Publisher: American Society for Microbiology   (Total: 17 journals)   [Sort by number of followers]

Showing 1 - 17 of 17 Journals sorted alphabetically
Antimicrobial Agents and Chemotherapy     Hybrid Journal   (Followers: 27, SJR: 2.291, CiteScore: 4)
Applied and Environmental Microbiology     Hybrid Journal   (Followers: 57, SJR: 1.684, CiteScore: 4)
Clinical and Vaccine Immunology     Hybrid Journal   (Followers: 10, SJR: 1.32, CiteScore: 3)
Clinical Microbiology Reviews     Hybrid Journal   (Followers: 23, SJR: 11.301, CiteScore: 23)
EcoSal Plus     Hybrid Journal   (Followers: 1)
Infection and Immunity     Hybrid Journal   (Followers: 25, SJR: 1.954, CiteScore: 3)
J. of Bacteriology     Hybrid Journal   (Followers: 27, SJR: 1.885, CiteScore: 3)
J. of Clinical Microbiology     Hybrid Journal   (Followers: 38, SJR: 2.256, CiteScore: 4)
J. of Microbiology & Biology Education     Open Access   (Followers: 7)
J. of Virology     Hybrid Journal   (Followers: 36, SJR: 2.853, CiteScore: 4)
mBio     Open Access   (Followers: 16, SJR: 4.106, CiteScore: 6)
Microbiology and Molecular Biology Reviews     Hybrid Journal   (Followers: 25, SJR: 7.524, CiteScore: 14)
Microbiology Resource Announcements     Open Access  
Microbiology Spectrum     Hybrid Journal  
Molecular and Cellular Biology     Hybrid Journal   (Followers: 23, SJR: 3.174, CiteScore: 4)
mSphere     Open Access   (Followers: 3, SJR: 2.03, CiteScore: 3)
mSystems     Open Access   (Followers: 5, SJR: 3.233, CiteScore: 5)
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Journal Cover
Clinical and Vaccine Immunology
Journal Prestige (SJR): 1.32
Citation Impact (citeScore): 3
Number of Followers: 10  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1556-6811 - ISSN (Online) 1556-679X
Published by American Society for Microbiology Homepage  [17 journals]
  • Editorial Board [Masthead]

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      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.masthead.24-12
      Issue No: Vol. 24, No. 12 (2017)
       
  • GI-19007, a Novel Saccharomyces cerevisiae-Based Therapeutic Vaccine
           against Tuberculosis [Vaccines]

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      Authors: King, T. H; Shanley, C. A, Guo, Z, Bellgrau, D, Rodell, T, Furney, S, Henao-Tamayo, M, Orme, I. M.
      Abstract: As yet, very few vaccine candidates with activity in animals against Mycobacterium tuberculosis infection have been tested as therapeutic postexposure vaccines. We recently described two pools of mycobacterial proteins with this activity, and here we describe further studies in which four of these proteins (Rv1738, Rv2032, Rv3130, and Rv3841) were generated as a fusion polypeptide and then delivered in a novel yeast-based platform (Tarmogen) which itself has immunostimulatory properties, including activation of Toll-like receptors. This platform can deliver antigens into both the class I and class II antigen presentation pathways and stimulate strong Th1 and Th17 responses. In mice this fusion vaccine, designated GI-19007, was immunogenic and elicited strong gamma interferon (IFN-) and interleukin-17 (IL-17) responses; despite this, they displayed minimal prophylactic activity in mice that were subsequently infected with a virulent clinical strain. In contrast, in a therapeutic model in the guinea pig, GI-19007 significantly reduced the lung bacterial load and reduced lung pathology, particularly in terms of secondary lesion development, while significantly improving survival in one-third of these animals. In further studies in which guinea pigs were vaccinated with BCG before challenge, therapeutic vaccination with GI-19007 initially improved survival versus that of animals given BCG alone, although this protective effect was gradually lost at around 400 days after challenge. Given its apparent ability to substantially limit bacterial dissemination within and from the lungs, GI-19007 potentially can be used to limit lung damage as well as facilitating chemotherapeutic regimens in infected individuals.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00245-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody
           after Natural Infection with Influenza A Viruses [Clinical Immunology]

