459 results on '"Chen, Wilbur"'
Search Results
152. Sensitivity of Teleconnection Patterns to the Sign of Their Primary Action Center
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Chen, Wilbur Y., primary and Van den Dool, Huug, additional
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- 2003
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153. Significant change of extratropical natural variability and potential predictability associated with the El Nino/Southern Oscillation
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CHEN, WILBUR Y., primary and VAN DEN DOOL, HUUG M., additional
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- 1999
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154. Present-day capabilities of numerical and statistical models for atmospheric extratropical seasonal simulation and prediction
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Anderson, Jeffrey, Dool, Huug van den, Barnston, Anthony, Chen, Wilbur, Stern, William, American journalist, and Ploshay, Jeffrey
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Climatology -- Research ,Atmospheric circulation -- Models ,Business ,Earth sciences - Abstract
A statistical model and extended ensemble integrations of two atmospheric general circulation models (GCMs) are used to simulate the extratropical atmospheric response to forcing by observed SSTs for the years 1980 through 1988. The simulations are compared to observations using the anomaly correlation and root-mean-square error of the 700-hPa height field over a region encompassing the extratropical North Pacific Ocean and most of North America. On average, the statistical model is found to produce considerably better simulations than either numerical model, even when simple statistical corrections are used to remove systematic errors from the numerical model simulations. In the mean, the simulation skill is low, but there are some individual seasons for which all three models produce simulations with good skill. An approximate upper bound to the simulation skill that could be expected from a GCM ensemble, if the model's response to SST forcing is assumed to be perfect, is computed. This perfect model predictability allows one to make some rough extrapolations about the skill that could be expected if one could greatly improve the mean response of the GCMs without significantly impacting the variance of the ensemble. These perfect model predictability skills are better than the statistical model simulations during the summer, but for the winter, present-day statistical forecasts already have skill that is as high as the upper bound for the GCMs. Simultaneous improvements to the GCM mean response and reduction in the GCM ensemble variance would be required for these GCMs to do significantly better than the statistical model in winter. This does not preclude the possibility that, as is presently the case, a statistical blend of GCM and statistical predictions could produce a simulation better than either alone. Because of the primitive state of coupled ocean-atmosphere GCMs, the vast majority of seasonal predictions currently produced by GCMs are performed using a two-tiered approach in which SSTs are first predicted and then used to force an atmospheric model; this motivates the examination of the simulation problem. However, it is straightforward to use the statistical model to produce true forecasts by changing its predictors from simultaneous to precursor SSTs. An examination of the decrease in skill of the statistical model when changed from simulation to prediction mode is extrapolated to draw conclusions about the skill to be expected from good coupled GCM predictions.
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- 1999
155. Low-frequency variabilities for widely different basic flows
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CHEN, WILBUR Y., primary and VAN DEN DOOL, HUUG M., additional
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- 1995
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156. Forecast Skill and Low-Frequency Variability in NMC DERF90 Experiments
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Chen, Wilbur Y., primary and van den Dool, Huug M., additional
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- 1995
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157. Persistence of Antibody to Influenza A/H5N1 Vaccine Virus: Impact of AS03 Adjuvant
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Chen, Wilbur H., Jackson, Lisa A., Edwards, Kathryn M., Keitel, Wendy A., Hill, Heather, Noah, Diana L., Creech, C. Buddy, Patel, Shital M., Mangal, Brian, and Kotloff, Karen L.
- Abstract
ABSTRACTThe adjuvant AS03 is stockpiled for future formulations with new and existing vaccines for the control of pandemic influenza virus. We previously reported the immunogenicity of an A/H5N1 vaccine extemporaneously mixed with the AS03 adjuvant for 42 days following vaccination. This report extends those findings to 1 year after vaccination.
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- 2015
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158. Safety and Immunogenicity of Escalating Dosages of a Single Oral Administration of Peru-15 pCTB, a Candidate Live, Attenuated Vaccine against Enterotoxigenic Escherichia coliand Vibrio cholerae
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Chen, Wilbur H., Garza, Jose, Choquette, Monique, Hawkins, Jennifer, Hoeper, Amy, Bernstein, David I., and Cohen, Mitchell B.
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ABSTRACTEnterotoxigenic Escherichia coli(ETEC) organisms are a leading cause of infectious diarrhea in developing countries. A live, attenuated cholera strain that expresses high levels of the nontoxic B subunit of cholera toxin, which might also serve as an ETEC protective antigen, was evaluated for safety, excretion, and immunogenicity in healthy volunteers. We enrolled four inpatient dose-escalation cohorts of 15 to 16 eligible subjects to randomly (3:1) receive a single oral dose of vaccine or placebo (buffer alone), evaluating 1 ×107, 1 ×108, 1 ×109, and 1 ×1010CFU of the vaccine. The vaccine was well tolerated, although some subjects experienced moderate diarrhea. The serum Inaba vibriocidal antibody response appeared to display a dose-response relationship with increasing dosages of vaccine, plateauing at the 109-CFU dosage. The serum antitoxin (cholera toxin and heat-labile enterotoxin) antibody seroconversion rate (4-fold increase over baseline) also appeared to display a dose-response relationship. The vaccine strain was excreted in stool cultures, displaying a dose-response relationship. A single oral dose of Peru-15 pCTB at dosages up to 1 ×1010CFU was safe and immunogenic in this first-in-human trial. These encouraging data support the ongoing clinical development of this candidate combined cholera and ETEC vaccine. (This study has been registered at ClinicalTrials.gov under registration no. NCT00654108.)
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- 2014
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159. Effects of Transient Eddies on Blocking Flows: General Circulation Model Experiments
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Chen, Wilbur Y., primary and Juang, Hann-ming Henry, additional
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- 1992
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160. Enhanced antibody responses to a detoxified lipopolysaccharide-group B meningococcal outer membrane protein vaccine are due to synergistic engagement of Toll-like receptors.
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Chen, Wilbur H., Basu, Subhendu, Bhattacharjee, Apurba K., and Cross, Alan S.
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IMMUNOGLOBULINS , *ENDOTOXINS , *VACCINES , *LIPOPOLYSACCHARIDES , *MEMBRANE proteins , *TOLL-like receptors - Published
- 2010
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161. Intranasal administration of a detoxified endotoxin vaccine protects mice against heterologous Gramnegative bacterial pneumonia.
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Chen, Wilbur H., Tae Jin Kang, Bhattacharjee, Apurba K., and Cross, Alan S.
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ENDOTOXINS , *GRAM-negative bacterial diseases , *VACCINES , *IMMUNIZATION , *LABORATORY mice , *SEPSIS , *IMMUNITY , *PNEUMONIA - Abstract
When given passively or elicited actively, antibodies induced by a detoxified Escherichia coli J5 mutant lipopolysaccharide (J5dLPS)-group B meningococcal outer membrane protein (-OMP) vaccine previously protected animals from lethal sepsis. To assess the use of this vaccine for the treatment of Gram-negative bacillary pneumonia, we vaccinated mice, with or without the adjuvant CpG, by intranasal (i.n.) or intraperitoneal (i.p.) routes of administration. Local and systemic IgG levels were 2-3 logs higher following i.p. immunization compared to i.n. However, i.n. immunization elicited both local and systemic IgA, unlike i.p. administration. The addition of CpG to the vaccine, by either route of administration, elicited greater levels of antibody. Intranasal immunization protected mice against lethal heterologous Gram-negative bacillary pneumonia and post-immunization serum and bronchoalveolar lavage fluid mediated enhanced bacterial killing with peritoneal and alveolar macrophages in vitro. We conclude that further studies on the use of J5dLPS-OMP for the prevention of nosocomial pneumonia are warranted. [ABSTRACT FROM AUTHOR]
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- 2008
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162. Active Immunization with a Detoxified Endotoxin Vaccine Protects against Lethal Polymicrobial Sepsis: Its Use with CpG Adjuvant and Potential Mechanisms.
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Opal, Steven M., Palardy, John E., Chen, Wilbur H., Parejo, Nicolas A., Bhattacharjee, Apurba K., and Cross, Alan S.
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SEPSIS ,IMMUNIZATION ,NEISSERIA meningitidis ,IMMUNOLOGICAL adjuvants ,ESCHERICHIA coli ,IMMUNOGLOBULINS - Abstract
Background. An experimental vaccine for sepsis, composed of detoxified Escherichia coli J5 lipopolysaccharide (LPS) complexed with the outer membrane protein (OMP) of Neisseria meningitidis group B, induces anti-core glycolipid antibody and has been tested in pilot studies in human volunteers. Methods. Mice were immunized with the LPS-J5/OMP vaccine with or without synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs as a vaccine adjuvant (CpG ODN). The efficacy of the vaccineinduced antibody response was tested in a cecal ligation and puncture model. Results. Immunization resulted in a >20-fold increase in anti-core glycolipid antibody levels, which were further increased 5-fold by the addition of CpG ODN, compared with the levels in mice in the control group. The vaccine provided a survival advantage after a cecal ligation and puncture was performed (P<.01) and sig- P<.01 significantly decreased the levels of bacteria in organs. Immunoglobulin G (IgG) anti-core glycolipid antibodies were decreased in mice to a significantly greater extent than were levels of total circulating IgG or IgG to the OMP part of the vaccine complex, suggesting specific epitope binding and clearance. Conclusions. These results indicate that the detoxified LPS-J5/OMP vaccine induces high levels of antibody against the core glycolipid of LPS and functions in vivo to promote clearance of gram-negative bacteria and improve the outcome of experimental polymicrobial intra-abdominal sepsis. [ABSTRACT FROM AUTHOR]
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- 2005
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163. High performance capillary electrophoresis of calmodulin
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Chan, Kai‐Foon J., primary and Chen, Wilbur H., additional
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- 1990
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164. Characterization of terminal NeuNAcα2–3Galß1–4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis.
