bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Safety and Immunogenicity Study of a Candidate Meningococcal Disease Vaccine Based on
Neisseria lactamica
Outer Membrane Vesicles
Authors: Gorringe Andrew R. , Taylor Stephen , Brookes Charlotte , Matheson Mary , Finney Michelle , Kerr Moyra , Hudson Michael , Findlow Jamie , Borrow Ray , Andrews Nick , Kafatos George , Evans Cariad M. , Read Robert C. 
Published: June 2009

ABSTRACT

Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal
Neisseria
species, including
Neisseria lactamica
. We have previously demonstrated that outer membrane vesicles (OMVs) from
N. lactamica
provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an
N. lactamica
OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup B
Neisseria meningitidis
, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing ≥4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, this
N. lactamica
OMV vaccine is safe and induces a weak but broad humoral immune response to
N. meningitidis
.
Discriminating Foot-and-Mouth Disease Virus-Infected and Vaccinated Animals by Use of β-Galactosidase Allosteric Biosensors
Authors: Sánchez-Aparicio M. Teresa , Rosas María Flora , Ferraz Rosa Maria , Delgui Laura , Veloso Juan J. , Blanco Esther , Villaverde Antonio , Sobrino Francisco 
Published: June 2009

ABSTRACT
Recombinant β-galactosidases accommodating one or two different peptides from the foot-and-mouth disease virus (FMDV) nonstructural protein 3B per enzyme monomer showed a drastic enzymatic activity reduction, which mainly affected proteins with double insertions. Recombinant β-galactosidases were enzymatically reactivated by 3B-specific murine monoclonal and rabbit polyclonal antibodies. Interestingly, these recombinant β-galactosidases, particularly those including one copy of each of the two 3B sequences, were efficiently reactivated by sera from infected pigs. We found reaction conditions that allowed differentiation between sera of FMDV-infected pigs, cattle, and sheep and those of naïve and conventionally vaccinated animals. These FMDV infection-specific biosensors can provide an effective and versatile alternative for the serological distinction of FMDV-infected animals.
Characterization of Monoclonal Antibodies to Junin Virus Nucleocapsid Protein and Application to the Diagnosis of Hemorrhagic Fever Caused by South American Arenaviruses
Authors: Nakauchi Mina , Fukushi Shuetsu , Saijo Masayuki , Mizutani Tetsuya , Ure Agustín E. , Romanowski Victor , Kurane Ichiro , Morikawa Shigeru 
Published: June 2009

ABSTRACT
Junin virus (JUNV), Machupo virus, Guanarito virus, Sabia virus, and Chapare virus are members of New World arenavirus clade B and are the etiological agents of viral hemorrhagic fevers that occur in South America. In this study, we produced three monoclonal antibodies (MAbs) to the recombinant nucleocapsid protein of JUNV, designated C6-9, C11-12, and E4-2. The specificity of these MAbs was examined by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay, and an epitope-mapping method. Using these MAbs, we developed antigen (Ag) capture ELISA systems. We showed that by using MAb C6-9, JUNV Ag was specifically detected. On the other hand, by using MAb C11-12 or E-4-2, the Ags of all human pathogenic South American arenaviruses were detected. The combined use of these Ag capture ELISA systems in the present study may be useful for the diagnosis of acute-phase viral hemorrhagic fever due to infection by a South American arenavirus.
Age-Dependent Seroprevalence of Toscana Virus in Central Italy and Correlation with the Clinical Profile
Authors: Terrosi C. , Olivieri R. , Bianco C. , Cellesi C. , Cusi M. G. 
Published: June 2009

ABSTRACT

In order to estimate the antibody prevalence rates for Toscana virus (TOSV) among children and adults, we evaluated the seroprevalence of TOSV in a population (
n
= 2,737) living in Tuscany during the period of 1999 to 2006. The seroprevalence rate was 19.8% in adults and 5.8% in children, showing an age-dependent increase in TOSV-specific immunity. Meningitis due to TOSV infection was more frequent in adults than in children.
Leishmania
OligoC-TesT as a Simple, Rapid, and Standardized Tool for Molecular Diagnosis of Cutaneous Leishmaniasis in Peru
Authors: Espinosa Diego , Boggild Andrea K. , Deborggraeve Stijn , Laurent Thierry , Valencia Cristian , Pacheco Rosa , Miranda-Verástegui César , Llanos-Cuentas Alejandro , Leclipteux Thierry , Dujardin Jean-Claude , Büscher Philippe , Arévalo Jorge 
Published: June 2009

