24 results on '"Christine M. Hay"'
Search Results
2. Human Disease Caused by Kalamiella piersonii
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Rodolfo Alpizar-Rivas, Andrew Cameron, and Christine M. Hay
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- 2022
3. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects.
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Richard N Greenberg, Christine M Hay, Jack T Stapleton, Thomas C Marbury, Eva Wagner, Eva Kreitmeir, Siegfried Röesch, Alfred von Krempelhuber, Philip Young, Richard Nichols, Thomas P Meyer, Darja Schmidt, Josef Weigl, Garth Virgin, Nathaly Arndtz-Wiedemann, and Paul Chaplin
- Subjects
Medicine ,Science - Abstract
BACKGROUND:Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. METHODS:MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. RESULTS:Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group MM were 804.1 and 605.8 for Group PM (with ratio of GMTs of 1.33 with 95% CI of [0.96, 1.84]). Similarly, GMTs measured by PRNT were 210.3 for Group MM and 126.7 for Group PM (with ratio 1.66 and 95% CI [0.95, 2.90]). CONCLUSIONS:One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. No cases of myopericarditis were observed following vaccinations with MVA. The safety, reactogenicity and immunogenicity were similar to that seen in younger (18-55 year old) healthy populations as investigated in other MVA trials. The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine. TRIAL REGISTRATION:ClinicalTrials.gov NCT00857493.
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- 2016
- Full Text
- View/download PDF
4. Pasteurella Endocarditis: A Case Report and Statistical Analysis of the Literature
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Christine M. Hay and Randall S. Porter
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0301 basic medicine ,medicine.medical_specialty ,animal diseases ,030106 microbiology ,Case Report ,Infectious and parasitic diseases ,RC109-216 ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Internal medicine ,medicine ,otorhinolaryngologic diseases ,Endocarditis ,030212 general & internal medicine ,Pasteurella ,Pasteurella multocida ,biology ,business.industry ,General Medicine ,Sulbactam ,respiratory system ,medicine.disease ,biology.organism_classification ,Metronidazole ,Cellulitis ,Daptomycin ,business ,medicine.drug - Abstract
Pasteurella is a genus of commensal bacteria of the oral cavity of several domesticated animals and a common cause of cellulitis after animal bites. Pasteurella has also been reported as a rare cause of endocarditis, with only 35 prior cases of definite Pasteurella endocarditis in the literature. Here, we present a case of Pasteurella multocida endocarditis treated successfully with surgery and antibiosis, as well as a review of the literature with statistical analysis of correlations between risk factors and clinical outcomes, as well as between treatment choices and clinical outcomes. Despite the small sample size, our analysis indicates a statistically significant correlation between comorbid liver disease and mortality, as well as a significant negative correlation between surgical treatment and mortality. This analysis implies a need for surgical management of endocarditis due to Pasteurella species and for more aggressive management of Pasteurella endocarditis in the setting of comorbid liver disease.
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- 2020
5. A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults.
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Michael C Keefer, Jill Gilmour, Peter Hayes, Dilbinder Gill, Jakub Kopycinski, Hannah Cheeseman, Michelle Cashin-Cox, Marloes Naarding, Lorna Clark, Natalia Fernandez, Catherine A Bunce, Christine M Hay, Sabrina Welsh, Wendy Komaroff, Lottie Hachaambwa, Tony Tarragona-Fiol, Eddy Sayeed, Devika Zachariah, James Ackland, Kelley Loughran, Burc Barin, Emmanuel Cormier, Josephine H Cox, Patricia Fast, and Jean-Louis Excler
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Medicine ,Science - Abstract
We conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (Ad35) vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN) and env (Ad35-ENV), both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults.Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions) or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively) within one of four dosage groups: Ad35-GRIN/ENV 2×10(9) (A), 2×10(10) (B), 2×10(11) (C), or Ad35-GRIN 1×10(10) (D) viral particles.No vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A-D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC) per 10(6) PBMC to any antigen was 78-139 across Groups A-C and 158-174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A-C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination.Ad35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second vaccination. T-cell responses were broad and polyfunctional.ClinicalTrials.gov NCT00851383.
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- 2012
- Full Text
- View/download PDF
6. Stopping Conventional Showering Decreases Pseudomonas Infections in left Ventricular Assist Device Patients
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Vakhtang Tchantchaleishvili, Nana Aburjania, Saadia Sherazi, Christine M. Hay, and Jeffrey D. Alexis
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Male ,medicine.medical_specialty ,Heart Ventricles ,medicine.medical_treatment ,Surgical Wound ,Biomedical Engineering ,Prosthesis Implantation ,Medicine (miscellaneous) ,Bioengineering ,030204 cardiovascular system & hematology ,Microbiology ,Biomaterials ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Surgical Wound Infection ,Pseudomonas Infections ,Retrospective Studies ,Postoperative Care ,business.industry ,Retrospective cohort study ,Surgical wound ,General Medicine ,Middle Aged ,Surgery ,030228 respiratory system ,Ventricular assist device ,Female ,Heart-Assist Devices ,business - Abstract
Background Left ventricular assist device (LVAD) exit-site infections represent a major challenge in the era of modern LVADs. Infections caused by Pseudomonas are particularly difficult to treat due to limited antibiotic susceptibility. We hypothesized that keeping the LVAD exit site dry while bathing could result in reduced incidence of Pseudomonas infections. Methods Starting in April 2013, all patients who underwent placement of HeartMate II (HM II) LVAD were instructed not to take conventional showers and to keep the exit site dry while bathing. We retrospectively reviewed patients who underwent HeartMate II LVAD implantation at our institution. Overall and Pseudomonas exit-site infections were compared between two groups: Group 1 was implanted with an LVAD prior to intervention (4/1/2013) and Group 2 after the intervention. Both groups were subjected to cumulative hazard analysis and compared using log-rank test. Results From November 2006 to September 2015, 283 patients underwent HM II LVAD placement at a single institution (Group 1, 163 patients; Group 2, 120 patients). Median age was 59 years (interquartile range [IQR] 50–65), and 57 (20%) were female. Overall, driveline infection was noted in 86 (30%) patients. Pseudomonas was the causative or coexisting organism in 16 (6%) patients. Median days to infection were 347 (IQR, 162–568). Driveline infection was identified in 69 (42%) patients in Group 1 and 17 (14 %) in Group 2. Pseudomonas was an infectious organism in 15 (9%) patients of Group 1 and one (1%) patient of Group 2. The incidence of Pseudomonas exit-site infections (p = 0.077) decreased substantially after the intervention. Conclusions Stopping conventional showering may reduce the rate of Pseudomonas LVAD exit-site infections. Additional, multi-institutional data are needed to further evaluate these findings.
