17 results on '"Treanor, John J."'
Search Results
2. Stable emulsion (SE) alone is an effective adjuvant for a recombinant, baculovirus-expressed H5 influenza vaccine in healthy adults: A Phase 2 trial.
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Treanor, John J., Chu, Laurence, Essink, Brandon, Muse, Derek, El Sahly, Hana M., Izikson, Ruvim, Goldenthal, Karen L., Patriarca, Peter, and Dunkle, Lisa M.
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EMULSIONS , *INFLUENZA vaccines , *RECOMBINANT baculoviruses , *IMMUNOLOGICAL adjuvants , *SEROCONVERSION - Abstract
Background Influenza A viruses of the H5 subtype have been identified as important targets for development of vaccines. Achievement of potentially protective antibody responses against pandemic strains has usually required the use of adjuvants. Objectives We evaluated a candidate A/Indonesia/05/2005 (H5) vaccine generated by baculovirus expression of recombinant hemagglutinin (HA) protein with or without stable emulsion (SE) as an adjuvant. Methods Healthy subjects 18–49 years old were randomized (1:1:1:1) to receive two doses of rHA at 7.5 ug per dose (no adjuvant), or 3.8 ug, 7.5 ug, or 15 ug per dose formulated with 2% SE separated by 21 days, and serum from day 0, 21, 42, and 201 assessed by hemagglutination-inhibition. Results 341 subjects were enrolled in the study and 321 received two doses of vaccine. Vaccination was well tolerated in all groups. After two doses, seroconversion was noted in only 9% (95% confidence interval 4%, 17%) of recipients of unadjuvanted vaccine at 7.5 ug, but in 70% (59%, 80%), 76% (65%, 85%), and 83% (73%, 91%) of those receiving adjuvanted vaccine at 3.8 ug, 7.5 ug, or 15 ug respectively. Conclusions Stable emulsion alone is an effective adjuvant for rH5 vaccine in healthy adults. All three adjuvanted dose groups met the current criterion for seroconversion rate for pandemic vaccines. This dose-ranging study also identified a group (15 ug per dose formulated with 2% SE) that met the criteria for both seroconversion and percentage of subjects achieving an HI antibody titer ⩾ 40. These Phase 2 data support the further clinical development of SE adjuvanted Panblok H5. Clinical trial registration: NCT01612000 . The protocol was approved by the relevant Institutional Review Board for each study site, and the study was conducted in accordance with the Declaration of Helsinki, International Conference of Harmonisation – Good Clinical Practice, and all applicable laws and regulations. All participants provided written informed consent before study procedures. [ABSTRACT FROM AUTHOR]
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- 2017
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3. High-Affinity H7 Head and Stalk Domain-Specific Antibody Responses to an Inactivated Influenza H7N7 Vaccine After Priming With Live Attenuated Influenza Vaccine.
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Halliley, Jessica L., Khurana, Surender, Krammer, Florian, Fitzgerald, Theresa, Coyle, Elizabeth M., Ka Yan Chung, Baker, Steven F., Hongmei Yang, Martínez-Sobrido, Luis, Treanor, John J., Subbarao, Kanta, Hana Golding, Topham, David J., Sangster, Mark Y., Chung, Ka Yan, Yang, Hongmei, and Golding, Hana
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INFLUENZA vaccines ,AVIAN influenza A virus ,HEMAGGLUTININ ,IMMUNOGLOBULINS ,B cells ,EPITOPES ,IMMUNOLOGIC memory ,T-test (Statistics) ,INFLUENZA prevention ,HEMAGGLUTINATION tests ,INFLUENZA ,LONGITUDINAL method ,RESEARCH funding ,VACCINES ,VIRAL antibodies ,INFLUENZA A virus ,NEUTRALIZATION tests - Abstract
Recent studies have shown that live attenuated influenza vaccines (LAIVs) expressing avian influenza virus hemagglutinins (HAs) prime for strong protective antibody responses to an inactivated influenza vaccine (IIV) containing the HA. To better understand this priming effect, we compared H7 HA head and stalk domain-specific B-cell responses in H7N7 LAIV-primed subjects and non-H7-primed controls after a single dose of H7N7 IIV. As previously reported, H7N7 LAIV-primed subjects but not control subjects generated strong hemagglutination-inhibiting and neutralizing antibody responses to the H7N7 IIV. Here, we found that the quantity, epitope diversity, and affinity of H7 head-specific antibodies increased rapidly in only H7N7 LAIV-primed subjects after receipt of the IIV. However, all cohorts generated a vigorous, high-affinity, stalk-specific antibody response. Consistent increases in circulating memory B-cell frequencies after receipt of the IIV reflected the specificity of high-affinity antibody production. Our findings emphasize the value of LAIVs as a vehicle for prepandemic vaccination. [ABSTRACT FROM AUTHOR]
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- 2015
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4. 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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5. Characterisation of a wild-type influenza (A/H1N1) virus strain as an experimental challenge agent in humans.