ABSTRACT

Molecular methods such as PCR have become attractive tools for diagnosis of cutaneous leishmaniasis (CL), both for their high sensitivity and for their specificity. However, their practical use in routine diagnosis is limited due to the infrastructural requirements and the lack of any standardization. Recently, a simplified and standardized PCR format for molecular detection of
Leishmania
was developed. The
Leishmania
OligoC-TesT is based on simple and rapid detection using a dipstick with PCR-amplified
Leishmania
DNA. In this study, we estimated the diagnostic accuracy of the
Leishmania
OligoC-TesT for 61 specimens from 44 CL-suspected patients presenting at the leishmaniasis clinic of the Instituto de Medicina Tropical Alexander von Humboldt, Peru. On the basis of parasitological detection and the leishmanin skin test (LST), patients were classified as (i) confirmed CL cases, (ii) LST-positive cases, and (iii) LST-negative cases. The sensitivities of the
Leishmania
OligoC-TesT was 74% (95% confidence interval (CI), 60.5% to 84.1%) for lesion aspirates and 92% (95% CI, 81.2% to 96.9%) for scrapings. A significantly higher sensitivity was observed with a conventional PCR targeting the kinetoplast DNA on the aspirates (94%) (
P
= 0.001), while there was no significant difference in sensitivity for the lesion scrapings (88%) (
P
= 0.317). In addition, the
Leishmania
OligoC-TesT was evaluated for 13 CL-suspected patients in two different peripheral health centers in the central jungle of Peru. Our findings clearly indicate the high accuracy of the
Leishmania
OligoC-TesT for lesion scrapings for simple and rapid molecular diagnosis of CL in Peru.
Emergence of European Avian Influenza Virus-Like H1N1 Swine Influenza A Viruses in China
Authors: Liu Jinhua , Bi Yuhai , Qin Kun , Fu Guanghua , Yang Jun , Peng Jinshan , Ma Guangpeng , Liu Qinfang , Pu Juan , Tian Fulin 
Published: June 2009

ABSTRACT
During swine influenza surveillance from 2007 to 2008, 10 H1N1 viruses were isolated and analyzed for their antigenic and phylogenetic properties. Our study revealed the emergence of avian-origin European H1N1 swine influenza virus in China, which highlights the necessity of swine influenza surveillance for potential pandemic preparedness.
Epidemiology and Phylogenetic Analysis of Crimean-Congo Hemorrhagic Fever Viruses in Xinjiang, China
Authors: Sun Surong , Dai Xiang , Aishan Muhetaer , Wang Xinhui , Meng Weiwei , Feng Conghui , Zhang Fuchun , Hang Changshou , Hu Zhihong , Zhang Yujiang 
Published: June 2009

ABSTRACT

In 2004 and 2005, an epidemiological survey of Crimean-Congo hemorrhagic fever virus (CCHFV) was conducted in Xinjiang, China. A total of 5,629 serum samples of human and livestock were collected and tested for the CCHFV antibody, and 17,319 ticks were collected for viral identification. Reverse passive hemagglutination inhibition assays showed that the average prevalence of CCHFV antibody was 1.7% for the humans and 12.7% for the livestock. A relatively high antibody prevalence, ranging from 19.1% to 23.4%, was found in the livestock of the northwest, southwest, and northeast parts of the Tarim Basin. When the ticks were pooled to inoculate suckling mice, followed by reverse transcription-PCR (RT-PCR) to detect CCHFV RNA, the average RT-PCR-positive rates for
Hyalomma asiaticum kozlovi
and
H. asiaticum asiaticum
were 12.9% and 2.6%, respectively. A significant correlation was found between the antibody prevalence in the livestock and the CCHFV prevalence in
H. asiaticum
of the same geographic region. No CCHFV RNA was detected in
Dermacentor nivenus
,
Rhipicephalus turanius
, or
Rhipicephalus sanguineus.
A total of 27 partial S segments of CCHFVs were sequenced and used for phylogeny analysis. All but one Chinese isolate grouped into the Asia 1 clade, which contains the strains from Xinjiang and Uzbekistan, while the other strain, Fub90009, grouped with strains from the Middle East.
Unexpectedly High Proportion of Ancestral Manu Genotype
Mycobacterium tuberculosis
Strains Cultured from Tuberculosis Patients in Egypt
Authors: Helal Zeinab H. , El-Din Ashour Mohamed Seif , Eissa Somaia A. , Abd-Elatef Ghanem , Zozio Thierry , Babapoor Sankhiros , Rastogi Nalin , Khan Mazhar I. 
Published: June 2009

