J D Boyer

The Children's Hospital of Philadelphia, Philadelphia, PA, United States

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Publications (81)402.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1-infected individuals, despite antiretroviral-therapy, often have impaired vaccine responses. We examined the role that immune activation and cellular phenotypes play in H1N1-vaccine responsiveness in HIV-infected-subjects on ART. Subjects received the H1N1-vaccine (15 µg-dose;Novartis), baseline and post-immunization antibody titers were evaluated, and classified as responders if at W3 sero-protection guidelines were met. Responders had higher percentages of baseline naïve T-cells and lower percentages of terminally-differentiated T-cells versus non-responders. Additionally, the naïve CD4+ T-cell percentage and age were negatively correlated. Preservation of naïve T-cell populations, by starting therapy early could impact vaccine responses against influenza and other pathogens, especially as this population ages.
    The Journal of Infectious Diseases 03/2014; · 5.85 Impact Factor
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    ABSTRACT: To examine the effect of chemotherapy for ovarian cancer on immunologic function and to define the effect on the serologic response to the influenza vaccine. Under IRB approved protocols, patients with ovarian cancer were administered seasonal trivalent killed influenza vaccines. Peripheral blood was collected for immunologic assessments. Serum was analyzed for hemagglutination inhibition (HAI) antibody titers. Peripheral blood mononuclear cells were isolated to characterize T and B cell populations and function. Thirty-one patients were recruited: 13 in remission receiving a dendritic cell vaccine with or without a single dose of low-dose cyclophosphamide, 3 in remission not receiving treatment, and 15 undergoing standard therapy. Significant effects on T cell and B cell subset distributions were seen. Functional effects were also seen. Few patients were able to mount a 4-fold HAI antibody response. A 4-fold response was observed for H1N1 in 20%, for H3N2 in 26%, and for influenza B in 6%. Pre-existing exposure to influenza was predictive of responders. Despite CDC recommendations that patients undergoing chemotherapy receive influenza vaccine, there is little evidence to support its serologic effectiveness in this population. Patients with ovarian cancer are almost uniformly unable to mount a meaningful antibody response. These findings have serious implications for future resource allocation for both seasonal and novel pandemic influenza outbreak and understanding the immunologic deficits as a result of chemotherapy may improve patient care.
    Vaccine 09/2013; · 3.77 Impact Factor
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    ABSTRACT: Background. DNA vaccines have been very poorly immunogenic in humans but have been an effective priming modality in prime-boost regimens. Methods to increase the immunogenicity of DNA vaccines are needed.Methods. HIV Vaccine Trials Network (HVTN) studies 070 and 080 were multicenter, randomized, clinical trials. The human immunodeficiency virus type 1 (HIV-1) PENNVAX®-B DNA vaccine (PV) is a mixture of 3 expression plasmids encoding HIV-1 Clade B Env, Gag, and Pol. The interleukin 12 (IL-12) DNA plasmid expresses human IL-12 proteins p35 and p40. Study subjects were healthy HIV-1-uninfected adults 18-50 years old. Four intramuscular vaccinations were given in HVTN 070, and 3 intramuscular vaccinations were followed by electroporation in HVTN 080. Cellular immune responses were measured by intracellular cytokine staining after stimulation with HIV-1 peptide pools.Results. Vaccination was safe and well tolerated. Administration of PV plus IL-12 with electroporation had a significant dose-sparing effect and provided immunogenicity superior to that observed in the trial without electroporation, despite fewer vaccinations. A total of 71.4% of individuals vaccinated with PV plus IL-12 plasmid with electroporation developed either a CD4(+) or CD8(+) T-cell response after the second vaccination, and 88.9% developed a CD4(+) or CD8(+) T-cell response after the third vaccination.Conclusions. Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.