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Tsai, Chao‐Ming, Chen, Wilbur H., and Balakonis, Paula A.
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Group B and C Neisseria meningitidis are the major cause of meningococcal disease in the United States and in Europe. N.meningitidis lipooligosaccharide (LOS), a major surface antigen, can be divided into 12 immunotypes of which L1 through L8 were found among Group B and C organisms. Groups B and C but not Group A may sialylate their LOSs with N‐acetylneuraminic acid (NeuNAc) at the nonreducing end because they synthesize CMP‐NeuNAc. Using sialic acid–galactose binding lectins as probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis leukoagglutinin (MAL), which recognizes NeuNAcα2–3Galß1–4GlcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAcα2–6Gal sequence. The combination of SDS–PAGE and MAL‐blot analyses revealed that these six LOSs contained only the NeuNAcα2–3Galß1–4GlcNAc trisaccharide sequence in their 4.1 kDa LOS components, which have a common terminal lacto‐N‐neotetraose (LNnT, Galß1–4GlcNAcß1–3Galß1–4Glc) structure when nonsialylated as shown by previous studies. The LOS‐lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves α2→3 linked sialic acid. Methylation analysis of a representative LOS (L2) confirmed that NeuNAc is 2→3 linked to Gal. Thus, these LOSs structurally mimic certain glycolipids, i.e., paragloboside (LNnT‐ceramide) and sialylparagloboside and some glycoproteins in having LNnT and N‐acetyllactosamine sequences, respectively, with or without α2→3 linked NeuNAc. The molecular mimicry of the LOSs may play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man. [ABSTRACT FROM PUBLISHER]
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- 1998
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165. Intranasal administration of a detoxified endotoxin vaccine protects mice against heterologous Gram-negative bacterial pneumonia
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Chen, Wilbur H., Kang, Tae Jin, Bhattacharjee, Apurba K., and Cross, Alan S.
- Abstract
When given passively or elicited actively, antibodies induced by a detoxified Escherichia coliJ5 mutant lipopolysaccharide (J5dLPS)-group B meningococcal outer membrane protein (-OMP) vaccine previously protected animals from lethal sepsis. To assess the use of this vaccine for the treatment of Gram-negative bacillary pneumonia, we vaccinated mice, with or without the adjuvant CpG, by intranasal (i.n.) or intraperitoneal (i.p.) routes of administration. Local and systemic IgG levels were 2—3 logs higher following i.p. immunization compared to i.n. However, i.n. immunization elicited both local and systemic IgA, unlike i.p. administration. The addition of CpG to the vaccine, by either route of administration, elicited greater levels of antibody. Intranasal immunization protected mice against lethal heterologous Gram-negative bacillary pneumonia and post-immunization serum and broncho-alveolar lavage fluid mediated enhanced bacterial killing with peritoneal and alveolar macrophages in vitro. We conclude that further studies on the use of J5dLPS-OMP for the prevention of nosocomial pneumonia are warranted.
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- 2008
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166. A case for immunization against nosocomial infections
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Cross, Alan S., Chen, Wilbur H., and Levine, Myron M.
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Immunization is a highly effective public health measure that reduces the incidence of infectious diseases, yet there has been relatively little effort toward the development of vaccines for nosocomial infections. Many nosocomial infections originate on mucosal surfaces (e.g., respiratory or gastrointestinal mucosa). As patients who are hospitalized once are more likely to be hospitalized again, we propose a prime‐boost immunization strategy, whereby a priming dose of vaccine for a nosocomial infection is administered mucosally. Upon readmission, a parenteral boost would elicit a rapid immune response locally and systemically. Such a strategy could reduce or ameliorate nosocomial infections and perhaps limit dissemination of nosocomial pathogens. Thus, a more aggressive effort to develop vaccines for nosocomial infections is warranted.
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- 2008
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167. Role of Bacillus anthracis Spore Structures in Macrophage Cytokine Responses
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Basu, Subhendu, Kang, Tae Jin, Chen, Wilbur H., Fenton, Matthew J., Baillie, Les, Hibbs, Steve, and Cross, Alan S.
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The innate immune response of macrophages (M) to spores, the environmentally acquired form of Bacillus anthracis, is poorly characterized. We therefore examined the early M cytokine response to B. anthracis spores, before germination. M were exposed to bacilli and spores of Sterne strain 34F2 and its congenic nongerminating mutant (gerH), and cytokine expression was measured by real-time PCR and an enzyme-linked immunosorbent assay. The exosporium spore layer was retained (exo+) or removed by sonication (exo–). Spores consistently induced a strong cytokine response, with the exo–spores eliciting a two- to threefold-higher response than exo+spores. The threshold for interleukin-1{szligbeta} (IL-1{szligbeta}) production by wild-type M was significantly lower than that required for tumor necrosis factor alpha expression. Cytokine production was largely dependent on MyD88, suggesting Toll-like receptor involvement; however, the expression of beta interferon in MyD88–/–M suggests involvement of a MyD88-independent pathway. We conclude that (i) the B. anthracis spore is not immunologically inert, (ii) the exosporium masks epitopes recognized by the M, (iii) the M cytokine response to B. anthracis involves multiple pattern recognition receptors and signaling pathways, and (iv) compared to other cytokines, IL-1{szligbeta} is expressed at a lower spore concentration.
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- 2007
168. Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023.
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Hills, Susan L., Poehling, Katherine A., Chen, Wilbur H., and Staples, J. Erin
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TICK-borne diseases , *DRUG approval , *VIRAL vaccines , *VIRAL encephalitis , *MEDICAL protocols , *VACCINE effectiveness , *PATIENT safety , *TRAVEL hygiene , *DISEASE risk factors , *INFECTIOUS disease transmission , *SYMPTOMS , *DISEASE complications - Abstract
Tick-borne encephalitis (TBE) virus is focally endemic in parts of Europe and Asia. The virus is primarily transmitted to humans by the bites of infected Ixodes species ticks but can also be acquired less frequently by alimentary transmission. Other rare modes of transmission include through breastfeeding, blood transfusion, solid organ transplantation, and slaughtering of viremic animals. TBE virus can cause acute neurologic disease, which usually results in hospitalization, often permanent neurologic or cognitive sequelae, and sometimes death. TBE virus infection is a risk for certain travelers and for laboratory workers who work with the virus. In August 2021, the Food and Drug Administration approved Ticovac TBE vaccine for use among persons aged ≥1 year. This report summarizes the epidemiology of and risks for infection with TBE virus, provides information on the immunogenicity and safety of TBE vaccine, and summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of TBE vaccine among U.S. travelers and laboratory workers. The risk for TBE for most U.S. travelers to areas where the disease is endemic is very low. The risk for exposure to infected ticks is highest for persons who are in areas where TBE is endemic during the main TBE virus transmission season of April--November and who are planning to engage in recreational activities in woodland habitats or who might be occupationally exposed. All persons who travel to areas where TBE is endemic should be advised to take precautions to avoid tick bites and to avoid the consumption of unpasteurized dairy products because alimentary transmission of TBE virus can occur. TBE vaccine can further reduce infection risk and might be indicated for certain persons who are at higher risk for TBE. The key factors in the risk-benefit assessment for vaccination are likelihood of exposure to ticks based on activities and itinerary (e.g., location, rurality, season, and duration of travel or residence). Other risk-benefit considerations should include 1) the rare occurrence of TBE but its potentially high morbidity and mortality, 2) the higher risk for severe disease among certain persons (e.g., older persons aged ≥60 years), 3) the availability of an effective vaccine, 4) the possibility but low probability of serious adverse events after vaccination, 5) the likelihood of future travel to areas where TBE is endemic, and 6) personal perception and tolerance of risk. ACIP recommends TBE vaccine for U.S. persons who are moving or traveling to an area where the disease is endemic and will have extensive exposure to ticks based on their planned outdoor activities and itinerary. Extensive exposure can be considered based on the duration of travel and frequency of exposure and might include shorter-term (e.g., <1 month) travelers with daily or frequent exposure or longer-term travelers with regular (e.g., a few times a month) exposure to environments that might harbor infected ticks. In addition, TBE vaccine may be considered for persons who might engage in outdoor activities in areas where ticks are likely to be found, with a decision to vaccinate made on the basis of an assessment of their planned activities and itinerary, risk factors for a poor medical outcome, and personal perception and tolerance of risk. In the laboratory setting, ACIP recommends TBE vaccine for laboratory workers with a potential for exposure to TBE virus. [ABSTRACT FROM AUTHOR]
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- 2023
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169. Pre-existing Helicobacter pylori serum IgG enhances the vibriocidal antibody response to CVD 103-HgR live oral cholera vaccine in Malian adults.