ABSTRACT

Tuberculosis is one of the important public health problems in Egypt. However, limited information on the
Mycobacterium tuberculosis
genotypes circulating in Egypt is available. A total of 151
M. tuberculosis
strains were characterized by spoligotyping. The results revealed that 74.8% of
M. tuberculosis
isolates grouped into 13 different clusters, while 25.2% had unique spoligotype patterns. Comparison with an international spoligotyping database (the SITVIT2 database) showed that types SIT53 (T1 variant) and SIT54 (Manu2 variant) were the most common types between cluster groups. In addition, new shared types SIT2977, SIT2978, and SIT2979 were observed. The results identified for the first time an unusually high proportion of ancestral Manu strains of
M. tuberculosis
from patients in Egypt. The percentage of the Manu clade in this study (27.15%) was significantly higher than its overall representation of 0.4% in the SITVIT2 database. We show that in Egypt tuberculosis is caused by a predominant
M. tuberculosis
genotype belonging to the ancestral Manu lineage which could be a missing link in the split between ancestral and modern tubercle bacilli during the evolution of
M. tuberculosis
.
Comparison of Typing Results Obtained for Methicillin-Resistant
Staphylococcus aureus
Isolates with the DiversiLab System and Pulsed-Field Gel Electrophoresis
Authors: Tenover Fred C. , Gay Emily A. , Frye Stacie , Eells Samantha J. , Healy Mimi , McGowan John E. 
Published: June 2009

ABSTRACT

We compared the results of typing methicillin-resistant
Staphylococcus aureus
(MRSA) isolates using the DiversiLab system (DL) to the results obtained using pulsed-field gel electrophoresis (PFGE). One hundred five MRSA isolates of PFGE types USA100 to USA1100 and the Brazilian clone, from the Centers for Disease Control and Prevention (CDC) and Project ICARE strain collections, were typed using DL. In addition, four unique sets of MRSA isolates from purported MRSA outbreaks that had been previously typed by DL, each consisting of six isolates (where five isolates were classified as indistinguishable by DL and one was an unrelated DL type) were typed by PFGE. DL separated the 105 MRSA isolates of known USA types into 11 clusters and six unique banding patterns. DL grouped most of the USA100, USA200, and USA1100 isolates into unique clusters. Multilocus sequence type 8 isolates (i.e., USA300 and USA500) often clustered together at >95% similarity in DL dendrograms. Nevertheless, USA300 and USA500 DL patterns could be distinguished using the pattern overlay function of the DL software. Among the hospital outbreak clusters, PFGE and DL identified the same “unrelated” organism in three of four sets. However, PFGE showed more pattern diversity than did DL, suggesting that two of the sets were less likely to represent true outbreaks. In summary, DL is useful for screening MRSA isolates to rule out potential outbreaks of MRSA in hospitals, but PFGE provides better discrimination of potential outbreak strains and is more useful for confirming strain relatedness and specific USA types.
Proteomic Identification of OprL as a Seromarker for Initial Diagnosis ofPseudomonas aeruginosaInfection of Patients with Cystic Fibrosis
Authors: Rao Aparna R. , Laxova Anita , Farrell Philip M. , Barbieri Joseph T. 
Published: June 2009

ABSTRACTIdentification of new immunogenic antigens that diagnose initialPseudomonas aeruginosainfections in patients with cystic fibrosis (CF) alone or as an adjunct to microbiology is needed. In the present study, a proteomic analysis was performed to obtain a global assessment of the host immune response during the initialP. aeruginosainfection of patients with CF. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was used to identify outer membrane protein L (OprL), a non-type III secretion system (TTSS) protein, as an early immunogenic protein during the initialP. aeruginosainfection of patients with CF. Longitudinal Western blot analysis of sera from 12 of 14 patients with CF detected antibodies to OprL during the initialP. aeruginosainfection. In addition, also detected were antibodies to ExoS, ExoU, or ExoS and ExoU, the latter indicating sequentialP. aeruginosainfections during initial infections. Detection of serum reactivity to OprL, along with proteins of the TTSS, and in conjunction with microbiology may diagnose initialP. aeruginosainfections in patients with CF.
Distribution of
lag-1
Alleles and Sequence-Based Types among
Legionella pneumophila
Serogroup 1 Clinical and Environmental Isolates in the United States
Authors: Kozak Natalia A. , Benson Robert F. , Brown Ellen , Alexander Nicole T. , Taylor Thomas H. , Shelton Brian G. , Fields Barry S. 
Published: June 2009