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      Authors: Changsom, D; Jiang, L, Lerdsamran, H, Iamsirithaworn, S, Kitphati, R, Pooruk, P, Auewarakul, P, Puthavathana, P.
      Abstract: The kinetics, longevity, and breadth of antibodies to influenza virus neuraminidase (NA) in archival, sequential serum/plasma samples from influenza A virus (IAV) H5N1 infection survivors and from patients infected with the 2009 pandemic IAV (H1N1) virus were determined using an enzyme-linked lectin-based assay. The reverse-genetics-derived H4N1 viruses harboring a hemagglutinin (HA) segment from A/duck/Shan Tou/461/2000 (H4N9) and an NA segment derived from either IAV H5N1 clade 1, IAV H5N1 clade 2.3.4, the 2009 pandemic IAV (H1N1) (H1N1pdm), or A/Puerto Rico/8/1934 (H1N1) virus were used as the test antigens. These serum/plasma samples were also investigated by microneutralization (MN) and/or hemagglutination inhibition (HI) assays. Neuraminidase-inhibiting (NI) antibodies against N1 NA of both homologous and heterologous viruses were observed in H5N1 survivors and H1N1pdm patients. H5N1 survivors who were never exposed to H1N1pdm virus developed NI antibodies to H1N1pdm NA. Seroconversion of NI antibodies was observed in 65% of the H1N1pdm patients at day 7 after disease onset, but an increase in titer was not observed in serum samples obtained late in infection. On the other hand, an increase in seroconversion rate with the HI assay was observed in the follow-up series of sera obtained on days 7, 14, 28, and 90 after infection. The study also showed that NI antibodies are broadly reactive, while MN and HI antibodies are more strain specific.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00248-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Identification of Novel Antigens Recognized by Serum Antibodies in Bovine
           Tuberculosis [Diagnostic Laboratory Immunology]

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      Authors: Lyashchenko, K. P; Grandison, A, Keskinen, K, Sikar-Gang, A, Lambotte, P, Esfandiari, J, Ireton, G. C, Vallur, A, Reed, S. G, Jones, G, Vordermeier, H. M, Stabel, J. R, Thacker, T. C, Palmer, M. V, Waters, W. R.
      Abstract: Bovine tuberculosis (TB), caused by Mycobacterium bovis, remains an important zoonotic disease posing a serious threat to livestock and wildlife. The current TB tests relying on cell-mediated and humoral immune responses in cattle have performance limitations. To identify new serodiagnostic markers of bovine TB, we screened a panel of 101 recombinant proteins, including 10 polyepitope fusions, by a multiantigen print immunoassay (MAPIA) with well-characterized serum samples serially collected from cattle with experimental or naturally acquired M. bovis infection. A novel set of 12 seroreactive antigens was established. Evaluation of selected proteins in the dual-path platform (DPP) assay showed that the highest diagnostic accuracy (~95%) was achieved with a cocktail of five best-performing antigens, thus demonstrating the potential for development of an improved and more practical serodiagnostic test for bovine TB.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00259-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Development of an Extended-Specificity Multiplex Immunoassay for Detection
           of Streptococcus pneumoniae Serotype-Specific Antigen in Urine by Use of
           Human Monoclonal Antibodies [Diagnostic Laboratory Immunology]