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Watson, Jeannette M., Francis, James N., Mesens, Sofie, Faiman, Gabriel A., Makin, Jill, Patriarca, Peter, Treanor, John J., Georges, Bertrand, and Bunce, Campbell J.
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INFLUENZA A virus, H1N1 subtype ,VIRAL shedding ,IMMUNOREGULATION ,ANTIVIRAL agents ,VIRAL vaccines ,CLINICAL drug trials ,VACCINES - Abstract
Background: Human challenge models using respiratory viruses such as influenza are increasingly utilised in the development of novel vaccines and anti-viral modalities and can provide preliminary evidence of protection before evaluation in field trials. We describe the results of a clinical study characterising an A/H1N1 influenza challenge virus in humans. Methods: The challenge agent, influenza A/California/2009 (H1N1), was manufactured under cGMP conditions and characterised in accordance with regulatory guidelines. A dose-ascending open-label clinical study was conducted in 29 healthy young adults screened sero-negative to the challenge strain. Subjects were intranasally inoculated with three increasing doses of virus and physician-reported signs, subjected-reported symptoms, viral shedding and immunological responses were monitored. Results: A dose-dependent increase in clinical signs and symptoms was observed with 75% of subjects developing laboratory-confirmed illness at the highest inoculum (3.5 × 10
6 TCID50 ). At the highest dose, physician or subjectreported signs of infection were classified as mild (all subjects), moderate (50%) and severe (16%) with peak symptoms recorded four days after infection. Clinical signs were correlated with nasal mucus weight (P < .001) and subject-reported symptoms (P < .001). Geometric mean peak viral shedding was log10 5.16 TCID50 and occurred three days after inoculation with a median duration of five days. The safety profile was such that physiological responses to viral infection were mainly restricted to the upper airways but were not of such severity to be of clinical concern. Conclusions: A highly characterised wild-type Influenza A/California/2009 (H1N1) virus manufactured for clinical use was shown to induce a good infectivity profile in human volunteers. This clinical challenge model can be used for evaluating potential efficacy of vaccines and anti-viral therapeutics. [ABSTRACT FROM AUTHOR]- Published
- 2015
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6. 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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7. Transient decrease in human peripheral blood myeloid dendritic cells following influenza vaccination correlates with induction of serum antibody.
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Kobie, James J., Treanor, John J., and Ritchlin, Christopher T.
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DENDRITIC cells , *INFLUENZA vaccines , *SERUM , *IMMUNE response , *MONOCYTES , *HOMEOSTASIS , *BIOMARKERS , *PHYSIOLOGY - Abstract
Dendritic cells (DC) are critical inducers of the adaptive immune response. Extensive characterization of tissue-resident and monocyte-derived DC has revealed diverse stimulatory and regulatory actions, although the role of peripheral blood dendritic cells (PBDC) in maintaining homeostasis remains unclear. Examination of various myeloid (CD11c+CD303-) and plasmacytoid (CD11c-CD303+) DC populations in the peripheral blood of seasonal trivalent inactivated influenza vaccine recipients revealed a transient decrease in the frequency of CD11c+CD1c- myeloid DC subsets 5-10 days following vaccination, including both CD141+ and CD141- myeloid DC subsets of this population. These populations rebounded by 1 month, while plasmacytoid DC remained stable. The magnitude of the decrease in the CD141+ myeloid DC subset at d5-7 significantly correlated with the induction of influenza specific serum antibodies measured at 1 month following vaccination. These results demonstrate a mobilization of peripheral blood myeloid DC following vaccination and indicate these cells are potential biomarkers of immune response. [ABSTRACT FROM AUTHOR]
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- 2014
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8. Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine.