ABSTRACT

Approximately 84% of legionellosis cases are due to
Legionella pneumophila
serogroup 1. Moreover, a majority of
L. pneumophila
serogroup 1 clinical isolates react positively with monoclonal antibody 2 (MAb2) of the international standard panel. Over 94% of the legionellosis outbreaks investigated by the Centers for Disease Control and Prevention are due to this subset of
L. pneumophila
serogroup 1. To date, there is no complete explanation for the enhanced ability of these strains to cause disease. To better characterize these organisms, we subtyped 100 clinical
L. pneumophila
serogroup 1 isolates and 50 environmental
L. pneumophila
serogroup 1 isolates from the United States by (i) reactivity with MAb2, (ii) presence of a
lag-1
gene required for the MAb2 epitope, and (iii) sequence-based typing analysis. Our results showed that the MAb2 epitope and
lag-1
gene are overrepresented in clinical
L. pneumophila
serogroup 1 isolates. MAb2 recognized 75% of clinical isolates but only 6% of environmental isolates. Similarly, 75% of clinical isolates but only 8% of environmental isolates harbored
lag-1
. We identified three distinct
lag-1
alleles, referred to as Philadelphia, Arizona, and Lens alleles, among 79 isolates carrying this gene. The Arizona allele is described for the first time in this study. We identified 59 different sequence types (STs), and 34 STs (58%) were unique to the United States. Our results support the hypothesis that a select group of STs may have an enhanced ability to cause legionellosis. Combining sequence typing and
lag-1
analysis shows that STs tend to associate with a single
lag-1
allele type, suggesting a hierarchy of virulence genotypes. Further analysis of ST and
lag-1
profiles may identify genotypes of
L. pneumophila
serogroup 1 that warrant immediate intervention.
A New World Primate Deficient in Tetherin-Mediated Restriction of Human Immunodeficiency Virus Type 1
Authors: Wong Swee Kee , Connole Michelle , Sullivan JoAnne S. , Choe Hyeryun , Carville Angela , Farzan Michael 
Published: June 2009

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) does not replicate in primary cells of New World primates. To better understand this restriction, we expressed owl monkey (
Aotus nancymaae
) CD4 and CXCR4 in the owl monkey kidney cell line, OMK. An HIV-1 variant modified to evade the owl monkey restriction factor TRIM-cyp replicated efficiently in these cells but could not replicate in primary
A. nancymaae
CD4-positive T cells. To understand this difference, we examined APOBEC3G and tetherin orthologs from OMK cells and primary
A. nancymaae
cells. We observed that OMK cells expressed substantially lower levels of APOBEC3G than did
A. nancymaae
cells.
A. nancymaae
, but not marmoset (
Callithrix jacchus
), APOBEC3G was partially downregulated by HIV-1 vif and reduced but did not abolish HIV-1 replication when stably expressed in OMK cells. The functional difference between
A. nancymaae
and marmoset APOBEC3Gs mapped to residue 128, previously shown to distinguish African green monkey from human APOBEC3G. We also characterized tetherin orthologs from OMK and
A. nancymaae
cells. The
A. nancymaae
tetherin ortholog, but not OMK tetherin, prevented HIV-1 release. Alteration of threonine 181 of OMK tetherin rescued its function and its efficient N glycosylation. All alleles of
A
otus lemurinus griseimembra
examined, but none of
A. nancymaae
or
A
otus vociferans
, encoded this nonfunctional tetherin ortholog. Our data indicate that HIV-1 replication in owl monkeys is not restricted at entry but can be limited by APOBEC3G and tetherin. Further,
A. lemurinus griseimembra
does not restrict HIV-1 replication via tetherin, a property likely useful for the study of tetherin-restricted viruses.
Human Immunodeficiency Virus Type 1 Escapes from Interleukin-2-Producing CD4
+
T-Cell Responses without High-Frequency Fixation of Mutations
Authors: Jones R. Brad , Yue Feng-Yun , Gu Xiao Xiao Jenny , Hunter Diana V. , Mujib Shariq , Gyenes Gabor , Mason Rosemarie D. , Mohamed Ruqaya , MacDonald Kelly S. , Kovacs Colin , Ostrowski Mario A. 
Published: June 2009

