Michal Mandelboim

Publications of Michal Mandelboim

• Vaccination against influenza in patients with systemic sclerosis.

  Authors: Ira Litinsky, Alexandra Balbir, Devy Zisman, Michal Mandelboim, Ella Mendelson, Joy Feld, Yolanda Braun, Marina Anouk, Ilana Kaufman, Daphna Paran, Dan Caspi, Ori Elkayam

  Clinical and experimental rheumatology. 03/2012;

  OBJECTIVES: To assess the efficacy and safety of the influenza virus vaccine in systemic sclerosis (SSc) patients compared to healthy controls. METHODS: Twenty-six SSc patients and 16 healthyOBJECTIVES: To assess the efficacy and safety of the influenza virus vaccine in systemic sclerosis (SSc) patients compared to healthy controls. METHODS: Twenty-six SSc patients and 16 healthy controls were vaccinated with a trivalent influenza subunit vaccine (H1N1 A/Brisbane/59/2007(TGA 2008/81B) (H1N1), H3N2 A/Uruguay/716/2007 (A/Brisbane/10/2007-like, NIBSC8/124) (H3N2) and B B/Brisbane/60/2008 (TGA 2009/82/B) (B)). The subjects were evaluated on the day of vaccination and 6 weeks later. Disease activity was assessed by the Rodnan score, number of ulcers, number of tender and swollen joints, the presence of dyspnea, cough, dyspepsia and dysphagia, and patient (PDAI) and physician (PHDAI) disease activity evaluation by the visual activity score (VAS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. The humoral response was evaluated by haemagglutination inhibition (HI). RESULTS: At baseline, 62%, 15% and 88% of the SSc patients had protective levels against H1N1, H3N2 and B, respectively, versus 56%, 62% and 87% for controls. Six weeks later, the proportion of responders to H1N1 was significantly higher in the SSc patients (73%) compared to controls (37.5%) (p=0.0225). The proportion of responders to H3N2 and B was similar in both groups, and both had a significant increase in geometric mean titers for each antigen. A lower response to H1N1 was associated with interstitial lung disease, while patients on combination calcium channel blockers and iloprost therapy showed significantly better response to H1N1 and B antigens. Most underlying disease activity parameters remained unchanged. CONCLUSIONS: The influenza virus vaccine was safe and generated a satisfactory humoral response in SSc patients.

• Increase Human Metapneumovirus Mediated Morbidity following Pandemic Influenza Infection.

  Authors: Liora Regev, Tal Meningher, Musa Hindiyeh, Ella Mendelson, Michal Mandelboim

  PloS one. 01/2012; 7(4):e34750.

  Human metapneumovirus (hMPV) is a recently discovered respiratory pathogen, infecting mainly young children. The infected patients suffer from influenza like symptoms (ILS). In Israel the virus isHuman metapneumovirus (hMPV) is a recently discovered respiratory pathogen, infecting mainly young children. The infected patients suffer from influenza like symptoms (ILS). In Israel the virus is mainly circulating in February to March. Here we report on an increased rate of hMPV infection in the winter season of 2009-10. The 2009-10 infection had several unique characteristics when compared to previous seasons; it started around January and a large number of infants were infected by the virus. Genetic analysis based on the viral L and F genes of hMPV showed that only subtypes A2 and B2 circulated in Israel. Additionally, we have identified a novel variant of hMPV within subgroup A2b, which subdivide it into A2b1 and A2b2. Finally, we showed that the hMPV infection was detected in the country soon after the infection with the pandemic influenza virus had declined, that infection with the pandemic influenza virus was dominant and that it interfered with the infection of other respiratory viruses. Thus, we suggest that the unusual increase in hMPV infection observed in 2009-10 was due to the appearance of the pandemic influenza virus in the winter season prior to 2009-10.

• Increased extent of and risk factors for pandemic (H1N1) 2009 and seasonal influenza among children, Israel.

  Authors: Dan Engelhard, Michal Bromberg, Diana Averbuch, Ariel Tenenbaum, Daniele Goldmann, Marina Kunin, Einat Shmueli, Ido Yatsiv, Michael Weintraub, Michal Mandelboim, Nurith Strauss-Liviatan, Emilia Anis, Ella Mendelson, Tamy Shohat, Dana G Wolf, Mervyn Shapiro, Itamar Grotto

  Emerging infectious diseases. 09/2011; 17(9):1740-3.

  During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. ChildrenDuring the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza.

• An outbreak of adenovirus type 7 in a residential facility for severely disabled children.

  Authors: Hammam Ghanaiem, Diana Averbuch, Benjamin Z Koplewitz, Ido Yatsiv, Jackues Braun, Natali Dehtyar, Dana G Wolf, Michal Mandelboim, Dan Engelhard

  The Pediatric infectious disease journal. 06/2011; 30(11):948-52.