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He, Xiao-Song, Sasaki, Sanae, Baer, Jane, Khurana, Surender, Golding, Hana, Treanor, John J., Topham, David J., Sangster, Mark Y., Jin, Hong, Dekker, Cornelia L., Subbarao, Kanta, and Greenberg, Harry B.
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B cells ,H5N1 Influenza ,INFLUENZA vaccines ,YOUNG adults ,OLDER people ,BIOLOGICAL assay ,TARGETED drug delivery - Abstract
Background. The generation of heterovariant immunity is a highly desirable feature of influenza vaccines. The goal of this study was to compare the heterovariant B-cell response induced by the monovalent inactivated 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) vaccine with that induced by the 2009 seasonal trivalent influenza vaccine (sTIV) containing a seasonal influenza A virus subtype H1N1 (A[H1N1]) component in young and elderly adults.Methods. Plasmablast-derived polyclonal antibodies (PPAb) from young and elderly recipients of A(H1N1)pdm09 vaccine or sTIV were tested for binding activity to various influenza antigens.Results. In A(H1N1)pdm09 recipients, the PPAb titers against homotypic A(H1N1)pdm09 vaccine were similar to those against the heterovariant seasonal A(H1N1) vaccine and were similar between young and elderly subjects. The PPAb avidity was higher among elderly individuals, compared with young individuals. In contrast, the young sTIV recipients had 10-fold lower heterovariant PPAb titers against the A(H1N1)pdm09 vaccine than against the homotypic seasonal A(H1N1) vaccine. In binding assays with recombinant head and stalk domains of hemagglutinin, PPAb from the A(H1N1)pdm09 recipients but not PPAb from the sTIV recipients bound to the conserved stalk domain.Conclusion. The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain. [ABSTRACT FROM AUTHOR]
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- 2013
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9. Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response
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Taylor, David N., Treanor, John J., Sheldon, Eric A., Johnson, Casey, Umlauf, Scott, Song, Langzhou, Kavita, Uma, Liu, Ge, Tussey, Lynda, Ozer, Karen, Hofstaetter, Thomas, and Shaw, Alan
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HEMAGGLUTININ , *IMMUNE response , *FLAGELLIN , *INFLUENZA vaccines , *VACCINE safety , *SEROCONVERSION , *MEDICAL statistics , *CLINICAL trials - Abstract
Abstract: Background: We evaluated the safety and immunogenicity profiles of 3 novel influenza vaccine constructs consisting of the globular head of the HA1 domain of the Novel H1N1 genetically fused to the TLR5 ligand, flagellin. HA1 was fused to the C-terminus of flagellin in VAX128A, replaced the D3 domain of flagellin in VAX128B and was fused in both positions in VAX128C. Methods: In a dose escalation trial, 112 healthy subjects 18–49 and 100 adults ≥65 years old were enrolled in a double blind, placebo controlled clinical trial at two centers. Vaccines were administered IM at doses ranging from 0.5 to 20μg. VAX128C was selected for second study performed in 100 subjects 18–64 years old comparing 1.25 and 2.5μg doses. All subjects were followed for safety and sera collected pre- and post-vaccination were tested by hemagglutination-inhibition (HAI). Serum C-reactive protein and cytokine levels were also measured. Conclusions: In the first study high HAI titers and high seroconversion and seroprotection rates were observed at doses ≥2.5μg in adults 18–49. In adults ≥65 years, the vaccines doses of ≥4μg were required to induce a ≥4-fold rise in HAI titer, 50% seroconversion and 70% seroprotection. Based on safety, VAX128A was tested up to 8μg, VAX128B to 16μg and VAX128C to 20μg. Dose escalation for VAX128A was stopped at 8μg because one subject had temperature 101.6°F associated with a high CRP response, VAX128B was stopped at 16μg because of a severe AE associated with a high CRP and IL-6 response. VAX128C was not stopped before reaching the 20μg dose. In the second study VAX128C was well tolerated among 100 subjects who received 1.25 or 2.5μg. The peak GMT was 385 (95%CI 272–546), 79% (71–87%) seroconversion and 92% (84–96%) seroprotection. Discussion: Flagellin adjuvanted vaccines can be designed to minimize reactogenicity and retain immunogenicity, thereby representing a promising next generation vaccine technology. [Copyright &y& Elsevier]