ABSTRACT

The presence of interleukin-2 (IL-2)-producing human immunodeficiency virus type 1 (HIV-1)-specific CD4
+
T-cell responses has been associated with the immunological control of HIV-1 replication; however, the causal relationship between these factors remains unclear. Here we show that IL-2-producing HIV-1-specific CD4
+
T cells can be cloned from acutely HIV-1-infected individuals. Despite the early presence of these cells, each of the individuals in the present study exhibited progressive disease, with one individual showing rapid progression. In this rapid progressor, three IL-2-producing HIV-1 Gag-specific CD4
+
T-cell responses were identified and mapped to the following optimal epitopes: HIVWASRELER, REPRGSDIAGT, and FRDYVDRFYKT. Responses to these epitopes in peripheral blood mononuclear cells were monitored longitudinally to >1 year postinfection, and contemporaneous circulating plasma viruses were sequenced. A variant of the FRDYVDRFYKT epitope sequence, FRDYVDQFYKT, was observed in 1/21 plasma viruses sequenced at 5 months postinfection and 1/10 viruses at 7 months postinfection. This variant failed to stimulate the corresponding CD4
+
T-cell clone and thus constitutes an escape mutant. Responses to each of the three Gag epitopes were rapidly lost, and this loss was accompanied by a loss of antigen-specific cells in the periphery as measured by using an FRDYVDRFYKT-presenting major histocompatibility complex class II tetramer. Highly active antiretroviral therapy was associated with the reemergence of FRDYVDRFYKT-specific cells by tetramer. Thus, our data support that IL-2-producing HIV-1-specific CD4
+
T-cell responses can exert immune pressure during early HIV-1 infection but that the inability of these responses to enforce enduring control of viral replication is related to the deletion and/or dysfunction of HIV-1-specific CD4
+
T cells rather than to the fixation of escape mutations at high frequencies.
Bluetongue Virus VP6 Acts Early in the Replication Cycle and Can Form the Basis of Chimeric Virus Formation
Authors: Matsuo Eiko , Roy Polly 
Published: June 2009

ABSTRACTA minor core protein, VP6, of bluetongue virus (BTV) possesses nucleoside triphosphatase, RNA binding, and helicase activities. Although the enzymatic functions of VP6 have been documented in vitro using purified protein, its definitive role in BTV replication remains unclear. In this study, using a recently developed T7 transcript-based reverse genetics system for BTV, we examined the importance of VP6 in virus replication. We show that VP6 is active early in replication, consistent with a role as part of the transcriptase or packaging complex, and that its action can be provided intransby a newly developed complementary cell line. Furthermore, the genomic segment encoding VP6 was mutated to reveal thecis-acting sequences required for replication or packaging, which subsequently enabled the construction of a chimeric BTV expressing enhanced green fluorescent protein. These data confirm that one of the 10 genome segments of BTV can be replaced with a chimeric RNA containing the essential packaging and replication signals of BTV and the coding sequence of a foreign gene.
A Novel Genotype H9N2 Influenza Virus Possessing Human H5N1 Internal Genomes Has Been Circulating in Poultry in Eastern China since 1998
Authors: Zhang Pinghu , Tang Yinghua , Liu Xiaowen , Liu Wenbo , Zhang Xiaorong , Liu Hongqi , Peng Daxin , Gao Song , Wu Yantao , Zhang Luyong , Lu Shan , Liu Xiufan 
Published: June 2009

ABSTRACT
Many novel reassortant influenza viruses of the H9N2 genotype have emerged in aquatic birds in southern China since their initial isolation in this region in 1994. However, the genesis and evolution of H9N2 viruses in poultry in eastern China have not been investigated systematically. In the current study, H9N2 influenza viruses isolated from poultry in eastern China during the past 10 years were characterized genetically and antigenically. Phylogenetic analysis revealed that these H9N2 viruses have undergone extensive reassortment to generate multiple novel genotypes, including four genotypes (J, F, K, and L) that have never been recognized before. The major H9N2 influenza viruses represented by A/Chicken/Beijing/1/1994 (Ck/BJ/1/94)-like viruses circulating in poultry in eastern China before 1998 have been gradually replaced by A/Chicken/Shanghai/F/1998 (Ck/SH/F/98)-like viruses, which have a genotype different from that of viruses isolated in southern China. The similarity of the internal genes of these H9N2 viruses to those of the H5N1 influenza viruses isolated from 2001 onwards suggests that the Ck/SH/F/98-like virus may have been the donor of internal genes of human and poultry H5N1 influenza viruses circulating in Eurasia. Experimental studies showed that some of these H9N2 viruses could be efficiently transmitted by the respiratory tract in chicken flocks. Our study provides new insight into the genesis and evolution of H9N2 influenza viruses and supports the notion that some of these viruses may have been the donors of internal genes found in H5N1 viruses.