John J Treanor

University Center Rochester, Rochester, Minnesota, United States

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Publications (187)1491.7 Total impact

  • The Journal of infectious diseases. 09/2014;
  • The Journal of infectious diseases. 08/2014;
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    ABSTRACT: As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness.
    New England Journal of Medicine 08/2014; 371(7):635-45. · 51.66 Impact Factor
  • The Journal of infectious diseases. 06/2014;
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    ABSTRACT: The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza infection governs the antibody response thereafter. Subsequent influenza virus infections result in an antibody response against the original infecting virus, impairing the immune response against a newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans that had prior H1N1 infections with viruses of variable antigenic distance from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1-virus primed ferrets. Analysis of paired samples of human sera taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater fold-rise in antibody titer against the 2009 pH1N1 virus compared to H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.
    Clinical and vaccine Immunology: CVI 03/2014; · 2.60 Impact Factor
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    ABSTRACT: The emergence of avian H7N9 viruses in humans in China has renewed concerns about influenza pandemics emerging from Asia. Vaccines are still the best countermeasure against emerging influenza virus infections, but the process from identification of vaccine seed strains to the distribution of the final product can take several months. In the case of the 2009 H1N1 pandemic, a vaccine was not available before the first pandemic wave hit and therefore came too late to reduce influenza morbidity. H7 vaccines based on divergent isolates of the Eurasian and North American lineage have been tested in clinical trials, seed strains and reagents are already available and can potentially be used initially to curtail influenza-induced disease until a more appropriately matched H7N9 vaccine is ready. In a challenge experiment in the mouse model we assessed the efficacy of both inactivated virus and recombinant hemagglutinin vaccines made from seed strains that are divergent to H7N9 from each of each of the two major H7 lineages. Furthermore, we analyzed the cross-reactive responses to H7N9 of sera from human subjects vaccinated with heterologous North American and Eurasian lineage H7 vaccines. Vaccinations with inactivated virus and recombinant hemagglutinin protein preparations from both lineages raised hemagglutination-inhibiting antibodies against H7N9 viruses and protected mice from stringent viral challenges. Similar cross-reactivity was observed in sera of human subjects from a clinical trial with a divergent H7 vaccine. Existing H7 vaccine candidates based on divergent strains could be used as a first line of defense against an H7N9 pandemic. In addition it also suggests that H7N9 vaccines that are currently under development might be stockpiled and used for divergent avian H7 strains that emerge in the future.Importance Sporadic human infections with H7N9 viruses started being reported in China in early spring 2013. Despite a significant drop in infections during the summer months of 2013, an increased number of cases has already been reported for the 2013/14 winter season. The high case fatality rate, the ability to bind to receptors in the human upper respiratory tract in combination with several family clusters and the emergence of neuraminidase inhibitor resistant variants that show no loss of pathogenicity or ability to transmit in animal models have raised concerns about a potential pandemic and have spurred efforts to produce vaccine candidates. Here we show that antigens preparations from divergent H7 strains are able to induce protective immunity against H7N9 infection.
    Journal of Virology 01/2014; · 5.08 Impact Factor
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    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.
    Immunological investigations. 01/2014; 43(6):606-15.
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    Journal of Virological Methods. 01/2014; 206:156.