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- 2012
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10. Induction of a potent immune response in the elderly using the TLR-5 agonist, flagellin, with a recombinant hemagglutinin influenza–flagellin fusion vaccine (VAX125, STF2.HA1 SI)
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Taylor, David N., Treanor, John J., Strout, Cynthia, Johnson, Casey, Fitzgerald, Theresa, Kavita, Uma, Ozer, Karen, Tussey, Lynda, and Shaw, Alan
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IMMUNE response , *INFLUENZA vaccines , *HEMAGGLUTININ , *RECOMBINANT proteins , *SEROLOGY , *INFLUENZA viruses , *ESCHERICHIA coli , *NATURAL immunity - Abstract
Abstract: Background: Influenza vaccines perform poorly in the elderly with reduced serological response and vaccine efficacy. 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 Escherichia coli. Methods: 120 subjects ≥65 years old were enrolled at three clinical centers. VAX125 vaccine was administered at doses of 0.5, 1, 2, 3, 5 or 8μg delivered i.m. as a single dose vaccination on Day 0 using a dose-escalation with 20 subjects in each dose level. Subjects were followed for adverse events and sera were tested by hemagglutination-inhibition (HAI) against egg-grown virus on days 0, 7, 14, and 28. Serum C-reactive protein (CRP) and anti-flagellin antibody were also assessed. Results: The mean age was 71 years. The vaccine was well tolerated at all dose levels, with no more than mild to moderate local or systemic symptoms. The geometric mean titers (GMT) increased in all dose groups. In the 5μg group the day 14 post-vaccination HAI titer was 1:226 showing a 12-fold increase over baseline. The 8μg group showed a similar post-vaccination GMT increase (∼8-fold). In the combined 5 and 8μg groups, the seroconversion rate was 75% and the seroprotection rate was 98%. Conclusions: A 5μg dose of VAX125 was safe and able to induce a greater than 10-fold increase HAI antibody levels and nearly complete seroprotection in subjects over 65 years old. The use of flagellin to adjuvant influenza vaccines via the TLR5 innate immune pathway appears to be a useful approach to overcome poor immune responses in the elderly. VAX125 is a promising new candidate for prevention of influenza A disease in both young adults and the elderly. [Copyright &y& Elsevier]
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- 2011
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11. Safety and immunogenicity of a recombinant hemagglutinin influenza–flagellin fusion vaccine (VAX125) in healthy young adults
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Treanor, John J., Taylor, David N., Tussey, Lynda, Hay, Christine, Nolan, Carrie, Fitzgerald, Theresa, Liu, Ge, Kavita, Uma, Song, Langzhou, Dark, Irving, and Shaw, Alan
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HEMAGGLUTININ , *INFLUENZA vaccines , *LIGANDS (Biochemistry) , *C-reactive protein , *IMMUNOGLOBULINS , *CLINICAL trials , *GEOMETRIC analysis - Abstract
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 0.1μg, 0.3μg, 1μg, 2μg, 3μg, 5μg and 8μg to groups of 8 subjects each. Stage 2 was a double-blind, placebo-controlled study in which subjects were randomized to receive 1.0μg and 2.0μg VAX125 vaccine doses or placebo, with 16 subjects per group. Finally, an additional 24 subjects received a 0.5μg 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 8μg, 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 0.5μg or greater, including in 46 of 72 subjects who received doses from 0.5μg to 2μg. 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. [Copyright &y& Elsevier]
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- 2010
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12. Editorial Commentary: Influenza Vaccine: Glass Half Full or Half Empty?
