Authors: De-la-Fuente Marta , Martinez-Perez Marta , Gonzalez-Pallares Iris , Esteban Jaime 
Published: September 2015

ABSTRACT
Prosthetic joint infection (PJI) is an increasingly important health concern in the Western world due to the rising number of joint arthroplasties. Although most infections are considered to be monomicrobial, the introduction of sonication procedures has led to an increase in the detection of polymicrobial infections. To date, no published studies have investigated the presence of different clones of the same species in the infected patient. The objective of this study was to analyze whether the phenomenon of polyclonality, or the appearance of different clones in the same sample, occurs in PJI. Bacteria isolated by sonication of the retrieved implant from patients with theoretically monomicrobial PJI were included in the study. Two techniques (random amplified polymorphic DNA [RAPD] and matrix-assisted laser desorption ionization–time of flight [MALDI-TOF] mass spectrometry) were used to determine the presence of several clones in the same sample. Results were analyzed to determine bacterial species and infection type (acute versus chronic). RAPD showed a predominance of polyclonal cases (16 of 19). However, when performing the analysis with MALDI-TOF, all cases were shown to be polyclonal. We were unable to establish any relationship between the two methodologies. Polyclonality is a common phenomenon in acute and chronic PJI. Further studies are needed to establish the potential implications of this phenomenon on patient outcomes.
Direct Repeat Unit (
dru
) Typing of Methicillin-Resistant Staphylococcus pseudintermedius from Dogs and Cats
Authors: Kadlec Kristina , Schwarz Stefan , Goering Richard V. , Weese J. Scott 
Published: September 2015

ABSTRACT

Methicillin-resistant
Staphylococcus pseudintermedius
(MRSP) has emerged in a remarkable manner as an important problem in dogs and cats. However, limited molecular epidemiological information is available. The aims of this study were to apply direct repeat unit (
dru
) typing in a large collection of well-characterized MRSP isolates and to use
dru
typing to analyze a collection of previously uncharacterized MRSP isolates. Two collections of MRSP isolates from dogs and cats were included in this study. The first collection comprised 115 well-characterized MRSP isolates from North America and Europe. The data for these isolates included multilocus sequence typing (MLST) and staphylococcal protein A gene (
spa)
typing results as well as SmaI macrorestriction patterns after pulsed-field gel electrophoresis (PFGE). The second collection was a convenience sample of 360 isolates from North America. The
dru
region was amplified by PCR, sequenced, and analyzed. For the first collection, the discriminatory indices of the typing methods were calculated. All isolates were successfully
dru
typed. The discriminatory power for
dru
typing (
D
= 0.423) was comparable to that of
spa
typing (
D
= 0.445) and of MLST (
D
= 0.417) in the first collection. Occasionally,
dru
typing was able to further discriminate between isolates that shared the same
spa
type. Among all 475 isolates, 26 different
dru
types were identified, with 2 predominant types (dt9a and dt11a) among 349 (73.4%) isolates. The results of this study underline that
dru
typing is a useful tool for MRSP typing, being an objective, standardized, sequence-based method that is relatively cost-efficient and easy to perform.
Complete Deletion of the Fucose Operon in Haemophilus influenzae Is Associated with a Cluster in Multilocus Sequence Analysis-Based Phylogenetic Group II Related to Haemophilus haemolyticus: Implications for Identification and Typing
Authors: de Gier Camilla , Kirkham Lea-Ann S. , Nørskov-Lauritsen Niels 
Published: September 2015