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- 2017
7. Continuous-flow left ventricular assist device systems infections: current outcomes and management strategies
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Nana Aburjania, Muhammad R Sohail, and Christine M. Hay
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Keynote Lecture Series ,medicine.medical_specialty ,business.industry ,Continuous flow ,medicine.medical_treatment ,equipment and supplies ,medicine.disease ,Diagnostic modalities ,Clinical trial ,Ventricular assist device ,Heart failure ,medicine ,Materials Chemistry ,Surgery ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business - Abstract
Left ventricular assisted devices (LVADs) are increasingly used for management of patients with advanced heart failure. However, infection remains one of the most commonly reported complications. Diagnosis, as well as treatment of LVAD infections is challenging. There are multiple diagnostic modalities that have been used to assist with accurate diagnosis of LVAD infections. Treatment of the infection can be especially challenging in these patients, given the presence of the implantable device that cannot be easily replaced or removed. There are no clinical trials assessing the best approach to diagnosis, treatment or long-term management of LVAD infections. In this article we review the most recent diagnostic modalities and treatment approaches, as well as offer our guidance on diagnosis and treatment of LVAD infections.
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- 2021
8. DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8 + T-Cell Responses by Interleukin-12 Plasmid DNA
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Rong Xu, Kristen W. Cohen, John H. Eldridge, Nidhi Kochar, Georgia D. Tomaras, Ian Frank, Michael A. Egan, M. Juliana McElrath, Drew Hannaman, Daryl E. Morris, Christine M. Hay, Ayuko Ota-Setlik, Raphael Gottardo, Nicole Frahm, Magdalena E. Sobieszczyk, Shuying S. Li, Mary Allen, Lawrence Corey, David K. Clarke, Stephen C. De Rosa, Hong Van Tieu, Gregory J. Wilson, Greg Finak, Peter B. Gilbert, and Marnie Elizaga
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0301 basic medicine ,Microbiology (medical) ,biology ,business.industry ,Electroporation ,Immunogenicity ,medicine.medical_treatment ,Clinical Biochemistry ,Immunology ,Vaccine trial ,biology.organism_classification ,Virology ,DNA vaccination ,Vaccination ,03 medical and health sciences ,030104 developmental biology ,Vesicular stomatitis virus ,Immunology and Allergy ,Medicine ,HIV vaccine ,business ,Adjuvant - Abstract
The HIV Vaccine Trials Network (HVTN) 087 vaccine trial assessed the effect of increasing doses of pIL-12 (interleukin-12 delivered as plasmid DNA) adjuvant on the immunogenicity of an HIV-1 multiantigen (MAG) DNA vaccine delivered by electroporation and boosted with a vaccine comprising an attenuated vesicular stomatitis virus expressing HIV-1 Gag (VSV-Gag). We randomized 100 healthy adults to receive placebo or 3 mg HIV-MAG DNA vaccine (ProfectusVax HIV-1 gag / pol or ProfectusVax nef / tat / vif , env ) coadministered with pIL-12 at 0, 250, 1,000, or 1,500 μg intramuscularly by electroporation at 0, 1, and 3 months followed by intramuscular inoculation with 3.4 × 10 7 PFU VSV-Gag vaccine at 6 months. Immune responses were assessed after the prime and boost and 6 months after the last vaccination. High-dose pIL-12 increased the magnitude of CD8 + T-cell responses postboost compared to no pIL-12 ( P = 0.02), while CD4 + T-cell responses after the prime were higher in the absence of pIL-12 than with low- and medium-dose pIL-12 ( P ≤ 0.05). The VSV boost increased Gag-specific CD4 + and CD8 + T-cell responses in all groups ( P < 0.001 for CD4 + T cells), inducing a median of four Gag epitopes in responders. Six to 9 months after the boost, responses decreased in magnitude, but CD8 + T-cell response rates were maintained. The addition of a DNA prime dramatically improved responses to the VSV vaccine tested previously in the HVTN 090 trial, leading to broad epitope targeting and maintained CD8 + T-cell response rates at early memory. The addition of high-dose pIL-12 given with a DNA prime by electroporation and boosted with VSV-Gag increased the CD8 + T-cell responses but decreased the CD4 + responses. This approach may be advantageous in reshaping the T-cell responses to a variety of chronic infections or tumors. (This study has been registered at ClinicalTrials.gov under registration no. NCT01578889.)
