Roger S Geertsema

University of California, Irvine, Irvine, California, United States

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Publications (8)16.98 Total impact

  • Roger S. Geertsema · Claire E. Lindsell
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    ABSTRACT: When IVC are directly exhausted from a rodent housing room, the air quality of the room can become independent of the intracage air quality and may reduce the need for high room ventilation rates. This study assessed the effect of decreasing the ventilation rate in rodent rooms using direct-exhaust IVC systems. The study was conducted over 16 wk and compared conditions in 8 rodent rooms that had ventilation rates of 5 to 6 air changes per hour (ACH) with those in rooms at 10 to 12 ACH. At the low ventilation rate, rooms had higher CO2 concentrations, higher dew point temperature, and lower particulate levels and spent a greater percentage of time above the temperature set point than did rooms at the high rate. The levels of allergens and endotoxins in room air were the same regardless of the ventilation rate. Differences seen in parameters within cages at the 2 ventilation rates were operationally irrelevant. We detected no total volatile organic compounds in the room that were attributable to ammonia, regardless of the ventilation rate. Clearing the air of ethanol after a spill took longer at the low compared with high rate. However, ethanol clearance was faster at the low rate when the demand-control system was activated than at the high ventilation rate alone. Air quality in the room and in the cages were acceptable with room ventilation rates of 5 to 6 ACH in rodent rooms that use direct-exhaust IVC systems. Copyright © 2015 by the American Association for Laboratory Animal Science.
    No preview · Article · Sep 2015 · Journal of the American Association for Laboratory Animal Science: JAALAS
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    ABSTRACT: Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus type 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the therapeutic efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are mainly recognized by CD8(+) T cells from "naturally" protected HLA-A*02:01 positive, HSV-1 seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8(+) T cell epitopes (gD53-61, gD70-78 and gD278-286) were linked with a promiscuous CD4(+) T-cell epitope (gD287-317) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an N(ϵ)-palmitoyl-lysine moiety, a toll like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA-Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile PBS. The ASYMP therapeutic vaccination: (i) induced HSV-specific CD8(+) T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG); (ii) significantly reduced HSV-1 shedding detected in tears; (iii) boosted the number and function of HSV-1 gD epitopes-specific CD8(+) T cells in draining lymph nodes (DLN), conjunctiva, and TG; and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+)TIM-3(+)CD8(+) T-cells. The results underscore the potential of an ASYMP CD8(+) T cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. Seventy to 90% of adults harbor herpes simplex virus type 1 (HSV-1) infections, which it establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation resulting in viral shedding in tears. Most blinding herpetic disease in humans is due to reactivation of HSV-1 from latency rather than to primary acute infection. To date, there is no licensed therapeutic vaccine that can effectively stop or reduce HSV-1 reactivation from latently infected sensory ganglia and the subsequent shedding in tears. In the present study, we demonstrated that topical ocular therapeutic vaccination of latently infected HLA transgenic rabbits with a lipopeptide vaccine, that exclusively contains human "asymptomatic" CD8(+) T cell epitopes, successfully decreased spontaneous HSV-1 reactivation, as judged by a significant reduction in spontaneous shedding in tears. The findings should guide the clinical development of a safe and effective T-cell-based therapeutic herpes vaccine. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Apr 2015 · Journal of Virology
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    ABSTRACT: Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to <1% of eyes normally. All episodes of rHSK were preceded four to five days prior by an unusually large amount of reactivated virus in the tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4-5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4-5 days earlier.
    No preview · Article · Apr 2015 · Current eye research
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    ABSTRACT: Histophilus somni is a prevalent cause of pneumonia and septicemia in cattle. Yet evidence for protection against pneumonia by current vaccines is controversial. We have identified a new H. somni virulence factor, IbpA. Previous studies implicated three likely protective subunits or domains in IbpA (A3, A5, and DR2), which were expressed as recombinant GST fusion proteins and purified for systemic vaccination of calves. After two subcutaneous immunizations, calves were challenged intrabronchially with virulent H. somni strain 2336 and clinical signs were monitored for four days before necropsy. Serum samples were collected throughout. At necropsy, the area of gross pneumonia was estimated, bronchial lavage fluid was collected, lesions were cultured and tissue samples were fixed for histopathology. Results showed that calves immunized with IbpA DR2 had a statistically lower percentage of lung with gross lesions than controls, fewer histologic abnormalities in affected areas and no H. somni isolated from residual pneumonic lesions. Calves immunized with the control GST vaccine, IbpA3 or IbpA5 had larger H. somni positive pneumonic lesions. ELISA results for serum antibodies showed that calves immunized with the IbpA DR2 antigen had high IgG1 and IgG2 and lowest IgE responses to the immunizing antigen. Specific IgG responses were also high in the bronchial lavage fluid. High specific serum IgE responses were previously shown to be associated with more severe pneumonia, but high IgG specific anti-IbpA DR2 responses seem to be critically related to protection. Since the IbpA DR2 Fic motif has been shown to cause bovine alveolar cells to retract, we tested the neutralizing ability of pooled serum from the IbpA DR2 immunized group. This pooled serum reduced cytotoxicity by 75-80%, suggesting that the protection was due to antibody neutralization of IbpA cytotoxicity, at least in part. Therefore, IbpA DR2 appears to be an important protective antigen of H. somni. The study shows, for the first time, that immunization with a purified Fic protein protects against disease in a natural host.
    No preview · Article · Jun 2011 · Vaccine
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    ABSTRACT: Histophilus somni causes bovine pneumonia as well as septicemia and its sequelae but mechanisms of virulence and protective immunity are poorly understood. Since surface immunoglobulin binding proteins are virulence factors, we addressed their role as protective antigens in a mouse model of H. somni septicemia. Immunoglobulin binding protein A (IbpA), has homology to Bordetella pertussis filamentous hemagglutinin and other large bacterial exoproteins. IbpA is a major surface antigen encoded by the ibpA gene with many domains that may be important in pathogenesis and immune protection. Three IbpA recombinant protein subunits, IbpA3, IbpA5 and IbpADR2 were chosen for study because of putative functional domains and motifs. These recombinant GST fusion subunit proteins were compared with GST (negative control), formalin-killed H. somni (commercial vaccine control), live H. somni (to induce convalescent immunity) and H. somni culture supernatant (containing IbpA shed from the bacterial surface). In vaccination/challenge studies, both live H. somni (convalescent immunity) and supernatant protected equally but formalin-killed H. somni and GST did not protect against septicemia. The DR2 and A3 subunits protected moderately well and induced antibody responses against supernatant antigen and the homologous subunit in ELISA but not against whole cell antigens. Supernatant immunization protected better than the IbpA subunit antigens and induced high antibody activity against both whole cells and supernatant antigens. The results indicate that culture supernatant antigens or perhaps recombinant IbpA subunits may be useful in H. somni vaccines. These studies also provide insight into the contribution of IbpA domains to pathogenesis of H. somni septicemia.
    Full-text · Article · Jul 2008 · Vaccine