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Treanor, John J. and Szilagyi, Peter
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INFLUENZA vaccines , *INFLUENZA , *COHORT analysis , *POLYMERASE chain reaction , *MEDICAL care - Abstract
The author discusses the assessment of influenza vaccine effectiveness during the 2010–2011 influenza season, using a nonrandomized, prospectively followed cohort analysis. It reports two findings which includes the rate of polymerase chain reaction–documented influenza illness was not substantially different and influenza vaccination in a previous season may have impacted the effectiveness of the vaccine in the current season.
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- 2013
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13. Comparison of Serum Hemagglutinin and Neuraminidase Inhibition Antibodies After 2010–2011 Trivalent Inactivated Influenza Vaccination in Healthcare Personnel.
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Laguio-Vila, Maryrose R., Thompson, Mark G., Reynolds, Sue, Spencer, Sarah M., Gaglani, Manjusha, Naleway, Allison, Ball, Sarah, Bozeman, Sam, Baker, Steven, Martínez-Sobrido, Luis, Levine, Min, Katz, Jackie, Fry, Alicia M., and Treanor, John J.
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HEMAGGLUTININ ,BLOOD agglutination ,AGGLUTININS ,NEURAMINIDASE ,GLYCOSIDASES - Abstract
Background. Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA.Methods. Serum of 1349 healthcare personnel (HCP) electing or declining the 2010–2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection.Results. In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009–2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections.Conclusions. Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity. [ABSTRACT FROM PUBLISHER]
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- 2015
14. Vaccination with drifted variants of avian H5 hemagglutinin protein elicits a broadened antibody response that is protective against challenge with homologous or drifted live H5 influenza virus
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Santiago, Felix W., Fitzgerald, Theresa, Treanor, John J., and Topham, David J.
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VACCINATION , *HEMAGGLUTININ , *IMMUNOGLOBULINS , *INFLUENZA viruses , *HOMOLOGY (Biology) , *IMMUNE response , *ENZYME-linked immunosorbent assay , *ANIMAL models in research - Abstract
Abstract: Substantial H5 influenza HA directed immunity is elicited after vaccination of human subjects who had been previously immunized with a drifted H5 HA variant. We sought to investigate the characteristics of H5 HA specific immune responses in more depth by developing an animal model of H5 HA vaccination using drift variants of recombinant H5 HA proteins. HA proteins derived from influenzas A/Vietnam/1203/04 (Clade 1) and A/Indonesia/05/05 (Clade 2.1) were chosen. The sequence of vaccination consisted of two doses of homologous protein, followed by one additional dose of the homologous or heterologous, drifted HA protein. Each dose of HA was combined with CpG as an adjuvant and was injected subcutaneously. All the animals exhibited a serum IgG antibody response that cross-reacted with both HAs in an ELISA. However, those animals that received the drifted variant exhibited higher reactivity to the heterologous HA. Competitive ELISA of serum from drift-variant recipients showed evidence of antibody focusing towards the drifted HA, suggesting modification of the response towards improved cross-reactivity, though development of neutralizing antibodies was limited. Nevertheless, animals were protected against live-virus challenge, and passive transfer of serum was sufficient to confer protection to otherwise naïve mice, indicating that both neutralizing and non-neutralizing antibodies offer some degree of protection. These findings suggest that pre-vaccination against H5 influenza has the potential to prime immunity against emerging drifted H5 strains, and could also lower the dose requirements of vaccination in the event of a pandemic. [Copyright &y& Elsevier]
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- 2011
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15. 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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16. Antigenic and immunogenic properties of recombinant hemagglutinin proteins from H1N1 A/Brisbane/59/07 and B/Florida/04/06 when produced in various protein expression systems
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Santiago, Felix W., Lambert Emo, Kris, Fitzgerald, Theresa, Treanor, John J., and Topham, David J.