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    ABSTRACT: The estimation of the effectiveness of vaccination against seasonal influenza is guided by the comparison of antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in the vaccine. This study examined whether the prediction of antigenicity using sequence analysis of the hemagglutinin (HA) gene-encoded HA1-domain could be a simpler alternative to using the conventional hemagglutination inhibition (HI) assay, which requires influenza virus culturing. Specimens were taken from breakthrough cases that occurred in a trivalent influenza vaccine efficacy trial involving over 43000 participants during the 2008-2009 season. A total of 498 influenza viruses were successfully subtyped as A(H3N2) (380), A(H1N1) (29), B(Yamagata) (23) and B(Victoria) (66), from 603 PCR- or culture-confirmed specimens. Unlike the B-strain, most A(H3N2) (377) and all A(H1N1) viruses were designated as homologous to the respective vaccine strains based on the HA1-domain nucleic acid sequence. HI titers relative to the respective vaccine strains and PCR subtyping were determined for 48% (182/380) of A(H3N2) and 86% (25/29) of A(H1N1) viruses. Eighty-four percent of the A(H3N2) and A(H1N1) viruses designated as homologous by sequence were matched to the respective vaccine strains by HI testing. However, these homologous A(H3N2) and A(H1N1) viruses displayed a wide range of relative HI titers. Therefore, although PCR was a sensitive diagnostic method to confirm influenza cases, HA1 sequence analysis appeared to be of limited value in accurately predicting antigenicity and hence may be inappropriate to classify clinical specimens as homologous or heterologous to the vaccine-strain for estimating vaccine efficacy in a prospective clinical trial.
    Clinical and vaccine Immunology: CVI 12/2013; · 2.60 Impact Factor
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    ABSTRACT: Bacteriophage lambda capsids provide a flexible molecular scaffold that can be engineered to display a wide range of exogenous proteins, including full-length viral glycoproteins produced in eukaryotic cells. One application for such particles lies in the detection of virus-specific antibodies, since they may obviate the need to work with infectious stocks of highly pathogenic or emerging viruses that can pose significant biosafety and biocontainment challenges. Bacteriophage lambda capsids were produced that displayed an insect-cell derived, recombinant H5 influenza virus hemagglutinin (HA) on their surface. The particles agglutinated red blood cells efficiently, in a manner that could be blocked using H5 HA-specific monoclonal antibodies. The particles were then used to develop a modified hemagglutinination-inhibition (HAI) assay, which successfully identified human sera with H5 HA-specific HAI activity. These results demonstrate the utility of HA-displaying bacteriophage capsids for the detection of influenza virus-specific HAI antibodies.
    Journal of virological methods 12/2013; · 2.13 Impact Factor
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    ABSTRACT: Expression of recombinant hemagglutinin (rHA) in insect cells represents a technology with proven efficacy in seasonal influenza and with the potential for a rapid response to the emergence of new, pandemic strains. We evaluated the safety and immunogenicity of rHA vaccine (H5/Indonesia/5/05) produced in SF+ insect cells using a baculovirus expression vector system (BEVS). The rHA vaccine was tested with and without the adjuvant glucopyranosyl lipid A/stable emulsion (GLA/SE). Healthy adults 18-49 were randomized to two IM doses on Days 0 and 21 of placebo; unadjuvanted rHA 135μg or 45μg, or rHA 45μg, 15μg, 7.5μg or 3.8μg with GLA/SE. A pioneer group was monitored through Day 42 before randomizing remaining subjects. H5-specific antibody was determined by hemagglutination inhibition (HAI) and microneutralization (MN) on Days 0, 21 and 42. 392 subjects were randomized, of whom 380 (97%) received two doses and 386 (98%) completed 12 months of follow-up. Injection site pain and tenderness were seen in 50-70% of rHA+GLA/SE recipients and 4-9% of rHA alone and placebo recipients, but most complaints were mild to moderate in intensity. After two doses, the proportions of subjects with HAI titers ≥1:40 were 32% and 15% in the unadjuvanted 135μg and 45μg groups, and 82%, 75%, 66%, and 72% in those receiving 45μg, 15μg, 7.5μg, or 3.8μg with GLA/SE. The geometric mean titers (GMTs) of HAI antibody on Day 42 were 128, 95, 69, and 72 in the 45μg, 15μg, 7.5μg, or 3.8μg with GLA/SE groups, respectively. rHA GLA/SE was well tolerated and immunogenic in healthy adults, and GLA/SE substantially improved the serum antibody response. rHA expressed using BEVS recombinant DNA platform technology represents a promising strategy for pandemic control.