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Muhsen, Khitam, Sow, Samba O., Tapia, Milagritos D., Haidara, Fadima C., Reymann, Mardi, Asato, Valeria, Chen, Wilbur H., Pasetti, Marcela F., and Levine, Myron M.
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HELICOBACTER pylori infections ,IMMUNOGLOBULIN G ,CHOLERA vaccines ,ENZYME-linked immunosorbent assay ,IMMUNE response - Abstract
Accumulating evidence indicates that persistent Helicobacter pylori gastric infection influences immune responses to oral enteric vaccines. We studied the association between pre-existing H. pylori serum IgG and serum pepsinogens levels (PGs) as markers of gastric inflammation and the immune response to single-dose live oral cholera vaccine CVD 103-HgR in Malian adults. Baseline sera obtained during a phase 2 safety/immunogenicity clinical trial of cholera vaccine CVD 103-HgR among 93 healthy Malian adults were tested for H. pylori IgG antibodies and PGI and PGII levels using enzyme linked immunosorbent assays. Overall 74/93 (80%) vaccine recipients were H. pylori IgG seropositive at baseline. Vibriocidal antibody seroconversion (≥ fourfold increase 14 days following administration of CVD 103-HgR compared to baseline) among vaccine recipients was 56%. However, vibriocidal antibody seroconversion was markedly higher among H. pylori seropositives than seronegatives 64% vs. 26% (p = 0.004); adjusted relative risk: 2.20 (95% confidence intervals 1.00–4.80; p = 0.049). Among H. pylori seropositive vaccine recipients, there were no significant associations between PGI, PGII and PGI:PGII levels and vibriocidal seroconversion. The enhanced seroconversion to oral cholera vaccine CVD 103-HgR among H. pylori seropositive African adults provides further evidence of the immunomodulating impact of H. pylori on oral vaccine immunogenicity. [ABSTRACT FROM AUTHOR]
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- 2020
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170. Association between Methicillin-Resistant Staphylococcus aureusColonization and Infection May Not Differ by Age Group
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Ajao, Adebola O., Harris, Anthony D., Johnson, J. Kristie, Roghmann, Mary-Claire, Perencevich, Eli N., Schweizer, Marin L., Zhan, Min, Chen, Wilbur H., and Furuno, Jon P.
- Abstract
We assessed whether age modified the association between methicillin-resistant Staphylococcus aureus(MRSA) anterior nares colonization and subsequent infection. Among 7,405 patients (9,511 admissions), MRSA colonization was significantly associated with infection (adjusted odds ratio, 13.7 [95% confidence interval, 7.325.7]) but did not differ significantly by age group.
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- 2013
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171. Influenza Vaccines for Older Persons: Progress and Pitfalls.
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Neuzil, Kathleen M. and Chen, Wilbur H.
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INFLUENZA prevention , *INFLUENZA treatment , *INFLUENZA vaccines , *RESPIRATORY infections , *FRAGILITY (Psychology) , *CLINICAL trials , *DIAGNOSIS - Abstract
The article examines the effectiveness of influenza vaccines for older persons. It highlights the impact of lack of confidence in vaccine performance on vaccine uptake as well as the consequences of influenza illnesses. Also emphasized is the significant of frailty as predictor of vaccine performance in clinical trials and case-control studies.
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- 2017
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172. Dynamical Extended Range Forecasting (DERF) at the National Meteorological Center
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Tracton, M. Steven, primary, Mo, Kingtse, additional, Chen, Wilbur, additional, Kalnay, Eugenia, additional, Kistler, Robert, additional, and White, Glenn, additional
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- 1989
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173. Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial.
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Sahly, Hana M El, Yildirim, Inci, Frey, Sharon E, Winokur, Patricia, Jackson, Lisa A, Bernstein, David I, Creech, C Buddy, Chen, Wilbur H, Rupp, Richard E, Whitaker, Jennifer A, Phadke, Varun, Hoft, Daniel F, Ince, Dilek, Brady, Rebecca C, Edwards, Kathryn M, Ortiz, Justin R, Berman, Megan A, Weiss, Julia, Wegel, Ashley, and Group, DMID 17-0090 Study
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AVIAN influenza , *CLINICAL trials , *IMMUNE response , *CLINICAL trial registries , *ANTIBODY titer - Abstract
Background Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown. Methods We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays. Results We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group. Conclusions Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens. Clinical Trials Registration NCT03738241. [ABSTRACT FROM AUTHOR]
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- 2024
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174. Immunogenicity and safety of varying dosages of a fifth-wave influenza A/H7N9 inactivated vaccine given with and without AS03 adjuvant in healthy adults.
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Jackson, Lisa A., Stapleton, Jack T., Walter, Emmanuel B., Chen, Wilbur H., Rouphael, Nadine G., Anderson, Evan J., Neuzil, Kathleen M., Winokur, Patricia L., Smith, Michael J., Schmader, Kenneth E., Swamy, Geeta K., Thompson, Amelia B., Mulligan, Mark J., Rostad, Christina A., Cross, Kaitlyn, Tsong, Rachel, Wegel, Ashley, and Roberts, Paul C.
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H7N9 Influenza , *IMMUNE response , *INFLUENZA , *VACCINES , *ANTIBODY titer , *INFLUENZA vaccines - Abstract
Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage viruses, which differed antigenically from those of earlier waves, predominated. In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.75, 7.5, and 15 µg of hemagglutinin (HA) with AS03A adjuvant and at doses of 15 and 45 µg of HA without adjuvant. Two doses of adjuvanted vaccine were required to induce HA inhibition (HI) antibody titers ≥ 40 in most participants. After two doses of the 15 µg H7N9 formulation, given with or without AS03 adjuvant, the proportion achieving a HI titer ≥ 40 against the vaccine strain at 21 days after the second vaccination was 65 % (95 % CI, 57 %-73 %) and 0 % (95 % CI, 0 %-4%), respectively. Among those who received two doses of the 15 µg adjuvanted formulation the proportion with HI titer ≥ 40 at 21 days after the second vaccination was 76 % (95 % CI, 66 %-84 %) in those 19–64 years of age and 49 % (95 % CI, 37 %-62 %) in those ≥ 65 years of age. Responses to the adjuvanted vaccine formulations did not vary by HA content. Antibody responses declined over time and responses against drifted H7N9 strains were diminished. Overall, the vaccines were well tolerated but, as expected, adjuvanted vaccines were associated with more frequent solicited systemic and local adverse events. AS03 adjuvant improved the immune responses to an inactivated fifth–wave H7N9 influenza vaccine, particularly in younger adults, but invoked lower responses to drifted H7N9 strains. These findings may inform future influenza pandemic preparedness strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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175. 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
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Sow, Samba O., Tapia, Milagritos D., Chen, Wilbur H., Haidara, Fadima C., Kotloff, Karen L., Pasetti, Marcela F., Blackwelder, William C., Traoré, Awa, Tamboura, Boubou, Doumbia, Moussa, Diallo, Fatoumata, Coulibaly, Flanon, Onwuchekwa, Uma, Kodio, Mamoudou, Tennant, Sharon M., Reymann, Mardi, Lam, Diana F., Gurwith, Marc, Lock, Michael, Yonker, Thomas, Smith, Jonathan, Simon, Jakub K., and Levine, Myron M.
- Abstract
ABSTRACTReactive 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 choleraeO1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing =2 × 108CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required =2 × 109CFU 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 × 108-CFU standard dose (n= 50) or a =2 × 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.)
- Published
- 2018
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176. The Live Attenuated Cholera Vaccine CVD 103-HgR Primes Responses to the Toxin-Coregulated Pilus Antigen TcpA in Subjects Challenged with Wild-Type Vibrio cholerae
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Mayo-Smith, Leslie M., Simon, Jakub K., Chen, Wilbur H., Haney, Douglas, Lock, Michael, Lyon, Caroline E., Calderwood, Stephen B., Kirkpatrick, Beth D., Cohen, Mitchell, Levine, Myron M., Gurwith, Marc, and Harris, Jason B.
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ABSTRACTOne potential advantage of live attenuated bacterial vaccines is the ability to stimulate responses to antigens which are only expressed during the course of infection. To determine whether the live attenuated cholera vaccine CVD 103-HgR (Vaxchora) results in antibody responses to the in vivo-induced toxin-coregulated pilus antigen TcpA, we measured IgA and IgG responses to Vibrio choleraeO1 El Tor TcpA in a subset of participants in a recently reported experimental challenge study. Participants were challenged with V. choleraeO1 El Tor Inaba N16961 either 10 days or 90 days after receiving the vaccine or a placebo. Neither vaccination nor experimental infection with V. choleraealone resulted in a robust TcpA IgG or IgA response, but each did elicit a strong response to cholera toxin. However, compared to placebo recipients, vaccinees had a marked increase in IgG TcpA antibodies following the 90-day challenge, suggesting that vaccination with CVD 103-HgR resulted in priming for a subsequent response to TcpA. No such difference between vaccine and placebo recipients was observed for volunteers challenged 10 days after vaccination, indicating that this was insufficient time for vaccine-induced priming of the TcpA response. The priming of the response to TcpA and potentially other antigens expressed in vivoby attenuated V. choleraemay have relevance to the maintenance of immunity in areas where cholera is endemic.