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- 2017
9. DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8
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Shuying S, Li, Nidhi K, Kochar, Marnie, Elizaga, Christine M, Hay, Gregory J, Wilson, Kristen W, Cohen, Stephen C, De Rosa, Rong, Xu, Ayuko, Ota-Setlik, Daryl, Morris, Greg, Finak, Mary, Allen, Hong-Van, Tieu, Ian, Frank, Magdalena E, Sobieszczyk, Drew, Hannaman, Raphael, Gottardo, Peter B, Gilbert, Georgia D, Tomaras, Lawrence, Corey, David K, Clarke, Michael A, Egan, John H, Eldridge, M Juliana, McElrath, and Nicole, Frahm
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AIDS Vaccines ,Adult ,Male ,Vaccines ,viruses ,Genetic Vectors ,Vaccination ,Immunization, Secondary ,HIV Infections ,CD8-Positive T-Lymphocytes ,Middle Aged ,Interleukin-12 ,gag Gene Products, Human Immunodeficiency Virus ,Vesicular stomatitis Indiana virus ,Young Adult ,Immunogenicity, Vaccine ,Adjuvants, Immunologic ,HIV-1 ,Vaccines, DNA ,Humans ,Female ,Epitope Mapping ,Plasmids - Abstract
The HIV Vaccine Trials Network (HVTN) 087 vaccine trial assessed the effect of increasing doses of pIL-12 (interleukin-12 delivered as plasmid DNA) adjuvant on the immunogenicity of an HIV-1 multiantigen (MAG) DNA vaccine delivered by electroporation and boosted with a vaccine comprising an attenuated vesicular stomatitis virus expressing HIV-1 Gag (VSV-Gag). We randomized 100 healthy adults to receive placebo or 3 mg HIV-MAG DNA vaccine (ProfectusVax HIV-1 gag/pol or ProfectusVax nef/tat/vif, env) coadministered with pIL-12 at 0, 250, 1,000, or 1,500 μg intramuscularly by electroporation at 0, 1, and 3 months followed by intramuscular inoculation with 3.4 × 107 PFU VSV-Gag vaccine at 6 months. Immune responses were assessed after the prime and boost and 6 months after the last vaccination. High-dose pIL-12 increased the magnitude of CD8+ T-cell responses postboost compared to no pIL-12 (P = 0.02), while CD4+ T-cell responses after the prime were higher in the absence of pIL-12 than with low- and medium-dose pIL-12 (P ≤ 0.05). The VSV boost increased Gag-specific CD4+ and CD8+ T-cell responses in all groups (P < 0.001 for CD4+ T cells), inducing a median of four Gag epitopes in responders. Six to 9 months after the boost, responses decreased in magnitude, but CD8+ T-cell response rates were maintained. The addition of a DNA prime dramatically improved responses to the VSV vaccine tested previously in the HVTN 090 trial, leading to broad epitope targeting and maintained CD8+ T-cell response rates at early memory. The addition of high-dose pIL-12 given with a DNA prime by electroporation and boosted with VSV-Gag increased the CD8+ T-cell responses but decreased the CD4+ responses. This approach may be advantageous in reshaping the T-cell responses to a variety of chronic infections or tumors. (This study has been registered at ClinicalTrials.gov under registration no. NCT01578889.)
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- 2017
10. Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults
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Xuesong Yu, Peter B. Gilbert, Lindsey R. Baden, Georgia D. Tomaras, Paul A. Goepfert, Yunda Huang, David C. Montefiori, M. Juliana McElrath, Nicole Frahm, Christine M. Hay, M. Anthony Moody, Susan Buchbinder, Harriet L. Robinson, Kelly E. Seaton, Guido Ferrari, Nicole Grunenberg, and Brittany J. Sanchez
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RNA viruses ,Male ,0301 basic medicine ,Modified vaccinia Ankara ,Physiology ,viruses ,Antibody Response ,lcsh:Medicine ,HIV Antibodies ,Pathology and Laboratory Medicine ,Biochemistry ,White Blood Cells ,0302 clinical medicine ,Immunodeficiency Viruses ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,Vaccines, DNA ,Medicine ,Public and Occupational Health ,030212 general & internal medicine ,HIV vaccine ,lcsh:Science ,Immune Response ,AIDS Vaccines ,Vaccines ,Immune System Proteins ,Multidisciplinary ,biology ,T Cells ,Viral Vaccine ,Immunogenicity ,Vaccination ,Middle Aged ,Vaccination and Immunization ,3. Good health ,Infectious Diseases ,Medical Microbiology ,Viral Pathogens ,Viruses ,Female ,Pathogens ,Cellular Types ,Antibody ,Research Article ,Adult ,Infectious Disease Control ,Adolescent ,Immune Cells ,Immunology ,Microbiology ,Antibodies ,Young Adult ,03 medical and health sciences ,Double-Blind Method ,Antigen ,Virology ,Retroviruses ,Humans ,Avidity ,Microbial Pathogens ,Blood Cells ,Viral vaccines ,business.industry ,Lentivirus ,lcsh:R ,Organisms ,HIV vaccines ,Biology and Life Sciences ,Proteins ,HIV ,Granulocyte-Macrophage Colony-Stimulating Factor ,Cell Biology ,030104 developmental biology ,HIV-1 ,biology.protein ,lcsh:Q ,Preventive Medicine ,business - Abstract
BACKGROUNDA phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env.METHODSFour US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively. Peak immunogenicity was measured 2 weeks post-last vaccination.RESULTSAll regimens were well tolerated and safe. Full dose DgDgM_M and DgDgMM_M regimens generated Env-specific IgG to HIV-1 Env in >90%, IgG3 in >80%, and IgA in CONCLUSIONThis DNA/MVA prime-boost regimen induced durable, functional humoral responses that included ADCC, high antibody avidity, and Env IgG1 and IgG3 binding responses to the immunodominant region of gp41. The third, spaced MVA boost improved the overall quality of the antibody response. These products without co-expressed GM-CSF but combined with protein boosts will be considered for efficacy evaluation.TRIAL REGISTRATIONClinicalTrials.gov NCT01571960.
- Published
- 2017
11. DNA and Modified Vaccinia Virus Ankara Vaccines Encoding Multiple Cytotoxic and Helper T-Lymphocyte Epitopes of Human Immunodeficiency Virus Type 1 (HIV-1) Are Safe but Weakly Immunogenic in HIV-1-Uninfected, Vaccinia Virus-Naive Adults
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Stephen C. De Rosa, Farah L. Cassis-Ghavami, Spyros A. Kalams, Geoffrey J. Gorse, Christine M. Hay, Brian D. Livingston, Elizabeth A. Noonan, Mark Newman, Jonathan D. Fuchs, and Allan C. deCamp
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Adult ,Male ,Microbiology (medical) ,Adolescent ,Helper T lymphocyte ,T-Lymphocytes ,viruses ,Genetic Vectors ,Clinical Biochemistry ,Immunology ,Epitopes, T-Lymphocyte ,Vaccinia virus ,Biology ,complex mixtures ,Virus ,Epitope ,Placebos ,Interferon-gamma ,Young Adult ,chemistry.chemical_compound ,Immune system ,Double-Blind Method ,Vaccines, DNA ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,AIDS Vaccines ,Vaccines ,Perforin ,Tumor Necrosis Factor-alpha ,Viral Vaccine ,Viral Vaccines ,Virology ,chemistry ,HIV-1 ,Interleukin-2 ,Female ,Vaccinia - Abstract
We evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or gamma interferon production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses, including the production of tumor necrosis factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe but were ineffective at inducing HIV-1-specific immune responses and induced much weaker responses than MVA vaccines expressing the entire open reading frames of HIV-1 proteins.