    The Journal of Infectious Diseases 07/2013; · 5.85 Impact Factor
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    ABSTRACT: BACKGROUND: Donor leukocyte infusions (DLI) can induce potent graft-versus-leukemia (GvL) activity for patients with relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, except for chronic phase chronic myelogenous leukemia, responses to DLI have been disappointing. GvL induction is likely to be most effective in the setting of minimal residual disease. Therefore, prevention of relapse by using DLI prophylactically for high-risk patients may improve outcomes of allogeneic HSCT. We have previously reported that ex-vivo co-stimulated T cells infusions (activated DLI, or aDLI) as treatment for relapse are safe and have potent GvL effects. We hypothesized that prophylactic aDLI can be given safely and prevent relapse in high-risk patients after allogeneic HSCT. METHODS: Eighteen patients with AML (14), ALL (3), or MDS (1) received allogeneic SCT after a reduced intensity-conditioning (RIC) regimen with alemtuzumab, fludarabine, and busulfan. Graft-versus-host-disease (GvHD) prophylaxis consisted of tacrolimus and methotrexate with a planned early and rapid taper of tacrolimus. Patients without GvHD, off immune suppression and in remission received aDLI at a dose of 1 x10(7) CD3+ cells/kg (aDLI #1) at D+120, and a second infusion of 1 x 10(8) CD3 cells/kg (aDLI #2) at D+180. RESULTS: At median follow-up of 58 months, 5/18 (28%) patients are alive and 4 remain in remission. Eleven (65%) relapsed at median time of 191 days. Twelve of 18 patients received at least one aDLI. Six of the 12 aDLI#1 patients also received aDLI#2. Six patients did not receive any aDLI due to early relapse (2), protocol ineligibility (1), and GvHD (3). Of the 12 patients who received aDLI#1, only 2/12 developed GVHD. Two out of 12 patients remain in remission. Disease recurrence was the cause of death in 10/13 (77%) patients who died. CONCLUSION: Prophylactic ex-vivo co-stimulated CD3/CD28 DLI is safe, feasible, and not associated with significant GvHD. Relapse remains the major cause of treatment failure after RIC HSCT even with rapid withdrawal of immune suppression and the use of prophylactic aDLI. Better strategies to prevent relapse are needed.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2013; · 3.15 Impact Factor
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    ABSTRACT: Abstract Stress is implicated in the pathogenesis and progression of HIV. The Transcendental Meditation (TM) is a behavioral stress reduction program that incorporates mind-body approach, and has demonstrated effectiveness in improving outcomes via stress reduction. We evaluated the feasibility of implementing TM and its effects on outcomes in persons with HIV. In this community-based single blinded Phase-I, randomized controlled trial, outcomes (psychological and physiological stress, immune activation, generic and HIV-specific health-related quality of life, depression and quality of well-being) were assessed at baseline and at six months, and were compared using parametric and nonparametric tests. Twenty-two persons with HIV were equally randomized to TM intervention or healthy eating (HE) education control group. Retention was 100% in TM group and 91% in HE control group. The TM group exhibited significant improvement in vitality. Significant between group differences were observed for generic and HIV-specific health-related quality of life. Small sample size may possibly limit the ability to observe significant differences in some outcomes. TM stress reduction intervention in community dwelling adults with HIV is viable and can enhance health-related quality of life. Further research with large sample and longer follow-up is needed to validate our results.
    AIDS Care 02/2013; · 1.60 Impact Factor
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    ABSTRACT: Chinese translation BACKGROUND: HIV-infected persons have less robust antibody responses to influenza vaccines. OBJECTIVE: To compare the immunogenicity of high-dose influenza vaccine with that of standard dosing in HIV-positive participants. DESIGN: Randomized, double-blind, controlled trial. (ClinicalTrials.gov: NCT01262846) SETTING: The MacGregor Clinic of the Hospital of the University of Pennsylvania, Philadelphia, from 27 October 2010 to 27 March 2011. PARTICIPANTS: HIV-infected persons older than 18 years. INTERVENTION: Participants were randomly assigned to receive either a standard dose (15 mcg of antigen per strain) or a high dose (60 mcg/strain) of the influenza trivalent vaccine. MEASUREMENTS: The primary end point was the rate of seroprotection, defined as antibody titers of 1:40 or greater on the hemagglutination inhibition assay 21 to 28 days after vaccination. The primary safety end point was frequency and intensity of adverse events. Secondary end points were seroconversion rate (defined as a greater than 4-fold increase in antibody titers) and the geometric mean antibody titer. RESULTS: 195 participants enrolled, and 190 completed the study (93 in the standard-dose group and 97 in the high-dose group). The seroprotection rates after vaccination were higher in the high-dose group for the H1N1 (96% vs. 87%; treatment difference, 9 percentage points [95% CI, 1 to 17 percentage points]; P = 0.029), H3N2 (96% vs. 92%; treatment difference, 3 percentage points [CI, -3 to 10 percentage points]; P = 0.32), and influenza B (91% vs. 80%; treatment difference, 11 percentage points [CI, 1 to 21 percentage points]; P = 0.030) strains. Both vaccines were well-tolerated, with myalgia (19%), malaise (14%), and local pain (10%) the most frequent adverse events. LIMITATIONS: The effectiveness of the vaccine in preventing clinical influenza was not evaluated. The number of participants with CD4 counts less than 0.200 × 109 cells/L was limited. CONCLUSION: HIV-infected persons reach higher levels of influenza seroprotection if vaccinated with the high-dose trivalent vaccine than with the standard-dose. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases and Center for AIDS Research of the University of Pennsylvania.