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      Authors: Eletu, S. D; Sheppard, C. L, Thomas, E, Smith, K, Daniel, P, Litt, D. J, Lim, W. S, Fry, N. K.
      Abstract: Current pneumococcal vaccines cover the 10 to 23 most common serotypes of the 92 presently described. However, with the increased usage of pneumococcal-serotype-based vaccines, the risk of serotype replacement and an increase in disease caused by nonvaccine serotypes remains. Serotype surveillance of pneumococcal infections relies heavily on culture techniques, which are known to be insensitive, particularly in cases of noninvasive disease. Pneumococcal-serotype-specific urine assays offer an alternative method of serotyping for both invasive and noninvasive disease. However, the assays described previously cover mainly conjugate vaccine serotypes, give little information about circulating nonvaccine serotypes, and are currently available only in one or two specialist laboratories. Our laboratory has developed a Luminex-based extended-range antigen capture assay to detect pneumococcal-serotype-specific antigens in urine samples. The assay targets 24 distinct serotypes/serogroups plus the cell wall polysaccharide (CWP) and some cross-reactive serotypes. We report that the assay is capable of detecting all the targeted serotypes and the CWP at 0.1 ng/ml, while some serotypes are detected at concentrations as low as 0.3 pg/ml. The analytical serotype specificity was determined to be 98.4% using a panel of polysaccharide-negative urine specimens spiked with nonpneumococcal bacterial antigens. We also report clinical sensitivities of 96.2% and specificities of 89.9% established using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease. This assay can be extended for testing other clinical samples and has the potential to greatly improve serotype-specific surveillance in the many cases of pneumococcal disease in which a culture is never obtained.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00262-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the
           Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a
           High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with
           Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator
           [Vaccines]

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      Authors: Sow, S. O; Tapia, M. D, Chen, W. H, Haidara, F. C, Kotloff, K. L, Pasetti, M. F, Blackwelder, W. C, Traore, A, Tamboura, B, Doumbia, M, Diallo, F, Coulibaly, F, Onwuchekwa, U, Kodio, M, Tennant, S. M, Reymann, M, Lam, D. F, Gurwith, M, Lock, M, Yonker, T, Smith, J, Simon, J. K, Levine, M. M.
      Abstract: Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 x 108 CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 x 109 CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 x 108-CFU standard dose (n = 50) or a ≥2 x 109-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ~2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.)
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00265-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Progress toward Development of a Vaccine against Congenital
           Cytomegalovirus Infection [Minireviews]

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      Authors: Schleiss, M. R; Permar, S. R, Plotkin, S. A.
      Abstract: A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00268-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Recent Approaches To Optimize Laboratory Assessment of Antinuclear
           Antibodies [Minireviews]

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      Authors: Tebo; A. E.
      Abstract: The presence of antinuclear antibodies (ANAs) is a hallmark of a number of systemic autoimmune rheumatic diseases, and testing is usually performed as part of the initial diagnostic workup when suspicion of an underlying autoimmune disorder is high. The indirect immunofluorescence antibody (IFA) technique is the preferred method for detecting ANAs, as it demonstrates binding to specific intracellular structures within the cells, resulting in a number of staining patterns that are usually categorized based on the cellular components recognized and the degree of binding, as reflected by the fluorescence intensity or titer. As a screening tool, the ANA patterns can guide confirmatory testing useful in elucidating a specific clinical diagnosis or prognosis. However, routine use of ANA IFA testing as a global screening test is hampered by its labor-intensiveness, subjectivity, and limited diagnostic specificity, among other factors. This review focuses on current efforts to standardize the nomenclature of ANA patterns and on alternative methods for ANA determination, as well as on recent advances in image-based computer algorithms to automate IFA testing in clinical laboratories.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00270-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine
           Elicits a Balanced Humoral and Cellular Response and Protects Young and
           Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent
           Humoral Response [Vaccines]

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      Authors: Hodgins, B; Yam, K. K, Winter, K, Pillet, S, Landry, N, Ward, B. J.
      Abstract: Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice received a single 3-μg dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00273-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Acknowledgment of Ad Hoc Reviewers [Editorial]

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      Authors: Pasetti; M. F.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00274-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Protein Structure Facilitates High-Resolution Immunological Mapping
           [Commentary]