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- 2012
12. Comparison of the immunogenicity and safety of a split-virion, inactivated, trivalent influenza vaccine (Fluzone®) administered by intradermal and intramuscular route in healthy adults
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Kathryn M. Edwards, Mark Wolff, Rebecca C. Brady, Robert W. Frenck, Thomas R. Cate, Robert B. Belshe, John J. Treanor, James D. Campbell, Christine M. Hay, Cornelia L. Dekker, Heather Hill, Patricia L. Winokur, Nadia Tornieporth, Tom LeDuc, and Emmanuel B. Walter
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Adult ,Male ,Trivalent influenza vaccine ,Injections, Intradermal ,Influenza vaccine ,Antibodies, Viral ,medicine.disease_cause ,Injections, Intramuscular ,Article ,Influenza A Virus, H1N1 Subtype ,Influenza, Human ,Influenza A virus ,Humans ,Medicine ,Pain Measurement ,Hemagglutination assay ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Influenza A Virus, H3N2 Subtype ,Immunogenicity ,Vaccination ,Public Health, Environmental and Occupational Health ,Hemagglutination Inhibition Tests ,Middle Aged ,Titer ,Infectious Diseases ,Immunization ,Influenza Vaccines ,Antibody Formation ,Immunology ,Molecular Medicine ,Female ,business - Abstract
The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system, (BD Soluvia™ Microinjection Systema), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years, [N=814] and 50-64 years, [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6 μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard IM TIV. Local erythema and swelling were significantly more common in the ID groups but the reactions were mild to moderate and short-lived. No significant safety issues related to intradermal administration were identified. Participants given TIV ID provided favorable responses to questions about their experiences with ID administration. In conclusion, for the aggregated cohorts of adults 18 to 64 years of age, reduced doses (6 μg and 9 μg) of TIV delivered ID using a novel microinjection system stimulated comparable HAI antibody responses to standard TIV given IM. The reduced 3 μg dose administered ID by needle and syringe, as well as the 6 μg ID for subjects aged 50-64 years of age generated poorer immune responses as compared to the 15 μg IM dose.
- Published
- 2011
13. Phase 1 Safety and Immunogenicity Testing of DNA and Recombinant Modified Vaccinia Ankara Vaccines Expressing HIV-1 Virus-like Particles
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Stephen C. DeRosa, Alicia Sato, Lindsey R. Baden, Georgia D. Tomaras, Paul A. Goepfert, Olivier D. Defawe, Marnie Elizaga, Linda S. Wyatt, Lilin Lai, William A. Blattner, Sharon E. Frey, Bernard Moss, Harriet L. Robinson, Massimo Cardinali, Li Qin, David C. Montefiori, Christine M. Hay, Spyros A. Kalams, Yongxian Xu, and John Hural
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Modified vaccinia Ankara ,Adolescent ,viruses ,T cell ,Genetic Vectors ,Enzyme-Linked Immunosorbent Assay ,HIV Infections ,Vaccinia virus ,CD8-Positive T-Lymphocytes ,HIV Antibodies ,Biology ,complex mixtures ,Drug Administration Schedule ,Virus ,DNA vaccination ,law.invention ,Placebos ,Major Articles and Brief Reports ,Young Adult ,chemistry.chemical_compound ,Double-Blind Method ,law ,Vaccines, DNA ,medicine ,Humans ,Immunology and Allergy ,AIDS Vaccines ,Immunogenicity ,Middle Aged ,Virology ,United States ,CD4 Lymphocyte Count ,Infectious Diseases ,medicine.anatomical_structure ,chemistry ,Immunology ,HIV-1 ,Recombinant DNA ,Female ,Vaccinia - Abstract
Background. Recombinant DNA and modified vaccinia virus Ankara (rMVA) vaccines represent a promising approach to an HIV/AIDS vaccine. This Phase 1 clinical trial compared the safety and immunogenicity of a rMVA vaccine administered with and without DNA vaccine priming Methods. GeoVax pGA2/JS7 DNA (D) and MVA/HIV62 (M) vaccines encode noninfectious virus-like particles. Intramuscular needle injections were used to deliver placebo, 2 doses of DNA followed by 2 doses of rMVA (DDMM), one dose of DNA followed by 2 doses of rMVA (DMM), or 3 doses of rMVA (MMM) to HIV-seronegative participants. Results. Local and systemic symptoms were mild or moderate. Immune response rates for CD4 + and CD8 + T cells were highest in the DDMM group and lowest in the MMM group (77% vs 43% CD4 + and 42% vs 17% CD8 +). In contrast, response rates for Env binding and neutralizing Ab were highest in the MMM group. The DMM group had intermediate response rates. A 1/10th-dose DDMM regimen induced similar T cell but reduced Ab response rates compared with the full-dose DDMM. Conclusions. MVA62 was well tolerated and elicited different patterns of T cell and Ab responses when administered alone or in combination with the JS7 DNA vaccine.