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HEMAGGLUTININ , *H1N1 influenza , *IMMUNOGLOBULINS , *INFLUENZA vaccines , *CELL culture , *IMMUNE response , *VACCINATION , *VIRAL proteins - Abstract
Abstract: Antibodies directed against the influenza hemagglutinin (HA) protein largely mediate virus neutralization and confer protection against infection. Consequently, many studies and assays of influenza vaccines are focused on HA-specific immune responses. Recombinant HA (rHA) proteins can be produced in a number of protein expression and cell culture systems. These range from baculovirus infection of insect cell cultures, to transient transfection of plants, to stably transfected human cell lines. Furthermore, the rHA proteins may contain genetic modifications, such as histidine tags or trimerization domains, intended to ease purification or enhance protein stability. However, no systematic study of these different forms of the HA protein have been conducted. It is not clear which, if any, of these different protein expression systems or structural modifications improve or diminish the biological behavior of the proteins as immunogens or antigens in immune assays. Therefore we set out to perform systematic evaluation of rHA produced in different proteins expression systems and with varied modifications. Five rHA proteins based on recent strains of seasonal influenza A and five based on influenza B HA were kindly provided by the Biodefense and Emerging Infections Reagent Repository (BEIR). These proteins were evaluated in a combination of biochemical and structural assays, in vitro humoral and cellular immune assays, and in an animal vaccination model. Marked differences in the behavior of the individual proteins was evident suggesting that they are not equal when being used to detect an immune response. They were, nevertheless, similar at eliciting neutralizing antibody responses. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
17. Identification of HLA class II H5N1 hemagglutinin epitopes following subvirion influenza A (H5N1) vaccination
- Author
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Zinckgraf, John W., Sposato, Margaret, Zielinski, Veronica, Powell, Doug, Treanor, John J., and von Hofe, Eric
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EPITOPES , *HLA class II antigens , *HEMAGGLUTININ , *INFLUENZA vaccines , *VIRION , *INFLUENZA A virus , *CELLULAR immunity , *IMMUNOGENETICS , *T cells - Abstract
Abstract: Prophylactic immunization against influenza infection requires CD4+ T-helper cell activity for optimal humoral and cellular immunity. Currently there is one FDA approved H5N1 subvirion vaccine available, although stockpiles of this vaccine are insufficient for broad population coverage and the vaccine has only demonstrated modest immunogenicity. Specific activation of CD4+ T-helper cells using class II H5N1 HA peptide vaccines may be a useful component in immunization strategy and design. Identification of HLA class II HA epitopes was undertaken in this report by obtaining PBMCs from volunteers previously immunized with an H5N1 inactivated subvirion vaccine, followed by direct ex vivo stimulation of CD4+ T cells against different sources of potential HA class II epitopes. In the 1st round of analysis, 35 donors were tested via IFN-γ ELISPOT using pools of overlapping HA peptides derived from the H5N1 A/Thailand/4(SP-528)/2004 virus, recombinant H5N1 (rHA) and inactivated H5N1 subvirion vaccine. In addition, a series of algorithm-predicted epitopes coupled with the Ii-Key moiety of the MHC class II-associated invariant chain for enhanced MHC class II charging were also included. Specific responses were observed for all 20 peptide pools, with 6–26% of vaccinated individuals responding to any given pool (donor response frequency) and a magnitude of response ranging from 3- to >10-fold above background levels. Responses were similarly observed with the majority of algorithm-predicted epitopes, with a donor response frequency of up to 29% and a magnitude of response ranging from 3–10-fold (11/24 peptides) to >10-fold above background (7/24 peptides). PBMCs from vaccine recipients that had detectable responses to H5N1 rHA following 1st round analysis were used in a 2nd round of testing to confirm the identity of specific peptides based on the results of the 1st screening. Sixteen individual HA peptides identified from the library elicited CD4+ T cell responses between 3- and >10-fold above background, with two peptides being recognized in 21% of recipients tested. Eight of the putative MHC class II epitopes recognized were found in regions showing partial to significant sequence homology with New Caledonia H1N1 influenza HA, while eight were unique to H5N1 HA. This is the first study to identify H5N1 HA epitope-specific T cells in vaccine recipients and offers hope for the design of a synthetic peptide vaccine to prime CD4+ T-helper cells. Such a vaccine could be used to provide at least some minimal level of H5N1 protection on its own and/or prime for a subsequent dose of a more traditional but supply-limited vaccine. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
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