    Annals of internal medicine 01/2013; 158(1):19-26. · 13.98 Impact Factor
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    ABSTRACT: We report the safety and tolerability of 87 infusions of lentiviral vector modified autologous CD4 T cells (VRX496-T; Lexgenleucel-T) in 17 HIV patients with well controlled viremia. Antiviral effects were studied during analytic treatment interruption in a subset of 13 patients. VRX496-T was associated with a decrease in viral load set points in 6/8 subjects (p=0.08) In addition, A-to-G transitions were enriched in HIV sequences post infusion, consistent with a model where transduced CD4 T cells exert anti-sense mediated genetic pressure on HIV during infection. Engraftment of vector modified CD4 T cells was measured in gut associated lymphoid tissue (GALT), and correlated with engraftment in blood. The engraftment half-life in the blood was approximately 5 weeks, with stable persistence in some patients for up to five years. Conditional replication of VRX496 was detected periodically through one year post infusion. No evidence of clonal selection of lentiviral vector transduced T cells or integration enrichment near oncogenes was detected. This is the first demonstration that gene modified cells can exert genetic pressure on HIV. Thus gene modified T cells have the potential to decrease the fitness of HIV-1, and conditionally replicative lentiviral vectors have a promising safety profile in T cells. (Study registered at clinical trials.gov #NCT00295477).
    Blood 12/2012; · 9.78 Impact Factor
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    ABSTRACT: Please cite this paper as: Kersun et al. (2012) A prospective study of chemotherapy immunologic effects and predictors of humoral influenza vaccine responses in a pediatric oncology cohort. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12058. Background:  Pediatric oncology patients represent a cohort of individuals uniquely at risk of complications from influenza, yet less likely to respond to the vaccine. It is not yet clear how to best protect this vulnerable population. Methods:  We performed a prospective analysis of 177 pediatric oncology patients to define the predictors of influenza vaccine responses. Each variable was examined over three time points and a repeated measure analysis was performed. Results:  Patients with ALL vaccinated during induction phase had superior influenza vaccine responses than those subjects vaccinated during post-induction or maintenance phases (P = 0·0237). Higher aggregate HAI titer responses were associated with a higher baseline B-cell count (P = 0·0240), and higher CD4 and CD8 influenza-specific T-cell responses, suggesting prior antigen exposure is a significant contributor. The solid tumor cohort had equivalent responses during all time frames of chemotherapy. Discussion:  The optimal protection from influenza of pediatric patients on chemotherapy should include vaccination, but it is clear that not all patients produce high titers of antibodies after vaccination. This study identified biomarkers that could be used to individualize vaccine approaches. Immunologic predictors might have a role in targeting resources, as B-cell counts predicted of vaccine responses among the patients with ALL.
    Influenza and Other Respiratory Viruses 11/2012; · 1.47 Impact Factor
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    ABSTRACT: PURPOSE: Children with high-risk neuroblastoma have a poor prognosis with chemotherapy alone and hematopoietic stem cell transplantation offers improved survival. As a dose escalation strategy, tandem transplants have been utilized, but are associated with persistent immune compromise. This study evaluated the provision of an autologous co-stimulated, activated T cell product to support immunologic function. EXPERIMENTAL DESIGN: Nineteen subjects with high risk neuroblastoma were enrolled in a pilot phase and twenty three subjects were entered in to the randomized study. Immunologic reconstitution was defined by flow cytometry and functional assays. Next generation sequencing was performed to identify changes to the T cell repertoire. Twenty-two patients were vaccinated to define effects on antibody responses. RESULTS: Subjects who received their autologous co-stimulated T cell product on Day 2 had significantly superior T cell counts and T cell proliferation compared to those who received T cells on Day 90. Early administration of autologous T cells suppressed oligoclonality and enhanced repertoire diversity. The subjects who received the Day 2 T cell product also had better responses to the pneumococcal vaccine. CONCLUSIONS: The infusion of activated T cells can improve immunologic function especially when given early after transplant. This study demonstrated the benefit of providing cell therapies during periods of maximum lymphopenia.