    Vaccine 09/2013; · 3.77 Impact Factor
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    ABSTRACT: Since the end of March 2013, avian a influenza viruses of the H7N9 subtype have caused more than 130 human cases of infection in China, many of which were severe, resulting in 43 fatalities. Although this A(H7N9) virus outbreak is now under control, the virus (or one with similar properties) could reemerge as winter approaches. To better assess the pandemic threat posed by A(H7N9) viruses, NIAID/NIH Centers of Excellence in Influenza Research and Surveillance (CEIRS) investigators and other expert laboratories in China and elsewhere have characterized the wild-type avian A(H7N9) viruses in terms of host range, virulence, and transmission, and are evaluating the effectiveness of antiviral drugs and vaccine candidates. However, to fully assess the potential risk associated with these novel viruses, there is a need for additional research including experiments that may be classified as "gain-of-function" (GOF). Here, we outline the aspects of the current situation that most urgently require additional research, our proposed studies, and risk-mitigation strategies.
    Science 08/2013; · 31.20 Impact Factor
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    ABSTRACT: BACKGROUND: Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. METHODS: This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. RESULTS: A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. CONCLUSION: In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses.
    Vaccine 05/2013; · 3.77 Impact Factor
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    ABSTRACT: The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses, but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18-32 years, 60-69 years, and ≥70 years. Day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater pre-vaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus-specific Ab-secreting cells and ≥4-fold increases in HAI and MN titers. However, the response was strongest in the 18-32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18-32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in anti-Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza.
    Clinical and vaccine Immunology: CVI 04/2013; · 2.60 Impact Factor
  • J J Treanor
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    ABSTRACT: Bison (Bison bison) and elk (Cervus elaphus) in the greater Yellowstone ecosystem have long been infected with Brucella abortus. The continued culling of large numbers of Yellowstone bison to reduce the risk of brucellosis transmission to cattle could negatively affect long-term conservation. A desirable management objective is to reduce the level of B. abortus infection while conserving wildlife populations. Identifying the ecological factors that influence immune suppression and vulnerabilityto infection will help initiate effective control measures. Seasonal food restriction during pregnancy has the potential to limit resources available for immune defence and may be an important factor sustaining brucellosis in wild ungulate populations. Consequently, effective management practices will need to include a diverse range of integrated methods, which include maintaining separation of livestock and wildlife, managing habitat to reduce brucellosis transmission, and reducing disease prevalence in wildlife. The long-term success of these management practices will depend on sound science and support of the stakeholders involved.
    Revue scientifique et technique (International Office of Epizootics) 04/2013; 32(1):239-47. · 0.69 Impact Factor
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    ABSTRACT: Eradication of brucellosis from bison (Bison bison) and elk (Cervus elaphus) populations in the Greater Yellowstone Area is not possible with current technology. There are considerable uncertainties regarding the effectiveness of management techniques and unintended effects on wildlife behaviour and demography. However, adaptive management provides a framework for learning about the disease, improving suppression techniques, and lowering brucellosis transmission among wildlife and to cattle. Since it takes approximately three years after birth for female bison to become reproductively active and contribute to brucellosis transmission, there is an opportunity to implement actions such as vaccination and the selective removal of infectious bison based on age and assay results to reduce the potential for transmission. Older adult bison that have been exposed to the bacteria, but recovered from acute infection, could be retained in the population to provide some immunity (resistance) against future transmission. Through careful predictions, research, and monitoring, our understanding and technology will be improved and management actions can be adjusted to better achieve desired outcomes.