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- 2016
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177. Safety, Reactogenicity, and Immunogenicity of Inactivated Monovalent Influenza A(H5N1) Virus Vaccine Administered With or Without AS03 Adjuvant.
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Chen, Wilbur H., Jackson, Lisa A., Edwards, Kathryn M., Keitel, Wendy A., Hill, Heather, Noah, Diana L., Creech, C. Buddy, Patel, Shital M., Mangal, Brian, and Kotloff, Karen L.
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INFLUENZA treatment , *INFLUENZA vaccination research , *PANDEMICS , *IMMUNE response , *VACCINE research , *HEMAGGLUTINATION tests - Abstract
Background. The national stockpile for influenza pandemic preparedness includes vaccines against an array of strains and adjuvants that could be utilized to induce immunologic priming as a pandemic wave emerges. We assessed the feasibility of a strategy that allows the flexibility of postmanufacture mixture of vaccine and adjuvant at the point of care.Methods. We conducted a randomized, double-blind, multicenter trial among healthy adults aged 18–49 years who received 2 doses of inactivated influenza A/Indonesia/05/2005 (H5N1 clade 2.2.3) virus vaccine containing either 3.75, 7.5, or 15 µg of hemagglutinin (HA) with or without AS03 adjuvant, administered 21 days apart. Subjects were observed for local (injection site) and systemic reactogenicity and adverse events. Sera were tested for hemagglutination inhibition (HAI) and microneutralization (MN) antibody levels against the homologous strain and 4 heterologous avian strains.Results. Vaccine containing ASO3 adjuvant was associated with significantly more local reactions compared with nonadjuvanted vaccine, but these were short-lived and resolved spontaneously. Although the immune response to nonadjuvanted vaccine was poor, 2 doses of AS03-adjuvanted vaccine containing as little as 3.75 µg of HA elicited robust immune responses resulting in seroprotective titers (≥1:40) to the homologous strain in ≥86% of subjects by HAI and in 95% of subjects by MN. Cross-clade antibody responses were also observed with AS03-adjuvanted vaccine, but not nonadjuvanted vaccine.Conclusions. AS03 adjuvant formulated with inactivated vaccine at the administration site significantly enhanced the immune responses to H5N1 vaccine and has the potential to markedly improve vaccine responses and accelerate delivery during an influenza pandemic.Clinical Trials Registration. NCT01317758. [ABSTRACT FROM PUBLISHER]
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- 2014
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178. Recommended Adult Immunization Schedule, United States, 2023.
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Murthy, Neil, Wodi, A. Patricia, Cineas, Sybil, Ault, Kevin A., Lee, Grace M., Wharton, Melinda, Bahta, Lynn, Bell, Beth P., Brooks, Oliver, Chen, Wilbur H., Daley, Matthew F., Kotton, Camille Nelson, Loehr, Jamie, Long, Sarah S., McNally, Veronica V., Poehling, Katherine A., Sánchez, Pablo J., Shah, Nirav D., Talbot, Helen Keipp, and McNally, Veronica
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IMMUNIZATION , *ADULTS , *SCHEDULING , *VACCINATION - Abstract
This article provides immunization recommendations from the Advisory Committee on Immunization Practices (ACIP) for adults aged 19 years or older. The purpose of the immunization schedule is to consolidate and summarize updates to ACIP recommendations on vaccination of adults and to assist providers in implementing current ACIP recommendations. [ABSTRACT FROM AUTHOR]
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- 2023
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179. Safety and immunogenicity of monovalent H7N9 influenza vaccine with AS03 adjuvant given sequentially or simultaneously with a seasonal influenza vaccine: A randomized clinical trial.
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Ortiz, Justin R., Spearman, Paul W., Goepfert, Paul A., Cross, Kaitlyn, Buddy Creech, C., Chen, Wilbur H., Parker, Susan, Overton, Edgar T., Dickey, Michelle, Logan, Heather L., Wegel, Ashley, and Neuzil, Kathleen M.
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VACCINE trials , *H7N9 Influenza , *SEASONAL influenza , *INFLUENZA vaccines , *CLINICAL trials , *INFLUENZA , *PANDEMICS - Abstract
Influenza A/H7N9 viruses have pandemic potential. We conducted an open-label, randomized, controlled trial of AS03-adjuvanted 2017 inactivated influenza A/H7N9 vaccine (H7N9 IIV) in healthy adults. Group 1 received H7N9 IIV and seasonal quadrivalent influenza vaccine (IIV4) simultaneously, followed by H7N9 IIV three weeks later. Group 2 received IIV4 alone and then two doses of H7N9 IIV at three-week intervals. Group 3 received one dose of IIV4. We used hemagglutination inhibition (HAI) and microneutralization (MN) assays to measure geometric mean titers and seroprotection (≥1:40 titer) to vaccine strains and monitored for safety. Among 149 subjects, seroprotection by HAI three weeks after H7N9 IIV dose 2 was 51% (95 %CI 37%-65%) for Group 1 and 40% (95 %CI 25%-56%) for Group 2. Seroprotection by MN at the same timepoint was 84% (95 %CI 72%-93%) for Group 1 and 74% (95 %CI 60%-86%) for Group 2. By 180 days after H7N9 IIV dose 2, seroprotection by HAI or MN was low for Groups 1 and 2. Responses measured by HAI and MN against each IIV4 strain three weeks after IIV4 vaccination were similar in all groups. Solicited local and systemic reactions were similar after a single vaccination, while those receiving simultaneous H7N9 and IIV4 had slightly more reactogenicity. There were no serious adverse events or medically-attended adverse events related to study product receipt. Adjuvanted H7N9 IIV was modestly immunogenic whether administered simultaneously or sequentially with IIV4, though responses declined by 180 days. IIV4 was immunogenic regardless of schedule. Clinical Trials Registration: NCT03318315 [ABSTRACT FROM AUTHOR]
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- 2022
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180. A Phase 2a randomized, single-center, double-blind, placebo-controlled study to evaluate the safety and preliminary efficacy of oral iOWH032 against cholera diarrhea in a controlled human infection model.
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Erdem, Rahsan, Ambler, Gwen, Al-Ibrahim, Mohamed, Fraczek, Katarzyna, Dong, Steven D., Gast, Christopher, Mercer, Laina D., Raine, Michael, Tennant, Sharon M., Chen, Wilbur H., de Hostos, Eugenio L., and Choy, Robert K. M.
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CYSTIC fibrosis transmembrane conductance regulator , *CHOLERA , *CHOLERA vaccines , *VIBRIO infections - Abstract
Cholera remains a major cause of infectious diarrhea globally. Despite the increased availability of cholera vaccines, there is still an urgent need for other effective interventions to reduce morbidity and mortality. Furthermore, increased prevalence of antibiotic-resistant Vibrio cholerae threatens the use of many drugs commonly used to treat cholera. We developed iOWH032, a synthetic small molecule inhibitor of the cystic fibrosis transmembrane conductance regulator chloride channel, as an antisecretory, host-directed therapeutic for cholera. In the study reported here, we tested iOWH032 in a Phase 2a cholera controlled human infection model. Forty-seven subjects were experimentally infected with V. cholerae El Tor Inaba strain N16961 in an inpatient setting and randomized to receive 500 mg iOWH032 or placebo by mouth every 8 hours for 3 days to determine the safety and efficacy of the compound as a potential treatment for cholera. We found that iOWH032 was generally safe and achieved a mean (± standard deviation) plasma level of 4,270 ng/mL (±2,170) after 3 days of oral dosing. However, the median (95% confidence interval) diarrheal stool output rate for the iOWH032 group was 25.4 mL/hour (8.9, 58.3), compared to 32.6 mL/hour (15.8, 48.2) for the placebo group, a reduction of 23%, which was not statistically significant. There was also no significant decrease in diarrhea severity and number or frequency of stools associated with iOWH032 treatment. We conclude that iOWH032 does not merit future development for treatment of cholera and offer lessons learned for others developing antisecretory therapeutic candidates that seek to demonstrate proof of principle in a cholera controlled human infection model study. Trial registration: This study is registered with ClinicalTrials.gov as NCT04150250. Author summary: Cholera, a disease caused by infection with the bacterium Vibrio cholerae, remains a major cause of diarrheal illness and death, particularly in settings with poor sanitation and hygiene. We developed a synthetic chemical, named "iOWH032," as a potential treatment for cholera, which is administered as oral tablets. The chemical acts by blocking secretions from cells in the intestine, and thereby was expected to prevent fluid loss and dehydration caused by cholera illness. We tested iOWH032 in a clinical study using a cholera human challenge model. Study volunteers were intentionally infected with V. cholerae in an inpatient clinic setting to better study the effects of iOWH032 on infected individuals. This challenge model had been used previously to test cholera vaccine candidates, but this study represents the first test of a potential cholera treatment using the model. We found that treatment of individuals with iOWH032 was safe, but did not result in a significant reduction of cholera illness, based on several different measurements of diarrheal symptoms and severity. This study demonstrates how human challenge models incorporating a relatively small number of subjects can help support decision-making about potential new therapeutics and other interventions for infectious diseases. [ABSTRACT FROM AUTHOR]
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- 2021
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181. Linked vaccination coverage surveys plus serosurveys among Ethiopian toddlers undertaken three years apart to compare coverage and serologic evidence of protection in districts implementing the RED-QI approach.