    Clinical Cancer Research 10/2012; · 7.84 Impact Factor
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    ABSTRACT: The efficacy of influenza vaccination in patients treated with rituximab is a clinically important question. Rheumatology clinics are populated with patients receiving rituximab for a broad array of disorders. Although several studies have explored the efficacy of other vaccines in rituximab-treated populations, results have been conflicting. We wished to define influenza vaccine efficacy in a rituximab-treated cohort. We examined 17 evaluable subjects treated with rituximab for rheumatologic conditions. T cell subsets, B cells subsets, T cell function, and B cell function were evaluated at specific time points along with hemagglutinination inhibition titers after receiving the standard inactivated influenza vaccine. T cell subset counts were significantly different than controls but did not change with rituximab. B cells depleted in all patients but were in various stages of recovery at the time of vaccination. Influenza vaccine responsiveness was poor overall, with only 16 % of subjects having a four-fold increase in titer. Pre-existing titers were retained throughout the study, however. The ability to respond to the influenza vaccine appeared to be related to the degree of B cell recovery at the time of vaccination. This study emphasizes that antibody responses to vaccine are impaired in subjects treated with rituximab and supports the concept that B cell recovery influences influenza vaccine responsiveness.
    Journal of Clinical Immunology 10/2012; · 3.38 Impact Factor
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    ABSTRACT: There are few data characterizing the immunologic consequences of chemotherapy for acute myeloid leukemia (AML) and almost nothing is known about the effects of chemotherapy in a pediatric AML cohort. We identified T-cell subsets, B-cell subsets, and used Enzyme-linked immunosorbent spot analyses to define the function of T cells and B cells in 7 pediatric patients with AML on chemotherapy. The data show that the effects of chemotherapy disproportionately target the B cell and depletion of B cells is associated with impaired responses to the inactivated influenza vaccine. Diminished T-cell numbers were also observed although the magnitude of the effect was less than what was seen for B cells. Furthermore, measures of T-cell function were largely intact. We conclude that humoral immunity is significantly affected by chemotherapy for AML.
    Journal of Pediatric Hematology/Oncology 09/2012; · 0.97 Impact Factor
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    ABSTRACT: In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Immunotherapy may have potential for consolidation therapy. This randomized open-label phase I/II trial evaluated responses of patients with advanced ovarian cancer in remission for vaccination with monocyte-derived dendritic cells (DC) loaded with Her2/neu, hTERT, and PADRE peptides, with or without low-dose intravenous cyclophosphamide. All patients also received pneumococcal vaccine and were randomized to cyclophosphamide 2 days prior to first vaccination. Blood samples were analyzed by ELISPOT and flow cytometry. Of 11 patients, 2 recurred during vaccination. Nine received all 4 doses: 3 patients recurred at 6, 17, and 26 months, respectively, and 6 have no evidence of disease at 36 months. No grade 3/4 vaccine-related toxicities were noted. The 3-year overall survival was 90%. Patients receiving cyclophosphamide showed a non-significant improvement in survival over controls. Patients receiving cyclophosphamide had a transient reduction in neutrophils, but no change in total lymphocytes or regulatory T cells. Modest T-cell responses to Her2/neu and hTERT were seen post-vaccine by IFN-γ ELISPOT. Patients demonstrated below normal responses to the diphtheria conjugate protein CRM197, a component of the pneumococcal vaccine. In this setting, peptide-loaded DC vaccination elicits modest immune responses, but survival is promising. Pneumococcal vaccination revealed substantial immune suppression, even in patients in remission. Rational design of consolidative strategies for ovarian cancer will need to overcome tolerance and immunosuppression.
    Cancer Immunology and Immunotherapy 10/2011; 61(5):629-41. · 3.64 Impact Factor
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    ABSTRACT: Prior to the advent of cardiac bypass, most children with congenital cardiac anomalies and chromosome 22q11.2 deletion syndrome died. With improved technology, there is now a wave of young adults with chromosome 22q11.2 deletion syndrome requiring clinical care. Fifteen young children and 20 adults with chromosome 22q11.2 deletion had flow cytometry, functional T cell analyses, and functional B cell analyses to characterize their immune system. Subjects were vaccinated with the annual inactivated influenza vaccine, and responses were evaluated by hemagglutination inhibition titer assessment. The pattern of T cell subset abnormalities was markedly different between pediatric and adult patients. In spite of the cellular deficits observed in adults, titers produced after influenza vaccine administration were largely intact. We conclude that disruption to T cell production appears to have secondary consequences for T cell differentiation and B cell function although the clinical impact remains to be determined.