    Revue scientifique et technique (International Office of Epizootics) 04/2013; 32(1):263-70. · 0.69 Impact Factor
  • John J Treanor, Peter Szilagyi
    Clinical Infectious Diseases 03/2013; · 9.37 Impact Factor
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    ABSTRACT: Broadly neutralizing antibodies directed against the conserved stalk domain of the viral hemagglutinin have attracted increasing attention in the recent years. However, only a limited number of stalk antibodies directed against group 2 influenza hemagglutinins have been isolated so far. Also, little is known about the general level of induction of these antibodies by influenza virus vaccination or infection. To characterize the anti-stalk humoral response in the mouse model as well as in humans, chimeric hemagglutinin constructs previously developed in our group were employed in serological assays. Whereas influenza virus infection induced high titers of stalk-reactive antibodies, immunization with inactivated influenza virus vaccines failed to do so in the mouse model. Analysis of serum samples collected from human individuals who were infected by influenza viruses also revealed the induction of stalk reactive antibodies. Finally, we show that the hemagglutinin-stalk directed antibodies induced in mice and humans have broad reactivity and neutralizing activity in vitro and in vivo. The results of the study point towards the existence of highly conserved epitopes in the stalk domains of group 2 hemagglutinins, which can be targeted for the development of a universal influenza virus vaccine in humans.
    Journal of Virology 02/2013; · 5.08 Impact Factor
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    ABSTRACT: BACKGROUND: Replication-competent virus vector vaccines might have advantages compared with non-replicating vector vaccines. We tested the safety and immunogenicity of an oral adenovirus serotype 4 vector vaccine candidate (Ad4-H5-Vtn) expressing the haemagglutinin from an avian influenza A H5N1 virus. METHODS: We did this phase 1 study at four sites in the USA. We used a computer-generated randomisation list (block size eight, stratified by site) to assign healthy volunteers aged 18-40 years to receive one of five doses of Ad4-H5-Vtn (10(7) viral particles [VP], 10(8) VP, 10(9) VP, 10(10) VP, 10(11) VP) or placebo (3:1). Vaccine or placebo was given on three occasions, about 56 days apart. Participants, investigators, and study-site personnel were masked to assignment throughout the study. Subsequently, volunteers received a boost dose with 90 μg of an inactivated parenteral H5N1 vaccine. Primary immunogenicity endpoints were seroconversion by haemagglutination-inhibition (HAI), defined as a four-times rise compared with baseline titre, and HAI geometric mean titre (GMT). We solicited symptoms of reactogenicity daily for 7 days after each vaccination and recorded symptoms that persisted beyond 7 days as adverse events. Primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01006798. FINDINGS: We enrolled 166 participants (125 vaccine; 41 placebo) between Oct 19, 2009, and Sept 9, 2010. HAI responses were low: 13 of 123 vaccinees (11%, 95% CI 6-17) and three of 41 placebo recipients (7%, 2-20) seroconverted. HAI GMT was 6 (95% CI 5-7) for vaccinees, and 5 (5-6) for placebo recipients. However, when inactivated H5N1 vaccine became available, one H5N1 boost was offered to all participants. In this substudy, HAI seroconversion occurred in 19 of 19 participants in the 10(11) VP cohort (100%; 95% CI 82-100) and eight of 22 placebo recipients (36%; 17-59); 17 of 19 participants in the 10(11) VP cohort (89%; 67-99) achieved seroprotection compared with four of 22 placebo recipients (18%; 5-40); GMT was 135 (89-205) with 10(11) VP, compared with 13 (7-21) with placebo. The cumulative frequency of abdominal pain, diarrhoea, and nasal congestion after all three vaccinations was significantly higher in vaccinees than placebo recipients (21 [16·8%] of 125 vs one [2·4%] of 41, p=0·017; 24 [19·2%] of 125 vs two [4·9%] of 41, p=0·027; 41 [32·8%] of 125 vs six [14·6%] of 41, p=0·028; respectively). No serious treatment-related adverse events occurred. INTERPRETATION: Oral Ad4 vector priming might enhance the efficacy of poorly immunogenic vaccines such as H5N1. FUNDING: Wellcome Trust Foundation, PaxVax.