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      Authors: Zuverink, M; Barbieri, J. T.
      Abstract: Select agents (SA) pose unique challenges for licensing vaccines and therapies. In the case of toxin-mediated diseases, HHS assigns guidelines for SA use, oversees vaccine and therapy development, and approves animal models and approaches to identify mechanisms for toxin neutralization. In this commentary, we discuss next-generation vaccines and therapies against ricin toxin and botulinum toxin, which are regulated SA toxins that utilize structure-based approaches for countermeasures to guide rapid response to future biothreats.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00275-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • The Legacy of CVI [Editorial]

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      Authors: Pasetti, M. F; Douglas, S. D, Plaeger, S. F.
      Abstract: Clinical and Vaccine Immunology (CVI) will merge with the American Society for Microbiology (ASM) open-access journal mSphere in January 2018. We commemorate this transition by exploring the history of CVI and that of its predecessor, Clinical and Diagnostic Laboratory Immunology (CDLI), and by acknowledging their contributors. Research on vaccines, clinical immunology, and clinical diagnostic immunology published through mSphere will be available without restrictions to an ever-larger audience, which will expedite progress in the field. ASM remains committed to supporting its members and the research community by facilitating the dissemination of scientific knowledge in these important areas.
      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00276-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Article of Significant Interest Selected from This Issue by the Editors
           [Spotlight]

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      PubDate: 2017-12-05T08:00:30-08:00
      DOI: 10.1128/CVI.00278-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Development and Qualification of an Opsonophagocytic Killing Assay To
           Assess Immunogenicity of a Bioconjugated Escherichia coli Vaccine
           [Vaccines]

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      Authors: Abbanat, D; Davies, T. A, Amsler, K, He, W, Fae, K, Janssen, S, Poolman, J. T, van den Dobbelsteen, G. P. J. M.
      Abstract: The global burden of disease caused by extraintestinal pathogenic Escherichia coli (ExPEC) is increasing as the prevalence of multidrug-resistant strains rises. A multivalent ExPEC O-antigen bioconjugate vaccine could have a substantial impact in preventing bacteremia and urinary tract infections. Development of an ExPEC vaccine requires a readout to assess the functionality of antibodies. We developed an opsonophagocytic killing assay (OPA) for four ExPEC serotypes (serotypes O1A, O2, O6A, and O25B) based on methods established for pneumococcal conjugate vaccines. The performance of the assay was assessed with human serum by computing the precision, linearity, trueness, total error, working range, and specificity. Serotypes O1A and O6A met the acceptance criteria for precision (coefficient of variation for repeatability and intermediate precision, ≤50%), linearity (90% confidence interval of the slope of each strain, 0.80, 1.25), trueness (relative bias range, –30% to 30%), and total error (total error range, –65% to 183%) at five serum concentrations and serotypes O2 and O25B met the acceptance criteria at four concentrations (the lowest concentration for serotypes O2 and O25B did not meet the system suitability test of maximum killing of ≥85% of E. coli cells). All serotypes met the acceptance criteria for specificity (opsonization index value reductions of ≤20% for heterologous serum preadsorption and ≥70% for homologous serum preadsorption). The assay working range was defined on the basis of the lowest and highest concentrations at which the assay jointly fulfilled the target acceptance criteria for linearity, precision, and accuracy. An OPA suitable for multiple E. coli serotypes has been developed, qualified, and used to assess the immunogenicity of a 4-valent E. coli bioconjugate vaccine (ExPEC4V) administered to humans.
      PubDate: 2017-12-05T08:00:29-08:00
      DOI: 10.1128/CVI.00123-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in
           the Live Salmonella Oral Vaccine Vector Ty21a [Vaccines]