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Campbell, James D., Pasetti, Marcela F., Oot, Lisa, Adam, Zenaw, Tefera, Mesfin, Beyane, Berhane, Mulholland, Nigisti, Steinglass, Robert, Krey, Rebecca, Chen, Wilbur H., Blackwelder, William C., and Levine, Myron M.
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VACCINATION , *TODDLERS , *MEASLES vaccines , *HEALTH facilities , *TETANUS vaccines , *MIDDLE-income countries , *VACCINATION coverage - Abstract
• A seroprotective tetanus titer indicates a toddler has received pentavalent vaccine. • Serosurveys document increased seroprevalence post-measles vaccination campaigns. • Vaccination coverage/serosurveys can assess interventions to improve immunizations. In low and middle-income countries, estimating the proportion of vaccinated toddlers in a population is important for controlling vaccine-preventable diseases by identifying districts where immunization services need strengthening. Estimates measured before and several years after specific interventions can assess program performance. However, employing different methods to derive vaccination coverage estimates often yield differing results. Linked vaccination coverage surveys and seroprotection surveys performed among ~300 toddlers 12–23 months of age in districts (woredas), one per region, of Ethiopia (total, ~900 toddlers) in 2013 to estimate the proportion vaccinated with tetanus toxoid (a proxy for pentavalent vaccine) and measles vaccine. The surveys were followed by implementation of the Reaching Every District using Quality Improvement (RED-QI) approach to strengthen the immunization system. Linked coverage/serosurveys were repeated in 2016 to assess effects of the interventions on vaccination coverage. Indicators included "documented coverage" (vaccination card and/or health facility register records) and "crude coverage" (documented plus parent/caretaker recall for children without cards). Seroprotection thresholds were IgG-ELISA tetanus antitoxin ≥0.05 IU/ml and plaque reduction neutralization (PRN) measles titers ≥120 mIU/ml. Improved markers in 2016 over 2013 include coverage of pentavalent vaccination, vaccination timeliness, and fewer missed opportunities to vaccinate. In parallel, tetanus seroprotection increased in the 3 woredas from 59.6% to 79.1%, 72.9% to 83.7%, and 94.3 to 99.3%. In 2015, the Ethiopian government conducted supplemental measles mass vaccination campaigns in several regions including one that involved a project woreda and the campaign overlapped with the RED-QI intervention timeframe; protective measles PRN titers there rose from 31.0% to 50.0%. The prevalence of seroprotective titers of tetanus antitoxin (stimulated by tetanus toxoid components within pentavalent vaccine) provides a reliable biomarker to identify children who received pentavalent vaccine. In the three study woredas, the RED-QI intervention appeared to improve immunization service delivery, as documented by enhanced pentavalent vaccine coverage, vaccination timeliness, and fewer missed vaccination opportunities. A measles mass vaccination campaign was followed by a markedly increased prevalence of measles PRN antibodies. Collectively, these observations suggest that wider implementation of RED-QI can strengthen immunization, and periodic linked vaccination surveys/serosurveys can monitor changes. [ABSTRACT FROM AUTHOR]
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- 2021
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182. Fourth Controlled Human Infection Model (CHIM) meeting, CHIM regulatory issues, May 24, 2023.
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Cavaleri, Marco, Kaslow, David, Boateng, Eric, Chen, Wilbur H., Chiu, Christopher, Choy, Robert K.M., Correa-Oliveira, Rodrigo, Durbin, Anna, Egesa, Moses, Gibani, Malick, Kapulu, Melissa, Katindi, Melba, Olotu, Ally, Pongsuwan, Pongphaya, Simuyandi, Michelo, Speder, Bruno, Talaat, Kawsar R., Weller, Charlie, Wills, Bridget, and Baay, Marc
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MEDICAL personnel , *CURRENT good manufacturing practices , *INFECTION control , *LOW-income countries , *FIELD research - Abstract
Many aspects of Controlled Human Infection Models (CHIMs, also known as human challenge studies and human infection studies) have been discussed extensively, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on regulation of CHIM studies, bringing together scientists and regulators from high-, middle-, and low-income countries, to discuss barriers and hurdles in CHIM regulation. Valuable initiatives for regulation of CHIMs have already been undertaken but further capacity building remains essential. The Wellcome Considerations document is a good starting point for further discussions. • The time is right to discuss the regulation of first-in-human studies, including CHIM studies, in LMIC. • The biggest remaining hurdle in many countries is the lack of a regulatory framework for conducting CHIM studies. • Currently, CHIM studies should not be performed in children, except when using an approved, live-attenuated vaccines. • Engagement should include regulators, health care professionals, potential study participants, and the community. • CHIMs could establish vaccine effect on reducing pathogen shedding and transmission not readily established in field trials. [ABSTRACT FROM AUTHOR]
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- 2024
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183. Use of Ebola Vaccine: Expansion of Recommendations of the Advisory Committee on Immunization Practices To Include Two Additional Populations - United States, 2021.
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Malenfant, Jason H., Joyce, Allison, Choi, Mary J., Cossaboom, Caitlin M., l, Amy N., Harcourt, Brian H., Atmar, Robert L., Villanueva, Julie M., Bell, Beth P., Hahn, Christine, Loehr, Jamie, Davey, Richard T., Sprecher, Armand, Kraft, Colleen S., Shoemaker, Trevor, Montgomery, Joel M., Helfand, Rita, Damon, Inger K., Frey, Sharon E., and Chen, Wilbur H.
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VACCINATION , *IMMUNIZATION , *VIRAL vaccines , *ATTITUDE (Psychology) , *EBOLA virus , *SURVEYS , *HEALTH literacy , *VACCINE effectiveness , *DESCRIPTIVE statistics - Abstract
On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff members at biosafety level 4 facilities in the United States (1). [ABSTRACT FROM AUTHOR]
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- 2022
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184. For now, it's unethical to use human challenge studies for SARS-CoV-2 vaccine development.
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Kahn, Jeffrey P., Henry, Leslie Meltzer, Mastroianni, Anna C., Chen, Wilbur H., and Macklin, Ruth
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VACCINE development , *SARS-CoV-2 , *COVID-19 , *MEDICAL personnel , *HUMAN experimentation - Published
- 2020
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185. Characteristics of regulatory T-cell populations before and after Ty21a typhoid vaccination in children and adults.
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Rudolph, Mark E., McArthur, Monica A., Magder, Laurence S., Barnes, Robin S., Chen, Wilbur H., and Sztein, Marcelo B.
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TYPHOID fever , *VACCINATION of children , *ADULT-child relationships , *SALMONELLA enterica serovar Typhi , *T cells - Abstract
Typhoid fever, caused by the pathogen Salmonella enterica serovar Typhi (S. Typhi), is a serious global health concern. Challenge studies with wild type S. Typhi identified associations between gut-homing regulatory T cells (Treg) and development of typhoid disease. Whether oral live-attenuated Ty21a vaccination induces gut-homing Treg remains unclear. Here, we analyze pediatric and adult Treg pre- and post-Ty21a vaccination in an autologous S. Typhi-antigen presentation model to address this knowledge gap. We show that peripheral memory Treg populations change from childhood to adulthood, but not following Ty21a vaccination. Unsupervised dimensionality reduction with t-distributed stochastic neighbor embedding (tSNE) identifies homing, memory, and functional features which evidence age-associated maturation of multifunctional S. Typhi-responsive Treg, which were not impacted by Ty21a vaccination. These findings improve understanding of pediatric regulatory T cells, while identifying age-related differences in S. Typhi-responsive Treg, which may aid in the development of improved pediatric vaccination strategies against S. Typhi. [ABSTRACT FROM AUTHOR]
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- 2019
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186. Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection.
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Haney, Douglas J., Lock, Michael D., Gurwith, Marc, Simon, Jakub K., Ishioka, Glenn, Cohen, Mitchell B., Kirkpatrick, Beth D., Lyon, Caroline E., Chen, Wilbur H., Sztein, Marcelo B., Levine, Myron M., and Harris, Jason B.
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CHOLERA vaccines , *LIPOPOLYSACCHARIDES , *B cells , *VIBRIO cholerae , *SEROCONVERSION - Abstract
Background The single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naïve adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1–2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response. Methods In a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera. Results There was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = −0.56, p < 0.001). Discussion Oral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection. Clinical trials registration: NCT01895855. [ABSTRACT FROM AUTHOR]
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- 2018
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187. In vitro–in vivo correlations for nicotine transdermal delivery systems evaluated by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under the influence of transient heat application.