  Adenoviruses cause a variety of clinical symptoms, involving the respiratory, gastrointestinal, urogenital, and neurologic systems. Only a few of the 55 known serotypes of adenovirus that affectAdenoviruses cause a variety of clinical symptoms, involving the respiratory, gastrointestinal, urogenital, and neurologic systems. Only a few of the 55 known serotypes of adenovirus that affect humans can cause outbreaks of respiratory tract infection. To describe the characteristics and clinical manifestations of severe respiratory disease contracted by 8 physically and cognitively disabled children during a very short outbreak of adenovirus serotype 7 infection in a residential facility. The clinical, imaging, and laboratory findings of the patients who were hospitalized with severe respiratory symptoms were retrospectively reviewed. Molecular typing of the adenovirus was performed. During 10 days in February 2010, 8 severely disabled children, 9 months to 5 years of age (median 22.5 months), from the same residential facility, were hospitalized due to severe acute respiratory disease with hypoxemia. Four of them (50%) needed mechanical ventilation for 2 to 8 days and one developed multisystem failure, including acute renal failure. Adenovirus serotype 7 was detected in the respiratory specimens of all 8 children. Two patients were treated with intravenous cidofovir. All 8 patients survived and were discharged after hospitalization of 6 to 15 (median: 11.5) days. The epidemiologic investigation revealed that all the 8 affected children shared a playroom and a caregiver worked with them while suffering fever, sore throat, and conjunctivitis before the onset of the outbreak. Adenovirus type 7 may cause short outbreaks of infection in institutions, causing children to develop life-threatening disease. Early detection of pathogens causing respiratory infections in institutions, isolation, and other preventive precautions are advocated. Moreover, vaccination of health care providers in institutions with the currently available live, oral adenovirus vaccine for types 4 and 7 should be considered.

• Influenza vaccination for terminally ill cancer patients receiving palliative care: a preliminary report.

  Authors: Menahem Sasson, Michal Mandelboim, Pesach Shvartzman

  Journal of pain and symptom management. 02/2011; 41(2):485-90.

  Cancer patients have impaired humoral and cellular immunity, and are more susceptible to infections; their immunological response is expected to be less effective than that of healthy people. ToCancer patients have impaired humoral and cellular immunity, and are more susceptible to infections; their immunological response is expected to be less effective than that of healthy people. To assess the immune response to influenza vaccine in terminally ill cancer patients in a home palliative care unit. During the fall of 2000-2001, 2005-2006, and 2006-2007, terminally ill cancer patients treated by our home palliative care unit were vaccinated against influenza with Vaxigrip(®). Blood samples were taken before and four weeks after vaccination. Influenza immunological response parameters accepted in the literature were calculated. Eighteen terminal cancer patients were vaccinated against influenza strains predicted for that year; 13 completed the study. The other five patients died within less than a month from the time of vaccination. The serum protection rate increased from 15.4% before to 61.5% after vaccination, and the serum response rate was 53.8% for all the three strains of vaccination. Mean-fold increase was 24.9 for influenza A-H1N1, 15.4 for influenza A-H3N2, and 2.8 for influenza B. Geometric mean titer was increased for influenza A-H3N2 from 8.3 before vaccination to 159.4 after vaccination; for influenza A-H1N1 from 5.2 to 124.3, and for influenza B from 5.7 to 44.6. The results indicate that influenza vaccination is probably effective and can be offered to terminally ill cancer patients with a life expectancy of about three months in a home care palliative care unit.

• Adenovirus infections in hospitalized patients in Israel: epidemiology and molecular characterization.

  Authors: Michal Mandelboim, Pnina Dror, Roberto Azar, Michal Bromberg, Ella Mendelson

  Journal of clinical microbiology. 02/2011; 49(2):597-601.

  Adenoviruses can cause a broad spectrum of clinical diseases, most of which are self-limited. However, adenovirus infection can occasionally result in severe or lethal infection. Fifty-fiveAdenoviruses can cause a broad spectrum of clinical diseases, most of which are self-limited. However, adenovirus infection can occasionally result in severe or lethal infection. Fifty-five adenovirus serotypes are known today, and they are classified into 7 subgroups (subgroups A to G). Here we examined 282 samples derived from hospitalized patients in Israel (September 2006 to August 2008) who were diagnosed as suffering from adenovirus infections. We used a recently described PCR amplification method and subsequent sequencing to identify the adenovirus. In addition, we studied the medical charts of 106 hospitalized patients from Sheba Medical Center in Israel. The most prevalent adenovirus serotypes found were serotypes 1 (22.8%), 2 (19.2%), 7 (18%), and 3 (14%). In addition, we identified several serotypes that have not been identified previously in Israel. Overall, serotypes of subgroup B were found to be approximately 4 times more prevalent among immunocompromised children than among generally healthy children (52.6%; P < 0.007). The realization that the virus subtypes are different among healthy and immunocompromised patients may lead to more efficient treatment of adenovirus infections among immunocompromised children in the future.