ABSTRACTNonhemolytic variants ofHaemophilus haemolyticusare difficult to differentiate fromHaemophilus influenzaedespite a wide difference in pathogenic potential. A previous investigation characterized a challenging set of 60 clinical strains using multiple PCRs for marker genes and described strains that could not be unequivocally identified as either species. We have analyzed the same set of strains by multilocus sequence analysis (MLSA) and near-full-length 16S rRNA gene sequencing. MLSA unambiguously allocated all study strains to either of the two species, while identification by 16S rRNA sequence was inconclusive for three strains. Notably, the two methods yielded conflicting identifications for two strains. Most of the “fuzzy species” strains were identified asH. influenzaethat had undergone complete deletion of the fucose operon. Such strains, which are untypeable by theH. influenzaemultilocus sequence type (MLST) scheme, have sporadically been reported and predominantly belong to a single branch ofH. influenzaeMLSA phylogenetic group II. We also found evidence of interspecies recombination betweenH. influenzaeandH. haemolyticuswithin the 16S rRNA genes. Establishing an accurate method for rapid and inexpensive identification ofH. influenzaeis important for disease surveillance and treatment.
Diagnostic Accuracy of Seven Commercial Assays for Rapid Detection of Group A Rotavirus Antigens
Authors: Kaplon Jérôme , Fremy Céline , Pillet Sylvie , Mendes Martins Lucile , Ambert-Balay Katia , Aho Serge L. , Pothier Pierre 
Published: September 2015

ABSTRACT
Seven commercial immunochromatographic assays intended for the detection of group A rotavirus antigens in human stool samples were evaluated. These assays showed similar levels of diagnostic accuracy and were suitable for the detection of rotavirus in patients with acute gastroenteritis but missed some asymptomatic rotavirus shedding identified by real-time reverse transcription-PCR.
Successful Treatment of Peritoneal Dialysis Catheter-Related Polymicrobial Peritonitis Involving Clostridium difficile
Authors: Bharti Sheena , Malhotra Prashant , Juretschko Stefan 
Published: September 2015

ABSTRACT

Clostridium difficile
is one of the most common nosocomial pathogens and the cause of pseudomembranous colitis in cases of prior antimicrobial exposure. Extraintestinal manifestations of
C. difficile
are uncommon and rarely reported. We report the first successfully treated case of catheter-related
C. difficile
peritonitis in a patient undergoing peritoneal dialysis.
Rapid Detection of Subtype H10N8 Influenza Virus by One-Step Reverse Transcription–Loop-Mediated Isothermal Amplification Methods
Authors: Bao Hongmei , Feng Xiaoxiao , Ma Yong , Shi Jianzhong , Zhao Yuhui , Gu Linlin , Wang Xiurong , Chen Hualan 
Published: September 2015

ABSTRACT
We developed hemagglutinin- and neuraminidase-specific one-step reverse transcription–loop-mediated isothermal amplification assays for detecting the H10N8 virus. The detection limit of the assays was 10 copies of H10N8 virus, and the assays did not amplify nonspecific RNA. The assays can detect H10N8 virus from chicken samples with high sensitivity and specificity, and they can serve as an effective tool for detecting and monitoring H10N8 virus in live poultry markets.
Commentary: The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug-Resistant Tuberculosis
Authors: Somoskovi Akos , Salfinger Max 
Published: September 2015

ABSTRACT

To realize the most benefit from multidrug-resistant tuberculosis (MDR-TB) screening, all nucleic acid amplification test (NAAT)-positive respiratory specimens should be universally tested. Once an MDR-TB diagnosis is established, additional testing is warranted to provide details about the detected mutations. The lab-on-chip technology described by A. M. Cabibbe et al. (J Clin Microbiol 53:3876–3880, 2015,
http://dx.doi.org/10.1128/JCM.01824-15
) potentially provides this much needed information.
Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia
Authors: Betancourt Dillon , Ramos Juan Carlos , Barber Glen N. 
Published: September 2015

ABSTRACT

Adult T cell leukemia/lymphoma (ATL) is an aggressive cancer of CD4/CD25
+
T lymphocytes, the etiological agent of which is human T-cell lymphotropic virus type 1 (HTLV-1). ATL is highly refractory to current therapies, making the development of new treatments a high priority. Oncolytic viruses such as vesicular stomatitis virus (VSV) are being considered as anticancer agents since they readily infect transformed cells compared to normal cells, the former appearing to exhibit defective innate immune responses. Here, we have evaluated the efficacy and safety of a recombinant VSV that has been retargeted to specifically infect and replicate in transformed CD4
+
cells. This was achieved by replacing the single VSV glycoprotein (G) with human immunodeficiency virus type 1 (HIV-1) gp160 to create a hybrid fusion protein, gp160G. The resultant virus, VSV-gp160G, was found to only target cells expressing CD4 and retained robust oncolytic activity against HTLV-1 actuated ATL cells. VSV-gp160G was further noted to be highly attenuated and did not replicate efficiently in or induce significant cell death of primary CD4
+
T cells. Accordingly, VSV-gp160G did not elicit any evidence of neurotoxicity even in severely immunocompromised animals such as NOD/Shi-scid, IL-2Rγ-c-null (NSG) mice. Importantly, VSV-gp160G effectively exerted potent oncolytic activity in patient-derived ATL transplanted into NSG mice and facilitated a significant survival benefit. Our data indicate that VSV-gp160G exerts potent oncolytic efficacy against CD4
+
malignant cells and either alone or in conjunction with established therapies may provide an effective treatment in patients displaying ATL.