- Published
- 2011
14. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects
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Siegfried Roesch, Eva Kreitmeir, Darja Schmidt, Richard A. Nichols, Garth Virgin, Richard N. Greenberg, Philip M. Young, Christine M. Hay, Alfred von Krempelhuber, Thomas Meyer, Eva Wagner, Paul Chaplin, Josef Weigl, Nathaly Arndtz-Wiedemann, Thomas C. Marbury, and Jack T. Stapleton
- Subjects
0301 basic medicine ,Male ,Modified vaccinia Ankara ,Viral Diseases ,Physiology ,viruses ,lcsh:Medicine ,Viral Plaque Assay ,Smallpox Virus ,Pathology and Laboratory Medicine ,Biochemistry ,Placebos ,0302 clinical medicine ,Immune Physiology ,Vaccines, DNA ,Medicine and Health Sciences ,Public and Occupational Health ,030212 general & internal medicine ,Enzyme-Linked Immunoassays ,lcsh:Science ,Smallpox vaccine ,Booster Doses ,Aged, 80 and over ,education.field_of_study ,Vaccines ,Multidisciplinary ,Immune System Proteins ,Immunogenicity ,Viral Vaccine ,Poxviruses ,Middle Aged ,Vaccination and Immunization ,3. Good health ,Vaccination ,Infectious Diseases ,Bioassays and Physiological Analysis ,Seroconversion ,Medical Microbiology ,Viral Pathogens ,Viruses ,Female ,Pathogens ,Smallpox Vaccine ,Research Article ,medicine.medical_specialty ,Population ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Research and Analysis Methods ,complex mixtures ,Microbiology ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Antigens ,education ,Immunoassays ,Microbial Pathogens ,Demography ,Enzyme Assays ,Reactogenicity ,business.industry ,lcsh:R ,Organisms ,Biology and Life Sciences ,Proteins ,Viral Vaccines ,Virology ,030104 developmental biology ,Immunologic Techniques ,lcsh:Q ,Preventive Medicine ,business ,DNA viruses ,Biochemical Analysis ,Smallpox - Abstract
Background Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. Methods MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Results Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group MM were 804.1 and 605.8 for Group PM (with ratio of GMTs of 1.33 with 95% CI of [0.96, 1.84]). Similarly, GMTs measured by PRNT were 210.3 for Group MM and 126.7 for Group PM (with ratio 1.66 and 95% CI [0.95, 2.90]). Conclusions One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. No cases of myopericarditis were observed following vaccinations with MVA. The safety, reactogenicity and immunogenicity were similar to that seen in younger (18-55 year old) healthy populations as investigated in other MVA trials. The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine. Trial registration ClinicalTrials.gov NCT00857493.
- Published
- 2015
15. Lack of Viral Escape and Defective In Vivo Activation of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes in Rapidly Progressive Infection
- Author
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Steven M. Wolinsky, Maria Pia DePasquale, Richard T. D'Aquila, Bruce D. Walker, Debbie J. Ruhl, John M. Crawford, Nesli Basgoz, David C. Montefiori, James M. Billingsley, Cara C. Wilson, and Christine M. Hay
- Subjects
Adult ,Male ,Time Factors ,Immunology ,Epitopes, T-Lymphocyte ,Gene Products, gag ,HIV Infections ,chemical and pharmacologic phenomena ,Viremia ,Lymphocyte proliferation ,HIV Antibodies ,Lymphocyte Activation ,Major histocompatibility complex ,Microbiology ,Epitope ,Major Histocompatibility Complex ,Fatal Outcome ,Immune system ,Neutralization Tests ,Virology ,HLA-A2 Antigen ,medicine ,Humans ,Cytotoxic T cell ,Longitudinal Studies ,Lymphocytes ,biology ,medicine.disease ,CTL ,Phenotype ,Insect Science ,Mutation ,Disease Progression ,HIV-1 ,biology.protein ,Pathogenesis and Immunity ,Antibody ,Peptides ,Immunologic Memory ,Cell Division ,T-Lymphocytes, Cytotoxic - Abstract
Human immunodeficiency virus type 1 (HIV-1)-specific immune responses over the course of rapidly progressive infection are not well defined. Detailed longitudinal analyses of neutralizing antibodies, lymphocyte proliferation, in vivo-activated and memory cytotoxic T-lymphocyte (CTL) responses, and viral sequence variation were performed on a patient who presented with acute HIV-1 infection, developed an AIDS-defining illness 13 months later, and died 45 months after presentation. Neutralizing-antibody responses remained weak throughout, and no HIV-1-specific lymphocyte proliferative responses were seen even early in the disease course. Strong in vivo-activated CTL directed against Env and Pol epitopes were present at the time of the initial drop in viremia but were quickly lost. Memory CTL against Env and Pol epitopes were detected throughout the course of infection; however, these CTL were not activated in vivo. Despite an initially narrow CTL response, new epitopes were not targeted as the disease progressed. Viral sequencing showed the emergence of variants within the two targeted CTL epitopes; however, viral variants within the immunodominant Env epitope were well recognized by CTL, and there was no evidence of viral escape from immune system detection within this epitope. These data demonstrate a narrowly directed, static CTL response in a patient with rapidly progressive disease. We also show that disease progression can occur in the presence of persistent memory CTL recognition of autologous epitopes and in the absence of detectable escape from CTL responses, consistent with an in vivo defect in activation of CTL.