    The Lancet Infectious Diseases 01/2013; · 19.97 Impact Factor
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    ABSTRACT: Human CD4 T cell recall responses to influenza virus are strongly biased towards Type 1 cytokines, producing IFNγ, IL-2 and TNFα. We have now examined the effector phenotypes of CD4 T cells in more detail, particularly focusing on differences between recent versus long-term, multiply-boosted responses. Peptides spanning the proteome of temporally distinct influenza viruses were distributed into pools enriched for cross-reactivity to different influenza strains, and used to stimulate antigen-specific CD4 T cells representing recent or long-term memory. In the general population, peptides unique to the long-circulating influenza A/New Caledonia/20/99 (H1N1) induced Th1-like responses biased toward the expression of IFNγ(+)TNFα(+) CD4 T cells. In contrast, peptide pools enriched for non-cross-reactive peptides of the pandemic influenza A/California/04/09 (H1N1) induced more IFNγ(-)IL-2(+)TNFα(+) T cells, similar to the IFNγ(-)IL-2(+) non-polarized, primed precursor T cells (Thpp) that are a predominant response to protein vaccination. These results were confirmed in a second study that compared samples taken before the 2009 pandemic to samples taken one month after PCR-confirmed A/California/04/09 infection. There were striking increases in influenza-specific TNFα(+), IFNγ(+), and IL-2(+) cells in the post-infection samples. Importantly, peptides enriched for non-cross-reactive A/California/04/09 specificities induced a higher proportion of Thpp-like IFNγ(-)IL-2(+)TNFα(+) CD4 T cells than peptide pools cross-reactive with previous influenza strains, which induced more Th1 (IFNγ(+)TNFα(+)) responses. These IFNγ(-)IL-2(+)TNFα(+) CD4 T cells may be an important target population for vaccination regimens, as these cells are induced upon infection, may have high proliferative potential, and may play a role in providing future effector cells during subsequent infections.
    PLoS ONE 01/2013; 8(3):e57275. · 3.73 Impact Factor

Publication Stats

7k Citations
1,491.70 Total Impact Points

Institutions

  • 1990–2014
    • University Center Rochester
      • • Department of Medicine
      • • Infectious Diseases Unit
      Rochester, Minnesota, United States
  • 2008–2013
    • National Park Service
      Washington, Washington, D.C., United States
    • Protein Sciences Corporation
      Meriden, Connecticut, United States
  • 1986–2013
    • University of Rochester
      • • School of Medicine and Dentistry
      • • Division of Infectious Diseases
      • • Department of Microbiology and Immunology
      • • Division of Hospital Medicine
      Rochester, New York, United States
  • 2012
    • Dartmouth Medical School
      • Department of Pediatrics
      Hanover, NH, United States
  • 2011
    • Colorado State University
      • Natural Resource Ecology Laboratory
      Fort Collins, CO, United States
  • 2010
    • Group Health Cooperative
      Seattle, Washington, United States
  • 2009
    • Novartis
      Bâle, Basel-City, Switzerland
    • Walter Reed National Military Medical Center
      Washington, Washington, D.C., United States
  • 2005–2008
    • Carnegie Mellon University
      • Department of Psychology
      Pittsburgh, PA, United States
  • 1990–2008
    • National Institute of Allergy and Infectious Diseases
      • • Laboratory of Parasitic Diseases (LPD)
      • • Laboratory of Immunoregulation
      Maryland, United States
  • 2006
    • United States Army Medical Research Institute for Infectious Diseases
      Maryland, United States
  • 2004
    • University of British Columbia - Vancouver
      • Department of Psychology
      Vancouver, British Columbia, Canada
  • 2001
    • Highland Hospital
      Oakland, California, United States
  • 2000
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 1998–2000
    • Saint Louis University
      • School of Medicine
      Saint Louis, MI, United States
  • 1996
    • University of Pennsylvania
      • Department of Pediatrics
      Philadelphia, PA, United States
  • 1995
    • Rochester General Hospital
      Rochester, New York, United States
  • 1989–1991
    • National Institutes of Health
      • Laboratory of Infectious Diseases
      Bethesda, MD, United States