IMPORTANCE
Adult T cell leukemia (ATL) is a serious form of cancer with a high mortality rate. HTLV-1 infection is the etiological agent of ATL and, unfortunately, most patients succumb to the disease within a few years. Current treatment options have failed to significantly improve survival rate. In this study, we developed a recombinant strain of vesicular stomatitis virus (VSV) that specifically targets transformed CD4
+
T cells through replacement of the G protein of VSV with a hybrid fusion protein, combining domains from gp160 of HIV-1 and VSV-G. This modification eliminated the normally broad tropism of VSV and restricted infection to primarily the transformed CD4
+
cell population. This effect greatly reduced neurotoxic risk associated with VSV infection while still allowing VSV to effectively target ATL cells.
RIG-I Signaling Is Essential for Influenza B Virus-Induced Rapid Interferon Gene Expression
Authors: Mäkelä Sanna M. , Österlund Pamela , Westenius Veera , Latvala Sinikka , Diamond Michael S. , Gale Michael , Julkunen Ilkka 
Published: September 2015

ABSTRACT
Influenza B virus causes annual epidemics and, along with influenza A virus, accounts for substantial disease and economic burden throughout the world. Influenza B virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza A virus. Influenza B virus has been less studied than influenza A virus, and thus, a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions. Here we analyzed the early events in influenza B virus infection and interferon (IFN) gene expression in human monocyte-derived macrophages and dendritic cells. We show that influenza B virus induces IFN regulatory factor 3 (IRF3) activation and IFN-λ1 gene expression with faster kinetics than does influenza A virus, without a requirement for viral protein synthesis or replication. Influenza B virus-induced activation of IRF3 required the fusion of viral and endosomal membranes, and nuclear accumulation of IRF3 and viral NP occurred concurrently. In comparison, immediate early IRF3 activation was not observed in influenza A virus-infected macrophages. Experiments with RIG-I-, MDA5-, and RIG-I/MDA5-deficient mouse fibroblasts showed that RIG-I is the critical pattern recognition receptor needed for the influenza B virus-induced activation of IRF3. Our results show that innate immune mechanisms are activated immediately after influenza B virus entry through the endocytic pathway, whereas influenza A virus avoids early IRF3 activation and IFN gene induction.

IMPORTANCE
Recently, a great deal of interest has been paid to identifying the ligands for RIG-I under conditions of natural infection, as many previous studies have been based on transfection of cells with different types of viral or synthetic RNA structures. We shed light on this question by analyzing the earliest step in innate immune recognition of influenza B virus by human macrophages. We show that influenza B virus induces IRF3 activation, leading to IFN gene expression after viral RNPs (vRNPs) are released into the cytosol and are recognized by RIG-I receptor, meaning that the incoming influenza B virus is already able to activate IFN gene expression. In contrast, influenza A (H3N2) virus failed to activate IRF3 at very early times of infection, suggesting that there are differences in innate immune recognition between influenza A and B viruses.
Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model
Authors: Sreenivasan Chithra , Thomas Milton , Sheng Zizhang , Hause Ben M. , Collin Emily A. , Knudsen David E. B. , Pillatzki Angela , Nelson Eric , Wang Dan , Kaushik Radhey S. , Li Feng 
Published: September 2015

ABSTRACT
Influenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus.

IMPORTANCE
Influenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts of guinea pigs, similarly to virus infection in its native host, demonstrates that guinea pigs would be a suitable model host to study the replication and transmission potential of bovine FLUDV.