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Shin, Soo Hyeon, Thomas, Sherin, Raney, Sam G., Ghosh, Priyanka, Hammell, Dana C., El-Kamary, Samer S., Chen, Wilbur H., Billington, M. Melissa, Hassan, Hazem E., and Stinchcomb, Audra L.
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THERAPEUTIC use of nicotine , *SKIN permeability , *TRANSDERMAL medication , *BIOAVAILABILITY , *PHARMACOKINETICS , *DRUG delivery systems - Abstract
The in vitro permeation test (IVPT) has been widely used to characterize the bioavailability (BA) of compounds applied on the skin. In this study, we performed IVPT studies using excised human skin ( in vitro ) and harmonized in vivo human serum pharmacokinetic (PK) studies to evaluate the potential in vitro – in vivo correlation (IVIVC) of nicotine BA from two, matrix-type, nicotine transdermal delivery systems (TDS). The study designs used for both in vitro and in vivo studies included 1 h of transient heat (42 ± 2 °C) application during early or late time periods post-dosing. The goal was to evaluate whether any IVIVC observed would be evident even under conditions of heat exposure, in order to investigate further whether IVPT may have the potential to serve as a possible surrogate method to evaluate the in vivo effects of heat on the bioavailability of a drug delivered from a TDS. The study results have demonstrated that the BA of nicotine characterized by the IVPT studies correlated with and was predictive of the in vivo BA of nicotine from the respective TDS, evaluated under the matched study designs and conditions. The comparisons of single parameters such as steady-state concentration, heat-induced increase in partial AUCs and post-treatment residual content of nicotine in TDS from the in vitro and in vivo data sets showed no significant differences ( p ≥ 0.05). In addition, a good point-to-point IVIVC (Level A correlation) for the entire study duration was achieved by predicting in vivo concentrations of nicotine using two approaches: Approach I requiring only an in vitro data set and Approach II involving deconvolution and convolution steps. The results of our work suggest that a well designed IVPT study with adequate controls can be a useful tool to evaluate the relative effects of heat on the BA of nicotine from TDS with different formulations. [ABSTRACT FROM AUTHOR]
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- 2018
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188. Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021.
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Paz-Bailey, Gabriela, Adams, Laura, Wong, Joshua M., Poehling, Katherine A., Chen, Wilbur H., McNally, Veronica, Atmar, Robert L., and Waterman, Stephen H.
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VIRAL vaccines , *IMMUNIZATION , *DENGUE , *FLAVIVIRUSES , *MOSQUITOES - Abstract
Dengue is a vectorborne infectious disease caused by dengue viruses (DENVs), which are predominantly transmitted by Aedes aegypti and Aedes albopictus mosquitos. Dengue is caused by four closely related viruses (DENV-1-4), and a person can be infected with each serotype for a total of four infections during their lifetime. Areas where dengue is endemic in the United States and its territories and freely associated states include Puerto Rico, American Samoa, the U.S. Virgin Islands, the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the Dengvaxia vaccine in the United States. The vaccine is a live-attenuated, chimeric tetravalent dengue vaccine built on a yellow fever 17D backbone. Dengvaxia is safe and effective in reducing dengue-related hospitalizations and severe dengue among persons who have had dengue infection in the past. Previous natural infection is important because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination. Dengvaxia was licensed by the Food and Drug Administration for use among children and adolescents aged 9-16 years (referred to in this report as children). ACIP recommends vaccination with Dengvaxia for children aged 9-16 having evidence of a previous dengue infection and living in areas where dengue is endemic. Evidence of previous dengue infection, such as detection of anti-DENV immunoglobulin G with a highly specific serodiagnostic test, will be required for eligible children before vaccination. [ABSTRACT FROM AUTHOR]
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- 2021
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189. Tularemia vaccine: Safety, reactogenicity, “Take” skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain – A phase 2 randomized clinical Trial.
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Mulligan, Mark J., Stapleton, Jack T., Keitel, Wendy A., Frey, Sharon E., Chen, Wilbur H., Rouphael, Nadine, Edupuganti, Srilatha, Beck, Allison, Winokur, Patricia L., El Sahly, Hana M., Patel, Shital M., Atmar, Robert L., Graham, Irene, Anderson, Edwin, El-Kamary, Samer S., Pasetti, Marcela F., Sztein, Marcelo B., Hill, Heather, and Goll, Johannes B.
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TULAREMIA , *IMMUNOGLOBULINS , *FRANCISELLA tularensis , *RANDOMIZED controlled trials , *CLINICAL trials , *VACCINATION - Abstract
Background Tularemia is caused by Francisella tularensis , a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices. Methods A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180. Principal Results Both vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was −6.9% (−16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n = 98/104) for DVC-LVS and 94% (95% CI, 87, 97; n = 103/110) for USAMRIID-LVS (p = 1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p < 0.0001). Major conclusions The DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments. ClinicalTrials.gov identifier NCT01150695 [ABSTRACT FROM AUTHOR]
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- 2017
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190. Priming Vaccination With Influenza Virus H5 Hemagglutinin Antigen Significantly Increases the Duration of T cell Responses Induced by a Heterologous H5 Booster Vaccination.
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Hoft, Daniel F., Lottenbach, Kathleen, Goll, Johannes B., Hill, Heather, Winokur, Patricia L., Patel, Shital M., Brady, Rebecca C., Chen, Wilbur H., Edwards, Kathryn, Creech, C. Buddy, Frey, Sharon E., Blevins, Tamara P., Salomon, Rachelle, and Belshe, Robert B.
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VACCINATION , *IMMUNIZATION , *HEMAGGLUTININ , *AGGLUTININS , *HEMAGGLUTINATION tests - Abstract
Background: Influenza A(H5N1) virus and other avian influenza virus strains represent major pandemic threats. Like all influenza A virus strains, A(H5N1) viruses evolve rapidly. Innovative immunization strategies are needed to induce cross-protective immunity.Methods: Subjects primed with clade 1 H5 antigen, with or without adjuvant, and H5-naive individuals were boosted with clade 2 H5 antigen. The impact of priming on T cells capable of both proliferation and cytokine production after antigen restimulation was assessed.Results: Subjects previously vaccinated with clade 1 H5 antigen developed significantly enhanced clade 2 H5 cross-reactive T cell responses detectable 6 months after vaccination with clade 2 H5 antigen. Priming dose (15 µg vs 45 or 90 µg) had no effect on magnitude of heterotypic H5 T cell responses. In contrast, age at priming negatively modulated both the magnitude and duration of heterotypic H5 T cell responses. Elderly subjects developed significantly less heterotypic H5 T cell boosting, predominantly for T cells capable of cytokine production. Adjuvant had a positive albeit weaker effect than age. The magnitude of CD4(+) interferon-γ producing T cells correlated with H5 antibody responses.Conclusions: H5 heterotypic priming prior to onset of an A(H5N1) pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus. [ABSTRACT FROM AUTHOR]- Published
- 2016
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191. Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine.
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Mbawuike, Innocent N., Atmar, Robert L., Patel, Shital M., Corry, David B., Winokur, Patricia L., Brady, Rebecca C., Chen, Wilbur H., Edwards, Kathryn M., Creech, C. Buddy, Jr.Walter, Emmanuel B., Frey, Sharon E., Belshe, Robert B., Goll, Johannes B., Hill, Heather, and Keitel, Wendy A.
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H5N1 Influenza , *IMMUNE response , *GRANZYMES , *CYTOKINES , *CELLULAR immunity , *IMMUNOLOGICAL adjuvants , *VACCINATION - Abstract
Purpose The study aims were to determine whether inactivated influenza A/H5N1 vaccine administration elicited cell mediated immune (CMI) responses and the impact of adjuvant, vaccine dose and subject age on these responses. Methods Adults who were previously primed with either adjuvanted or unadjuvanted, inactivated, A/H5N1/Vietnam/1203/2004 (Clade 1) vaccine or unprimed (received placebo) in previous vaccine studies were randomized to receive one (primed) or two (unprimed) 15- or 90-mcg doses of inactivated, A/H5N1/Indonesia/05/05 (Clade 2) vaccine. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed from a subset of vaccinees to assess CMI responses using IFN-γ and granzyme B ELISPOT assays. Cytokine measurements were performed on PBMC supernatants after stimulation with H5N1 virus. Results PBMCs were available from 177 participants; 88 and 89 received 15-mcg and 90-mcg of unadjuvanted clade 2 vaccine, respectively. Following H5N1 clade 1 stimulation, IFN-γ but not granzyme B normalized spot-forming cell numbers had statistically significant increased numbers at each of the post-vaccination timepoints compared to baseline in pooled analyses of all vaccine doses and age groups. Clade 2 stimulation resulted in statistically significant increased numbers of IFN-γ cells only 180 days following the last vaccination. Responses were similar among younger and older study participants, as were responses among those primed with alum-adjuvanted or non-adjuvanted clade 1 H5N1 vaccines. The dosage of clade 2 vaccine did not impact CMI responses among primed subjects, but responses were statistically significantly greater in unprimed recipients of the 90-mcg dosage compared to unprimed recipients of the 15-mcg dosage. IFN-γ levels in the supernatants of stimulated PBMC were strongly correlated with IFN-γ ELISPOT results. Conclusion CMI responses occur in adults administered influenza A/H5N1 inactivated influenza vaccine. [ABSTRACT FROM AUTHOR]
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- 2016
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192. Norovirus Vaccine Against Experimental Human GII.4 Virus Illness: A Challenge Study in Healthy Adults.