  • No preview · Article · Feb 2008 · Lab Animal
  • Roger S Geertsema · Richard A Kimball · Lynette B Corbeil
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    ABSTRACT: The role of bovine serum or plasma proteins in Haemophilus somnus virulence was investigated in a mouse model of septicemia. An increase in virulence was detected when the organism was pre-incubated for 5 min and inoculated with fetal calf serum. When purified bovine serum or plasma proteins were pre-incubated with H. somnus before inoculating into mice, transferrin was found to increase virulence. Bovine lactoferrin was also noted to increase virulence, but to a lesser extent and had a delayed time course when compared with transferrin. Using an ELISA assay, an increased amount of H. somnus whole cells and culture supernatant bound to bovine transferrin when the organism was grown in iron-restricted media. Lactoferrin also bound to H. somnus, but binding was not affected by growth in iron-restricted media and it was eliminated with 2M NaCl, which reversed charge mediated binding. Transferrin, but not lactoferrin, supported growth of H. somnus on iron-depleted agar based media using a disk assay. Therefore, lactoferrin increased virulence by an undetermined mechanism whereas transferrin increased virulence of H. somnus by binding to iron-regulated outer-membrane proteins (IROMPs) and providing iron to the pathogen.
    No preview · Article · Feb 2007 · Microbial Pathogenesis
  • R.S. Geertsema · C. Worby · R. Russo · D.S. Herdman · J. Dixon · L.B. Corbeil

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Publication Stats

32 Citations
16.98 Total Impact Points

Institutions

  • 2015
    • University of California, Irvine
      Irvine, California, United States
  • 2007-2011
    • University of California, San Diego
      • • Animal Care Program
      • • Department of Pathology
      San Diego, California, United States