- Published
- 1999
16. Safety and Immunogenicity of IMVAMUNE® Smallpox Vaccine Using Different Strategies for a Post Event Scenario
- Author
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Heather Hill, Patricia L. Winokur, Robert A. Salata, Robert B. Belshe, Sharon E. Frey, Ying Zhang, Samer S. El-Kamary, Christine B. Turley, Christine M. Hay, Frances K. Newman, Paul Chaplin, Magdalena Tary-Lehmann, and Emmanuel B. Walter
- Subjects
Adult ,Male ,Modified vaccinia Ankara ,medicine.medical_specialty ,Adolescent ,Enzyme-Linked Immunosorbent Assay ,Placebo ,Antibodies, Viral ,Vaccines, Attenuated ,Article ,Young Adult ,Internal medicine ,medicine ,Humans ,Smallpox vaccine ,Immunity, Cellular ,Reactogenicity ,General Veterinary ,General Immunology and Microbiology ,business.industry ,ELISPOT ,Immunogenicity ,Vaccination ,Public Health, Environmental and Occupational Health ,Antibody titer ,Variola virus ,Antibodies, Neutralizing ,Bioterrorism ,Infectious Diseases ,Immunology ,Antibody Formation ,Molecular Medicine ,Female ,business ,Smallpox Vaccine ,Smallpox - Abstract
Introduction Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE® (modified vaccinia Ankara vaccine against smallpox) was compared to the currently recommended 0- and 28-day schedule for non-inferiority by evaluating the magnitude and kinetics of the immune responses. Methods Subjects were assigned to receive IMVAMUNE or placebo administered subcutaneously on Days 0 and 7, Days 0 and 28, or Day 0. Blood was collected for antibody and cell-mediated immune assays. Subjects were followed for safety for 12 months after last vaccination. Results The primary endpoint of this study was the geometric mean antibody titers (GMT) at 14 days post last vaccination. Of 208 subjects enrolled, 191 received vaccine (Group: 0 + 7, Group: 0 + 28 and Group: 0) and 17 received placebo. Moderate/severe systemic reactogenicity after any vaccination were reported by 31.1%, 25.4%, and 28.6% of the subjects for Group: 0 + 7, Group: 0 + 28, and Group: 0, respectively (Chi-square test, P = 0.77). Based on BN's Plaque Reduction Assay GMTs, Group: 0 + 7 was non-inferior to Group: 0 + 28 at Day 4, 180, and 365 after the second vaccination. On Day 14, Group: 0 + 7 and Group: 0 + 28 GMT were 10.8 (CI: 9.0, 12.9) and 30.2 (CI: 22.1, 41.1), respectively. Based on BN's Enzyme-linked immunosorbent assay, the proportion of subjects with positive titers for Group: 0 + 28 was significantly greater than that for Group: 0 + 7 after second vaccination at Days 4 and 180. By Day 14 after the second dose, the IFN-γ enzyme-linked immunosorbent spot (ELISPOT) responses were similar for Group: 0 + 28 and Group: 0 + 7. Conclusion Overall, a standard dose of IMVAMUNE (0.5 mL of 1 x 108 TCID/mL) administered subcutaneously was safe and well tolerated. A second dose of IMVAMUNE at Day 28 compared to Day 7 provided greater antibody responses and the maximal number of responders. By Day 14 after the second dose, IFN-γ ELISPOT responses were similar for Group: 0 + 28 and Group: 0 + 7.
- Published
- 2013
17. Stopping Conventional Showering Decreases Pseudomonas Exit Site Infections in Left Ventricular Assist Device Patients
- Author
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Saadia Sherazi, Vakhtang Tchantchaleishvili, Jeffrey D. Alexis, Nana Aburjania, and Christine M. Hay
- Subjects
Pulmonary and Respiratory Medicine ,Exit site ,Transplantation ,medicine.medical_specialty ,business.industry ,Ventricular assist device ,medicine.medical_treatment ,medicine ,Surgery ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business - Published
- 2016
18. Safety and immunogenicity of a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125) in healthy young adults
- Author
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John J. Treanor, David N. Taylor, Langzhou Song, Alan Shaw, Christine M. Hay, Lynda Tussey, Ge Liu, Theresa Fitzgerald, Uma Kavita, Carrie Nolan, and Irving Dark
- Subjects
Adult ,Male ,Adolescent ,Influenza vaccine ,Gene Expression ,Hemagglutinins, Viral ,Antibodies, Viral ,Injections, Intramuscular ,Placebos ,Young Adult ,Antigen ,Neutralization Tests ,Escherichia coli ,Medicine ,Humans ,Adverse effect ,Vaccines, Synthetic ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Immunogenicity ,Vaccination ,Public Health, Environmental and Occupational Health ,Hemagglutination Inhibition Tests ,Middle Aged ,Antibodies, Bacterial ,Infectious Diseases ,C-Reactive Protein ,TLR5 ,Influenza Vaccines ,Immunology ,biology.protein ,Molecular Medicine ,Cytokines ,Female ,Antibody ,business ,Flagellin - Abstract
Background The need for worldwide seasonal and pandemic vaccine production has increased interest in the development of innovative technologies for influenza vaccine production. We evaluated a novel influenza vaccine consisting of the globular head of the HA1 domain of the A/Solomon Islands/3/2006 (H1N1) influenza virus (VAX125) genetically fused to the TLR5 ligand, flagellin, and produced in E. coli. Methods 128 healthy adult subjects 18–49 years old were enrolled in a clinical trial conducted in three stages at a single center. Stage 1 was an open-label, dose escalation study in which the VAX125 vaccine was administered intramuscularly (im) at doses of 0.1 μg, 0.3 μg, 1 μg, 2 μg, 3 μg, 5 μg and 8 μg to groups of 8 subjects each. Stage 2 was a double-blind, placebo-controlled study in which subjects were randomized to receive 1.0 μg and 2.0 μg VAX125 vaccine doses or placebo, with 16 subjects per group. Finally, an additional 24 subjects received a 0.5 μg dose of VAX125 in stage 3, which was a non-randomized, open label study. In all parts subjects were followed for adverse events and sera was tested by hemagglutination-inhibition (HAI) and microneutralization (MN) against egg-grown virus on days 0, 7, 14, and 28. Serum C-reactive protein (CRP), cytokine levels, and anti-flagellin antibody were also assessed. Results Vaccine was generally well tolerated and there were no serious adverse events. Pain at the injection site was the most common local adverse event, and was mild or moderate in intensity. Systemic symptoms after vaccination include fatigue and headache, and two subjects, who received either 3 or 8 μg, had moderately severe systemic symptoms accompanied by substantial increases in serum CRP. Serum antibody responses against SI were seen by HAI and MN in most study subjects, with the geometric mean titer of post vaccination antibody increasing in a dose-dependent fashion. Overall, four-fold or greater serum HAI responses were seen in 61 of 96 (64%) subjects who received doses of 0.5 μg or greater, including in 46 of 72 subjects who received doses from 0.5 μg to 2 μg. Conclusions The globular head of the influenza HA expressed in a prokaryotic system was able to induce a functional antibody response against native virions. Vigorous responses were seen at relatively low doses of HA antigen suggesting that the addition of flagellin provided a substantial adjuvanting effect. The high levels of immune response at low doses of antigen and the relative ease of production associated with E. coli expression suggests that this approach may represent an effective strategy for enhancing the global influenza vaccine supply.