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Bernstein, David I., Atmar, Robert L., Lyon, G. Marshall, Treanor, John J., Chen, Wilbur H., Jiang, Xi, Vinjé, Jan, Gregoricus, Nicole, Frenck, Robert W., Moe, Christine L., Al-Ibrahim, Mohamed S., Barrett, Jill, Ferreira, Jennifer, Estes, Mary K., Graham, David Y., Goodwin, Robert, Borkowski, Astrid, Clemens, Ralf, and Mendelman, Paul M.
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NOROVIRUSES , *VIRAL vaccines , *HEALTH of adults , *GASTROENTERITIS , *CLINICAL drug trials , *REVERSE transcriptase polymerase chain reaction , *PLACEBOS - Abstract
Background. Vaccines against norovirus, the leading cause of acute gastroenteritis, should protect against medically significant illness and reduce transmission.Methods. In this randomized, double-blind, placebo-controlled trial, 18- to 50-year-olds received 2 injections of placebo or norovirus GI.1/GII.4 bivalent vaccine-like particle (VLP) vaccine with 3-O-desacyl-4′-monophosphoryl lipid A (MPL) and alum. Participants were challenged as inpatients with GII.4 virus (4400 reverse transcription polymerase chain reaction [RT-PCR] units), and monitored for illness and infection.Results. Per protocol, 27 of 50 (54.0%) vaccinees and 30 of 48 (62.5%) controls were infected. Using predefined illness and infection definitions, vaccination did not meet the primary endpoint, but self-reported cases of severe (0% vaccinees vs 8.3% controls; P = .054), moderate or greater (6.0% vs 18.8%; P = .068), and mild or greater severity of vomiting and/or diarrhea (20.0% vs 37.5%; P = .074) were less frequent. Vaccination also reduced the modified Vesikari score from 7.3 to 4.5 (P = .002). Difficulties encountered were low norovirus disease rate, and inability to define illness by quantitative RT-PCR or further antibody rise in vaccinees due to high vaccine-induced titers. By day 10, 11 of 49 (22.4%) vaccinees were shedding virus compared with 17 of 47 (36.2%) placebo recipients (P = .179).Conclusions. Bivalent norovirus VLP vaccine reduced norovirus-related vomiting and/or diarrhea; field efficacy studies are planned.Clinical Trials Registration. NCT01609257. [ABSTRACT FROM AUTHOR]
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- 2015
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193. Robust mucosal-homing antibody-secreting B cell responses induced by intramuscular administration of adjuvanted bivalent human norovirus-like particle vaccine.
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Sundararajan, Aarthi, Sangster, Mark Y., Frey, Sharon, Atmar, Robert L., Chen, Wilbur H., Ferreira, Jennifer, Bargatze, Robert, Mendelman, Paul M., Treanor, John J., and Topham, David J.
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B cells , *INTRAMUSCULAR injections , *NOROVIRUSES , *VIRAL vaccines , *VIRAL antibodies , *FOODBORNE diseases - Abstract
Background Two major antigenically heterogenous norovirus genogroups (GI and GII) commonly infect humans and are the leading cause of foodborne, viral gastrointestinal infections in adults. Methods We assessed B cell responses in participants in a double-blind, placebo-controlled, dose-escalation phase 1 study of the safety and immunogenicity of an intramuscular bivalent norovirus virus-like particle (VLP) vaccine. The vaccine contained a GI.1 VLP (Norwalk) and a consensus GII.4 VLP, representing the two major genotypes that cause human disease, and was administered on days 0 and 28 to healthy adults aged 18–49 years. Four separate cohorts received increasing doses of 5 μg, 15 μg, 50 μg, and 150 μg of each VLP adjuvanted in monophosphoryl lipid A and alum. PBMCs were analyzed for B cell activation and mucosal homing markers (flow cytometry) and VLP-specific and total IgG and IgA Ab-secreting cells (ASCs); and serum titers of VLP-specific IgG, IgA, and Pan-Ig were determined. Results The vaccine elicited CD27+ CD38+ plasmablasts and high frequencies of ASCs specific for both VLP antigens in the peripheral blood at 7 days after the first dose. The plasmablasts exhibited a mucosal-homing phenotype and included a high proportion of IgA ASCs. Serum antibodies increased as early as 7 days after the first immunization. Conclusions The data suggest that a single dose of the IM bivalent norovirus vaccine is effective in activating pre-existing B cell memory. The rapid B cell response and the mucosal homing phenotype of induced ASCs are consistent with anamnestic responses in subjects primed by prior oral norovirus infection. This study is registered at ClinicalTrials.gov Identifier NCT01609257 . [ABSTRACT FROM AUTHOR]
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- 2015
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194. A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults.
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Treanor, John J, Atmar, Robert L, Frey, Sharon E, Gormley, Robert, Chen, Wilbur H, Ferreira, Jennifer, Goodwin, Robert, Borkowski, Astrid, Clemens, Ralf, and Mendelman, Paul M
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GASTROENTERITIS , *VIRAL vaccines , *IMMUNOGLOBULINS , *INTRAMUSCULAR injections , *RANDOMIZED controlled trials , *NOROVIRUS diseases , *BLIND experiment , *RESEARCH funding , *RNA viruses , *VIRAL antibodies , *LONGITUDINAL method - Abstract
Background: Noroviruses are the most important viral causes of gastroenteritis-related morbidity and mortality. A randomized, double-blind, placebo-controlled study evaluated an adjuvanted bivalent intramuscular norovirus virus-like particle (VLP) vaccine.Methods: Forty-eight adults aged 18-49 years received either 2 doses containing genotype GI.1 VLP and a consensus GII.4 VLP or 2 doses of placebo. Doses (5 µg, 15 µg, 50 µg, or 150 µg of each VLP) were administered 4 weeks apart in the first stage. Subsequently, 54 adults, aged 18-49 (n=16), 50-64 (n=19), and 65-85 (n=19) years, received 2 doses of vaccine containing 50 µg of each VLP. Total and class-specific antibody responses, as well as histoblood group antigen (HBGA) blocking antibody responses, were measured before and after each dose.Results: Local reactions were mainly injection site pain/tenderness, with no reported fever or vaccine-related serious adverse events. One dose of vaccine containing 50 µg of each VLP increased GI.1 geometric mean titers (GMTs) by 118-fold, 83-fold, and 24-fold and increased GII.4 GMTs by 49-fold, 25-fold, and 9-fold in subjects aged 18-49, 50-64, and 65-83 years, respectively. Serum antibody responses peaked at day 7 after the first dose, with no evidence of boosting following a second dose. Most subjects achieved HBGA-blocking antibody titers of ≥200.Conclusions: The vaccine was well tolerated and immunogenic. Rapid immune response to a single dose may be particularly useful in military personnel and travelers and in the control of outbreaks. Clinical Trials Registration. NCT01168401. [ABSTRACT FROM AUTHOR]- Published
- 2014
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195. Lower Antibody Levels to Staphylococcus aureus Exotoxins Are Associated With Sepsis in Hospitalized Adults With Invasive S. aureus Infections.
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Adhikari, Rajan P., Ajao, Adebola O., Aman, M. Javad, Karauzum, Hatice, Sarwar, Jawad, Lydecker, Alison D., Johnson, J. Kristie, Nguyen, Chinh, Chen, Wilbur H., and Roghmann, Mary-Claire
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STAPHYLOCOCCUS aureus , *EXOTOXIN , *STAPHYLOCOCCUS aureus infections , *SEPSIS , *BACTEREMIA - Abstract
Background. Staphylococcus aureus has numerous virulence factors, including exotoxins that may increase the severity of infection. This study was aimed at assessing whether preexisting antibodies to S. aureus toxins are associated with a lower risk of sepsis in adults with S. aureus infection complicated by bacteremia.Methods. We prospectively identified adults with S. aureus infection from 4 hospitals in Baltimore, MD, in 2009–2011. We obtained serum samples from prior to or at presentation of S. aureus bacteremia to measure total immunoglobulin G (IgG) and IgG antibody levels to 11 S. aureus exotoxins. Bacterial isolates were tested for the genes encoding S. aureus exotoxins using polymerase chain reaction (PCR).Results. One hundred eligible subjects were included and 27 of them developed sepsis. When adjusted for total IgG levels and stratified for the presence of toxin in the infecting isolate as appropriate, the risk of sepsis was significantly lower in those patients with higher levels of IgG against α-hemolysin (Hla), δ-hemolysin (Hld), Panton Valentine leukocidin (PVL), staphylococcal enterotoxin C-1 (SEC-1), and phenol-soluble modulin α3 (PSM-α3).Conclusions. Our results suggest that higher antibody levels against Hla, Hld, PVL, SEC-1, and PSM-α3 may protect against sepsis in patients with invasive S. aureus infections. [ABSTRACT FROM PUBLISHER]
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- 2012
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196. Adjuvanted Intranasal Norwalk Virus-Like Particle Vaccine Elicits Antibodies and Antibody-Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues.