    Journal of Clinical Immunology 08/2011; 31(6):927-35. · 3.38 Impact Factor
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    ABSTRACT: Severe immune deficiency follows autologous stem cell transplantation for multiple myeloma and is associated with significant infectious morbidity. This study was designed to evaluate the utility of a pretransplantation vaccine and infusion of a primed autologous T-cell product in stimulating specific immunity to influenza. Twenty-one patients with multiple myeloma were enrolled from 2007 to 2009. Patients were randomly assigned to receive an influenza-primed autologous T-cell product or a nonspecifically primed autologous T-cell product. The study endpoint was the development of hemagglutination inhibition titers to the strain-specific serotypes in the influenza vaccine. Enzyme-linked immunospot assays were performed to confirm the development of influenza-specific B-cell and T-cell immunity. Patients who received the influenza-primed autologous T-cell product were significantly more likely to seroconvert in response to the influenza vaccine (P = .001). Seroconversion was accompanied by a significant B-cell response. No differences were observed in the global quantitative recovery of T-cell and B-cell subsets or in global T-cell and B-cell function. The provision of a primed autologous T-cell product significantly improved subsequent influenza vaccine responses. This trial was registered at www.clinicaltrials.gov as #NCT00499577.
    Blood 01/2011; 117(1):63-71. · 9.78 Impact Factor
  • Gynecologic Oncology - GYNECOL ONCOL. 01/2011; 120.
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    ABSTRACT: While HIV-1-specific cellular immunity is thought to be critical for the suppression of viral replication, the correlates of protection have not yet been determined. Rhesus macaques (RM) are an important animal model for the study and development of vaccines against HIV/AIDS. Our laboratory has helped to develop and study DNA-based vaccines in which recent technological advances, including genetic optimization and in vivo electroporation (EP), have helped to dramatically boost their immunogenicity. In this study, RMs were immunized with a DNA vaccine including individual plasmids encoding SIV gag, env, and pol alone, or in combination with a molecular adjuvant, plasmid DNA expressing the chemokine ligand 5 (RANTES), followed by EP. Along with standard immunological assays, flow-based activation analysis without ex vivo restimulation and high-throughput gene expression analysis was performed. Strong cellular immunity was induced by vaccination which was supported by all assays including PBMC microarray analysis that identified the up-regulation of 563 gene sequences including those involved in interferon signaling. Furthermore, 699 gene sequences were differentially regulated in these groups at peak viremia following SIVmac251 challenge. We observed that the RANTES-adjuvanted animals were significantly better at suppressing viral replication during chronic infection and exhibited a distinct pattern of gene expression which included immune cell-trafficking and cell cycle genes. Furthermore, a greater percentage of vaccine-induced central memory CD8+ T-cells capable of an activated phenotype were detected in these animals as measured by activation analysis. Thus, co-immunization with the RANTES molecular adjuvant followed by EP led to the generation of cellular immunity that was transcriptionally distinct and had a greater protective efficacy than its DNA alone counterpart. Furthermore, activation analysis and high-throughput gene expression data may provide better insight into mechanisms of viral control than may be observed using standard immunological assays.
    PLoS ONE 01/2011; 6(6):e19681. · 3.53 Impact Factor
  • Gynecologic Oncology - GYNECOL ONCOL. 01/2011; 120.
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    Retrovirology 01/2009; · 5.66 Impact Factor
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    Retrovirology 01/2009; · 5.66 Impact Factor
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    Retrovirology 01/2009; 6. · 5.66 Impact Factor

Publication Stats

3k Citations
402.62 Total Impact Points

Institutions

  • 1997–2012
    • The Children's Hospital of Philadelphia
      • • Division of Oncology
      • • Department of Pediatrics
      Philadelphia, PA, United States
  • 1996–2012
    • University of Pennsylvania
      • • Perelman School of Medicine
      • • "Abramson" Cancer Center
      • • Department of Pathology and Laboratory Medicine
      Philadelphia, PA, United States
  • 1993–2012
    • Hospital of the University of Pennsylvania
      • • Department of Pathology and Laboratory Medicine
      • • Department of Medicine
      Philadelphia, Pennsylvania, United States
  • 2009
    • University of Washington Seattle
      • Department of Microbiology
      Seattle, Washington, United States
  • 2007
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
  • 1999
    • Drexel University
      • Department of Pediatrics
      Philadelphia, PA, United States
  • 1998
    • University of South Florida
      Tampa, Florida, United States
    • University of the Sciences in Philadelphia
      Philadelphia, Pennsylvania, United States
  • 1992
    • National Cancer Institute (USA)
      Maryland, United States