- Published
- 2010
19. P19-58 LB. Comparison of the immunogenicity in humans and rhesus macaques of vaccines consisting of DNA priming and MVA boosting and MVA priming and boosting
- Author
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Lilin Lai, Harriet L. Robinson, Christine M. Hay, Georgia D. Tomaras, Paul A. Goepfert, Bernard Moss, Alicia Sato, S De Rosa, Li Qin, Olivier D. Defawe, Rama Rao Amara, Y Xu, and Linda S. Wyatt
- Subjects
Vaccine research ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,business.industry ,Immunogenicity ,Infectious Diseases ,Virology ,Family medicine ,Poster Presentation ,Immunology ,medicine ,University medical ,business ,lcsh:RC581-607 - Abstract
Address: 1GeoVax Inc., Atlanta, GA, USA, 2Yerkes National Primate Research Center and Emory Vaccine Center, Atlanta, GA, USA, 3Fred Hutchinson Cancer Research Center, HVTN Laboratory Program, Seattle, WA, USA, 4Duke University Medical Center, Durham, NC, USA, 5Fred Hutchinson Cancer Research Center, HVTN SCHARP, Seattle, WA, USA, 6National Institutes of Health, Bethesda, MD, USA, 7National Institutes of Health, NIAID, Bethesda, MD, USA, 8University of Rochester, Rochester, NY, USA and 9University of Alabama at Birmingham, Alabama Vaccine Research Clinic, Birmingham, AL, USA * Corresponding author
- Published
- 2009
20. Central-Line Associated Bloodstream Infections Related to Inpatient Pulmonary Artery Catheterization Among Patients Waiting for Heart Transplantation
- Author
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Usama A. Daimee, Jeffrey D. Alexis, Saadia Sherazi, Katherine S. Dodd, Eugene Storozynsky, Christine M. Hay, Leway Chen, and Lynn Fine
- Subjects
Heart transplantation ,medicine.medical_specialty ,Central line ,business.industry ,medicine.medical_treatment ,Internal medicine ,medicine.artery ,Pulmonary artery ,Cardiology ,Medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2015
21. Combination therapy with polymyxin B for the treatment of multidrug-resistant Gram-negative respiratory tract infections
- Author
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Magdalena E. Sobieszczyk, Christine J. Kubin, Scott M. Hammer, Preeti Pancholi, Phyllis Della-Latta, Christine M. Hay, and E. Yoko Furuya
- Subjects
Microbiology (medical) ,Acinetobacter baumannii ,Adult ,Male ,medicine.medical_specialty ,Combination therapy ,medicine.drug_class ,Polymyxin ,Critical Illness ,Antibiotics ,Internal medicine ,Drug Resistance, Multiple, Bacterial ,Germany ,Administration, Inhalation ,medicine ,Humans ,Pharmacology (medical) ,Alcaligenes ,Respiratory Tract Infections ,Antibacterial agent ,Aged ,Polymyxin B ,Retrospective Studies ,Pharmacology ,Aged, 80 and over ,Respiratory tract infections ,business.industry ,Middle Aged ,Antimicrobial ,Surgery ,Anti-Bacterial Agents ,Multiple drug resistance ,Infectious Diseases ,Treatment Outcome ,Injections, Intravenous ,Pseudomonas aeruginosa ,Drug Therapy, Combination ,Female ,Kidney Diseases ,business ,Gram-Negative Bacterial Infections ,medicine.drug - Abstract
Background: The treatment of infections caused by multidrug-resistant (MDR) Gram-negative organisms poses a therapeutic challenge. The use of polymyxin B has been resurrected specifically for this purpose. Patients and methods: We retrospectively reviewed the clinical and microbiological efficacy, and safety profile of polymyxin B in the treatment of MDR Gram-negative bacterial infections of the respiratory tract. Twenty-five critically ill patients received a total of 29 courses of polymyxin B administered in combination with another antimicrobial agent. Results: Patients were treated with intravenous, and/or aerosolized polymyxin B. Mean duration of polymyxin B therapy was 19 days (range 2-57 days). End of treatment mortality was 21%, and overall mortality at discharge was 48%. Nephrotoxicity was observed in three patients (10%) and did not result in discontinuation of therapy. Conclusions: Polymyxin B in combination with other antimicrobials can be considered a reasonable and safe treatment option for MDR Gram-negative respiratory tract infections in the setting of limited therapeutic options.
- Published
- 2004
22. Contributors
- Author
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Nabih I. Abdou, Kathryn M. Abel, Judith A. Aberg, Diann M. Ackard, Jonathan D. Adachi, Jill Aimee Addesa, Robert J. Agate, Jerilyn Allen, Shilpa H. Amin, Aristotelis G. Anastasiadis, David E. Anderson, Gaya Aranoff, Arthur P. Arnold, Craig S. Atwood, Casilda Balmaceda, Promila Banerjee, Jamie S. Barkin, Shari S. Bassuk, David Bateman, Carolyn Becker, Jennifer Bell, Robert R. Bies, Kristin L. Bigos, Kathryn L. Bilello, John P. Bilezikian, Candice Bjornson, Jerry G. Blaivas, Roger S. Blumenthal, Roger Bouillon, Richard Bowen, Kimberly T. Brill, Ronald T. Burkman, William Byne, Leigh Ann Callahan, Marcia Irene Canto, Laura L. Carruth, Donald O. Castell, Lin Chang, Min C. Chen, Margaret A. Chesney, Mary Ann Chiasson, Pierre Chue, Pak Chung, Wendy K. Chung, Darryl S. Chutka, Costanza Cocilovo, Marcia L. Collaer, Hari S. Conjeevaram, Robert W. Coombs, Ann M. Coulston, Ann Cranney, Marcia Cruz-Correa, Carolyn D'Ambrosio, Kristin L. Dardano, Sai Krupa Das, L. Eugene Daugherty, Anne R. Davis, Lillian G. Dawes, Wendy Demark-Wahnefried, Dawn L. DeMeo, Dickson D. Despommier, Pamela S. Douglas, Dmitry Droggin, Catherine