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El-Kamary, Samer S., Pasetti, Marcela F., Mendelman, Paul M., Frey, Sharon E., Bernstein, David I., Treanor, John J., Ferreira, Jennifer, Chen, Wilbur H., Sublett, Richard, Richardson, Charles, Bargatze, Robert F., Sztein, Marcelo B., and Tacket, Carol O.
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IMMUNOGLOBULINS , *VACCINES , *NOROVIRUSES , *LIPIDS , *ANTIGENS - Abstract
Background. Noroviruses cause significant morbidity and mortality from acute gastroenteritis in all age groups worldwide. Methods. We conducted 2 phase 1 double-blind, controlled studies of a virus-like particle (VLP) vaccine derived from norovirus GI.1 genotype adjuvanted with monophosphoryl lipid A (MPL) and the mucoadherent chitosan. Healthy subjects 18-49 years of age were randomized to 2 doses of intranasal Norwalk VLP vaccine or controls 21 days apart. Study 1 evaluated 5-, 15-, and 50-μg dosages of Norwalk antigen, and study 2 evaluated 50- and 100-μg dosages. Volunteers recorded symptoms for 7 days after dosing, and safety was followed up for 180 days. Blood samples were collected for serological profile, antibody secreting cells (ASCs), and analysis of ASC homing receptors. Results. The most common symptoms were nasal stuffiness, discharge, and sneezing. No vaccine-related serious adverse events occurred. Norwalk VLP-specific immunoglobulin G and immunoglobulin A antibodies increased 4.8- and 9.1-fold, respectively, for the 100-μg dosage level. All subjects tested who received the 50- or 100-μg vaccine dose developed immunoglobulin A ASCs. These cells expressed molecules associated with homing to mucosal and peripheral lymphoid tissues. Conclusions. The intranasal monovalent adjuvanted Norwalk VLP vaccine was well tolerated and highly immunogenic and is a candidate for additional study. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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197. Use of Haemophilus influenzae Type b-Containing Vaccines Among American Indian and Alaska Native Infants: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.
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Collins JP, Loehr J, Chen WH, Clark M, Pinell-McNamara V, and McNamara LA
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- Humans, Infant, Advisory Committees, Centers for Disease Control and Prevention, U.S., Haemophilus influenzae type b immunology, Practice Guidelines as Topic, United States epidemiology, American Indian or Alaska Native, Haemophilus Infections prevention & control, Haemophilus Vaccines administration & dosage, Immunization Schedule
- Abstract
Invasive Haemophilus influenzae type b (Hib) disease is a serious bacterial infection that disproportionally affects American Indian and Alaska Native (AI/AN) populations. Hib vaccination with a monovalent Hib conjugate vaccine consisting of Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) conjugated to outer membrane protein complex of Neisseria meningitidis serogroup B, PRP-OMP (PedvaxHIB, Merck and Co., Inc.) has historically been preferred for AI/AN infants, who are at increased risk for invasive Hib disease, because it provides substantial protection after the first dose. On June 26, 2024, CDC's Advisory Committee on Immunization Practices (ACIP) recommended that a hexavalent, combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Hib conjugate, and hepatitis B (HepB) vaccine, DTaP-IPV-Hib-HepB (Vaxelis, MSP Vaccine Company) should be included with monovalent PRP-OMP in the preferential recommendation for AI/AN infants because of the PRP-OMP Hib component. A primary Hib vaccination series consisting of either 1) monovalent PRP-OMP (2-dose series at ages 2 and 4 months) or 2) DTaP-IPV-Hib-HepB (3-dose series at ages 2, 4, and 6 months) is preferred for AI/AN infants. DTaP-IPV-Hib-HepB is only indicated for use in infants at ages 2, 4, and 6 months and should not be used for the booster doses of Hib, DTaP, or IPV vaccines. For the booster dose of Hib vaccine, no vaccine formulation is preferred for AI/AN children; any Hib vaccine (except DTaP-IPV-Hib-HepB) should be used. This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of Hib-containing vaccines among AI/AN infants and children., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed by any authors.
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- 2024
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198. Safety and Tolerability of ShigActive™, a Shigella spp. Targeting Bacteriophage Preparation, in a Phase 1 Randomized, Double-Blind, Controlled Clinical Trial.
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Chen WH, Woolston J, Grant-Beurmann S, Robinson CK, Bansal G, Nkeze J, Permala-Booth J, Fraser CM, Tennant SM, Shriver MC, Pasetti MF, Liang Y, Kotloff KL, Sulakvelidze A, and Schwartz JA
- Abstract
Bacterial diseases of the gastrointestinal (GI) tract continue to be a major worldwide cause of human morbidity and mortality. Among various enteric pathogens, Shigella spp. are some of the most common and deadly bacterial pathogens. They are responsible for ~125 million worldwide cases of shigellosis, and ~14,000 deaths annually, the majority in children under the age of 5 and occurring in developing countries. Preventing and treating shigellosis with conventional drugs (e.g., vaccines and antibiotics) has proven to be very difficult. Here, we assessed the safety and tolerability of ShigActive™, a lytic bacteriophage preparation targeting Shigella spp., in a randomized, placebo-controlled, double-blind Phase 1 clinical trial. Ten participants randomized 4:1 received ShigActive™ or placebo co-administered with sodium bicarbonate orally three times daily for 7 days. Solicited and unsolicited adverse events (AEs) were observed for 29 days. Fifty percent of the subjects receiving ShigActive™ reported mild GI-related symptoms, while one participant experienced moderate fatigue. No serious or medically attended AEs occurred through day 90. Additionally, no significant differences in GI-associated inflammatory mediators or fecal microbiome changes were observed between placebo- and ShigActive™-treated subjects, or from a participants' baseline value. The results of this first-in-human (FIH) randomized, controlled Phase 1 trial of ShigActive™ demonstrate that it is safe and well tolerated when orally administered with no significant differences compared to placebo controls.
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- 2024
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199. How to develop a controlled human infection model for Clostridioides difficile.
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Hensen ADO, Vehreschild MJGT, Gerding DN, Krut O, Chen W, Young VB, Tzipori S, Solbach P, Gibani MM, Chiu C, de Keersmaecker SCJ, Dasyam D, Morel S, Devaster JM, Corti N, Kuijper EJ, Roestenberg M, and Smits WK
- Abstract
Background: Clostridioides difficile (C. difficile) remains the leading cause of healthcare-associated diarrhoea, posing treatment challenges because of antibiotic resistance and high relapse rates. Faecal microbiota transplantation is a novel treatment strategy to prevent relapses of C. difficile infection (CDI), however, the exact components conferring colonization resistance are unknown, hampering its translation to a medicinal product. The development of novel products independent of antibiotics, which increase colonization resistance or induce protective immune mechanisms is urgently needed., Objectives: To establish a framework for a Controlled Human Infection Model (CHIM) of C. difficile, in which healthy volunteers are exposed to toxigenic C. difficile spores, offering the possibility to test novel approaches and identify microbiota and immunological targets. Whereas experimental exposure to non-toxigenic C. difficile has been done before, a toxigenic C. difficile CHIM faces ethical, scientific, logistical, and biosafety challenges., Sources: Specific challenges in developing a C. difficile CHIM were discussed by a group of international experts during a workshop organized by Inno4Vac, an Innovative Health Initiative-funded consortium., Content: The experts agreed that the main challenges are: developing a clinically relevant CHIM that induces mild to moderate CDI symptoms but not severe CDI, determining the optimal C. difficile inoculum dose, and understanding the timing and duration of antibiotic pretreatment in inducing susceptibility to CDI in healthy volunteers., Implications: Should these challenges be tackled, a C. difficile CHIM will not only provide a way forward for the testing of novel products but also offer a framework for a better understanding of the pathophysiology, pathogenesis, and immunology of C. difficile colonization and infection., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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200. CountASAP: A Lightweight, Easy to Use Python Package for Processing ASAPseq Data.
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Boughter CT, Chatterjee B, Ohta Y, Gorga K, Blair C, Hill EM, Fasana Z, Adebamowo A, Ammar F, Kosik I, Murugan V, Chen WH, Singh NJ, and Meier-Schellersheim M
- Abstract
Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels. While software exists for the characterization of these datasets, there currently exists no tool explicitly designed to reformat ASAP surface marker FASTQ data into a count matrix which can then be used for these downstream analyses. To address this, we created CountASAP, an easy-to-use Python package purposefully designed to transform FASTQ files from ASAP experiments into count matrices compatible with commonly-used downstream bioinformatic analysis packages. CountASAP takes advantage of the independence of the relevant data structures to perform fully parallelized matches of each sequenced read to user-supplied input ASAP oligos and unique cell-identifier sequences., Competing Interests: Competing Interests The authors declare no competing interests.
- Published
- 2024
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