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      Authors: Dharmasena, M. N; Osorio, M, Takeda, K, Stibitz, S, Kopecko, D. J.
      Abstract: We have been exploring the use of the live attenuated Salmonella enterica serovar Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression and delivery of multiple foreign antigens, including Shigella O-antigens. In this study, we separately cloned genes necessary for the biosynthesis of the Shigella flexneri serotype 2a and 3a O-antigens, which have been shown to provide broad cross-protection to multiple disease-predominant S. flexneri serotypes. The cloned S. flexneri 2a rfb operon, along with bgt and gtrII, contained on the SfII bacteriophage, was sufficient in Ty21a to express the heterologous S. flexneri 2a O-antigen containing the 3,4 antigenic determinants. Further, this rfb operon, along with gtrA, gtrB, and gtrX contained on the Sfx bacteriophage and oac contained on the Sf6 bacteriophage, was sufficient to express S. flexneri 3a O-antigen containing the 6, 7, and 8 antigenic determinants. Ty21a, with these plasmid-carried or chromosomally inserted genes, demonstrated simultaneous and stable expression of homologous S. Typhi O-antigen plus the heterologous S. flexneri O-antigen. Candidate Ty21a vaccine strains expressing heterologous S. flexneri 2a or 3a lipopolysaccharide (LPS) elicited significant serum antibody responses against both homologous S. Typhi and heterologous Shigella LPS and protected mice against virulent S. flexneri 2a or 3a challenges. These new S. flexneri 2a and 3a O-antigen-expressing Ty21a vaccine strains, together with our previously constructed Ty21a strains expressing Shigella sonnei or Shigella dysenteriae 1 O-antigens, have the potential to be used together for simultaneous protection against the predominant causes of shigellosis worldwide as well as against typhoid fever.
      PubDate: 2017-12-05T08:00:29-08:00
      DOI: 10.1128/CVI.00181-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • Development of a High-Throughput Respiratory Syncytial Virus Fluorescent
           Focus-Based Microneutralization Assay [Diagnostic Laboratory Immunology]

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      Authors: Shambaugh, C; Azshirvani, S, Yu, L, Pache, J, Lambert, S. L, Zuo, F, Esser, M. T.
      Abstract: Neutralizing antibodies specific for respiratory syncytial virus (RSV) represent a major protective mechanism against RSV infection, as demonstrated by the efficacy of the immune-prophylactic monoclonal antibody palivizumab in preventing RSV-associated lower respiratory tract infections in premature infants. Accordingly, the RSV neutralization assay has become a key functional method to assess the neutralizing activity of serum antibodies in preclinical animal models, epidemiology studies, and clinical trials. In this study, we qualified a 24-h, fluorescent focus-based microneutralization (RSVA FFA-MN) method that requires no medium exchange or pre- or postinfection processing to detect green fluorescent protein-expressing RSV strain A2 (RSVA-GFP)-infected cells, using a high-content imaging system for automated image acquisition and focus enumeration. The RSVA FFA-MN method was shown to be sensitive, with a limit of detection (LOD) and limit of quantitation (LOQ) of 1:10, or 3.32 log2; linear over a range of 4.27 to 9.65 log2 50% inhibitory concentration (IC50); and precise, with intra- and interassay coefficients of variation of
      PubDate: 2017-12-05T08:00:29-08:00
      DOI: 10.1128/CVI.00225-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • High-Resolution Epitope Positioning of a Large Collection of Neutralizing
           and Nonneutralizing Single-Domain Antibodies on the Enzymatic and Binding
           Subunits of Ricin Toxin [Clinical Immunology]