E. DuBeau, Alison M. Duncan, Dayna Early, Wafaa El-Sadr, Jose Erbella, William S. Evans, Kevin C. Fleming, Adam J. Flisser, David Fogelman, Gordon Ford, Susan C. Fox, Amy Foxx-Orenstein, Marilynn C. Frederiksen, James H. Garvin, John P. Gearhart, Claudia L. Ginsberg, Marc Goldstein, Raquel E. Gur, Ruben C. Gur, Christine A. Haller, Scott M. Hammer, Lynn C. Hartmann, Christine M. Hay, Megan Rist Haymart, Margaret M. Heitkemper, Dawn Hershman, Daniel L. Hogan, Carin V. Hopps, Shiew-Mei Huang, Stacy D. Jacobson, James Joseph, Gary M. Kammer, Robyn G. Karlstadt, Umaprasanna S. Karnam, Sonya Kashyap, David M. Kaufman, Steven R. Kayser, Sundeep Khosla, Nigar Kirmani, David Knopman, Tatjana Kolevska, Laurence N. Kolonel, Carol L. Kuhle, Mindy S. Kurzer, Robert G. Lahita, George M. Lazarus, Susan J. Lee, Marianne J. Legato, Jaswinder K. Legha, Lawrence J. Lesko, Jon D. Levine, Li-Ming Loh, Anne C. Looker, Franklin D. Lowy, Susmita Mallik, JoAnn E. Manson, Dawn A. Marcus, Antonio Martin, Richard A. Matthay, R. Scott McClelland, Mary Gail Mercurio, Jordan D. Metzl, Christine Miaskowski, Margaret Miller, Paul D. Miller, Jeffrey W. Milsom, Ian Mitchell, Karen L. Moncher, Lisa Moores, Martha J. Morrell, Susan Murin, Caitlin M. Nass, Alfred I. Neugut, Gwen L. Nichols, Colm J. O'Loughlin, Albert M. Ong, Jose M. Ordovas, Katherine M.A. O'Reilly, Kyriakos Papadopoulos, Alexandra Papaioannou, Ann L. Parke, George Perry, Thai Pham, William R. Phipps, Anthony P. Pietropaoli, Bruce G. Pollock, William G. Powderly, Vijaya S. Pratha, Deborah Denise Proctor, Sandhya Pruthi, Timothy J. Ramsden, Sarathchandra I. Reddy, Virginia Rider, Ellen Ritchie, Barbara H. Roberts, Susan B. Roberts, Cheryl L. Rock, Lauri Romanzi, Giuseppe M.C. Rosano, Melissa Rose, Michael R. Rosen, Tove S. Rosen, Zachary Rosner, Jennifer Rossi, Mishaela R. Rubin, Mack T. Ruffin, Donna Russo, Chandra Sahajwalla, Laurent Salomon, Hilary Sanfey, Philip M. Sarrel, Peter N. Schlegel, Janice B. Schwartz, Mary V. Seeman, Annabell C. Segarra, Christina Sekaer, Meredith Selleck, Ridwan Shabsigh, Beverley J. Sheares, Donna Shoupe, Lee P. Shulman, Edwin K. Silverman, Patricia J. Sime, Mark A. Smith, Magdalena E. Sobieszczyk, Toyooki Sonoda, Edward J. Stanford, Donald G. Stein, Richard C. Sullivan, Gerald Supinski, Maged Tanios, Mark A. Tarnopolsky, Robert Temple, Amy Tiersten, Theresa Toigo, Heather O. Tory, David R. Trawick, Simon J. Tsiouris, Marisa Tungsiripat-Gerber, Viola Vaccarino, Mark C. Valkenburgh, Dirk Vanderschueren, Johannes D. Veldhuis, Katrien Venken, Sara E. Walker, Myron L. Weisfeldt, Jeffrey P. Weiss, Timothy Wilkin, Jacqueline L. Wolf, C.R.J. Woodhouse, Michael Yin, Cosmina Zeana, and Naseem Zojwalla
- Published
- 2004
23. Gender-Specific Issues in Non-HIV Viral Infections
- Author
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Christine M. Hay and Magdalena E. Sobieszczyk
- Subjects
Pregnancy ,biology ,biology.organism_classification ,medicine.disease ,Asymptomatic ,Measles ,Virus ,Measles virus ,Pneumonia ,Immune system ,Immunology ,medicine ,Seroprevalence ,medicine.symptom - Abstract
This chapter examines gender-specific manifestations of viral infections resulting from differences in pathophysiology, viral infections resulting from differences in exposures or risk factors, and manifestations specific to pregnancy. Human T-cell lymphotropic virus type 1 (HTLV-1) seroprevalence is characterized by an age-dependent increase that is similar in diverse geographic areas. Starting with adolescence, however, the prevalence increases and infection rates between males and females diverge, with female rates exceeding male rates. This trend continues into adulthood, and whereas male rates plateau by the age of 40 years, female rates continue to increase and peak at about the age of 60 years. Asymptomatic viruria with Human polyomaviruses JC and B K virus occurs primarily in immunosuppressed patients and pregnant women; in humans with intact immune function it is a rare occurrence.The morbidity and mortality of measles are higher in pregnant women mostly because of an increased risk of measles virus pneumonia during the third trimester and puerperium.
- Published
- 2004
24. Immune Control of HIV-1 Replication
- Author
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Eric S. Rosenberg, Nesli Basgoz, Otto O. Yang, Bruce D. Walker, and Christine M. Hay
- Subjects
biology ,business.industry ,Human immunodeficiency virus (HIV) ,Immune control ,biology.organism_classification ,medicine.disease_cause ,Antiretroviral therapy ,Virology ,Virus ,Immune system ,Retrovirus ,Immunity ,Medicine ,business ,Viral load - Abstract
Over 30 million persons are infected with HIV-1 worldwide, and over 8000 new infections occur every day1. Although there have been enormous advances in antiretroviral therapy against this retrovirus, economic constraints mean that over 90% of infected persons will never benefit from these therapies. The only solution for the global epidemic is the development of an effective vaccine. Such development is predicated on the assumption that this virus can be contained by immune responses. Recent evidence now supports the contention that effective immunity can be generated in natural infection, and this provides encouragement for accelerated vaccine efforts.
- Published
- 1998
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