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      Authors: Vance, D. J; Tremblay, J. M, Rong, Y, Angalakurthi, S. K, Volkin, D. B, Middaugh, C. R, Weis, D. D, Shoemaker, C. B, Mantis, N. J.
      Abstract: We previously produced a heavy-chain-only antibody (Ab) VH domain (VHH)-displayed phage library from two alpacas that had been immunized with ricin toxoid and nontoxic mixtures of the enzymatic ricin toxin A subunit (RTA) and binding ricin toxin B subunit (RTB) (D. J. Vance, J. M. Tremblay, N. J. Mantis, and C. B. Shoemaker, J Biol Chem 288:36538–36547, 2013, https://doi.org/10.1074/jbc.M113.519207). Initial and subsequent screens of that library by direct enzyme-linked immunosorbent assay (ELISA) yielded more than two dozen unique RTA- and RTB-specific VHHs, including 10 whose structures were subsequently solved in complex with RTA. To generate a more complete antigenic map of ricin toxin and to define the epitopes associated with toxin-neutralizing activity, we subjected the VHH-displayed phage library to additional "pannings" on both receptor-bound ricin and antibody-captured ricin. We now report the full-length DNA sequences, binding affinities, and neutralizing activities of 68 unique VHHs: 31 against RTA, 33 against RTB, and 4 against ricin holotoxin. Epitope positioning was achieved through cross-competition ELISAs performed with a panel of monoclonal antibodies (MAbs) and verified, in some instances, with hydrogen-deuterium exchange mass spectrometry. The 68 VHHs grouped into more than 20 different competition bins. The RTA-specific VHHs with strong toxin-neutralizing activities were confined to bins that overlapped two previously identified neutralizing hot spots, termed clusters I and II. The four RTB-specific VHHs with potent toxin-neutralizing activity grouped within three adjacent bins situated at the RTA-RTB interface near cluster II. These results provide important insights into epitope interrelationships on the surface of ricin and delineate regions of vulnerability that can be exploited for the purpose of vaccine and therapeutic development.
      PubDate: 2017-12-05T08:00:29-08:00
      DOI: 10.1128/CVI.00236-17
      Issue No: Vol. 24, No. 12 (2017)
       
  • High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope
           Clusters on RiVax, a Candidate Ricin Toxin Subunit Vaccine [Vaccines]

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      Authors: Toth, R. T; Angalakurthi, S. K, Van Slyke, G, Vance, D. J, Hickey, J. M, Joshi, S. B, Middaugh, C. R, Volkin, D. B, Weis, D. D, Mantis, N. J.
      Abstract: RiVax is a promising recombinant ricin toxin A subunit (RTA) vaccine antigen that has been shown to be safe and immunogenic in humans and effective at protecting rhesus macaques against lethal-dose aerosolized toxin exposure. We previously used a panel of RTA-specific monoclonal antibodies (MAbs) to demonstrate, by competition enzyme-linked immunosorbent assay (ELISA), that RiVax elicits similar serum antibody profiles in humans and macaques. However, the MAb binding sites on RiVax have yet to be defined. In this study, we employed hydrogen exchange-mass spectrometry (HX-MS) to localize the epitopes on RiVax recognized by nine toxin-neutralizing MAbs and one nonneutralizing MAb. Based on strong protection from hydrogen exchange, the nine MAbs grouped into four spatially distinct epitope clusters (namely, clusters I to IV). Cluster I MAbs protected RiVax's α-helix B (residues 94 to 107), a protruding immunodominant secondary structure element known to be a target of potent toxin-neutralizing antibodies. Cluster II consisted of two subclusters located on the "back side" (relative to the active site pocket) of RiVax. One subcluster involved α-helix A (residues 14 to 24) and α-helices F-G (residues 184 to 207); the other encompassed β-strand d (residues 62 to 69) and parts of α-helices D-E (154 to 164) and the intervening loop. Cluster III involved α-helices C and G on the front side of RiVax, while cluster IV formed a sash from the front to back of RiVax, spanning strands b, c, and d (residues 35 to 59). Having a high-resolution B cell epitope map of RiVax will enable the development and optimization of competitive serum profiling assays to examine vaccine-induced antibody responses across species.
      PubDate: 2017-12-05T08:00:29-08:00
      DOI: 10.1128/CVI.00237-17
      Issue No: Vol. 24, No. 12 (2017)
       
 
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