• Onset of a pandemic: characterizing the initial phase of the swine flu (H1N1) epidemic in Israel.

  Authors: Uri Roll, Rami Yaari, Guy Katriel, Oren Barnea, Lewi Stone, Ella Mendelson, Michal Mandelboim, Amit Huppert

  BMC infectious diseases. 01/2011; 11:92.

  The swine influenza H1N1 first identified in Mexico, spread rapidly across the globe and is considered the fastest moving pandemic in history. The early phase of an outbreak, in which data isThe swine influenza H1N1 first identified in Mexico, spread rapidly across the globe and is considered the fastest moving pandemic in history. The early phase of an outbreak, in which data is relatively scarce, presents scientific challenges on key issues such as: scale, severity and immunity which are fundamental for establishing sound and rapid policy schemes. Our analysis of an Israeli dataset aims at understanding the spatio-temporal dynamics of H1N1 in its initial phase. We constructed and analyzed a unique dataset from Israel on all confirmed cases (between April 26 to July 7, 2009), representing most swine flu cases in this period. We estimated and characterized fundamental epidemiological features of the pandemic in Israel (e.g. effective reproductive number, age-class distribution, at-risk social groups, infections between sexes, and spatial dynamics). Contact data collected during this stage was used to estimate the generation time distribution of the pandemic. We found a low effective reproductive number (Re=1.06), an age-class distribution of infected individuals (skewed towards ages 18-25), at-risk social groups (soldiers and ultra Orthodox Jews), and significant differences in infections between sexes (skewed towards males). In terms of spatial dynamics, the pandemic spread from the central coastal plain of Israel to other regions, with higher infection rates in more densely populated sub-districts with higher income households. Analysis of high quality data holds much promise in reducing uncertainty regarding fundamental aspects of the initial phase of an outbreak (e.g. the effective reproductive number Re, age-class distribution, at-risk social groups). The formulation for determining the effective reproductive number Re used here has many advantages for studying the initial phase of the outbreak since it neither assumes exponential growth of infectives and is independent of the reporting rate. The finding of a low Re (close to unity threshold), combined with identification of social groups with high transmission rates would have enabled the containment of swine flu during the summer in Israel. Our unique use of contact data provided new insights into the differential dynamics of influenza in different ages and sexes, and should be promoted in future epidemiological studies. Thus our work highlights the importance of conducting a comprehensive study of the initial stage of a pandemic in real time.

• Possible recurrent pandemic (H1N1) 2009 infection, Israel.

  Authors: Eran Kopel, Michal Mandelboim, Ziva Amitai, Itamar Grotto, Musa Hindiyeh, Ehud Kaliner, Ella Mendelson, Irina Volovik

  Emerging infectious diseases. 08/2010; 16(8):1321-2.

• Community-acquired oseltamivir-resistant pandemic (H1N1) 2009 in child, Israel.

  Authors: Zeev Zonis, Dan Engelhard, Musa Hindiyeh, Daniela Ram, Michal Mandelboim, Ella Mendelson, Daniel Glikman

  Emerging infectious diseases. 06/2010; 16(6):1045-6.

• Possible transmission of pandemic (HIN1) 2009 virus with oseltamivir resistance.

  Authors: Michal Mandelboim, Musa Hindiyeh, Tal Meningher, Ella Mendelson

  Emerging infectious diseases. 05/2010; 16(5):873-4.

• Development of oseltamivir resistance during oseltamivir therapy in a child with severe 2009 H1N1 influenza.

  Authors: Daniel Glikman, Zeev Zonis, Musa Hindiyeh, Musa Hindyieh, Daniela Ram, Michal Mandelboim, Ella Mendelson, Dan Engelhard

  The Pediatric infectious disease journal. 04/2010; 29(4):385-6.

• Killing of avian and Swine influenza virus by natural killer cells.

  Authors: Hagit Achdout, Tal Meningher, Shira Hirsh, Ariella Glasner, Yotam Bar-On, Chamutal Gur, Angel Porgador, Michal Mendelson, Michal Mandelboim, Ofer Mandelboim

  Journal of virology. 04/2010; 84(8):3993-4001.

  Today, global attention is focused on two influenza virus strains: the current pandemic strain, swine origin influenza virus (H1N1-2009), and the highly pathogenic avian influenza virus, H5N1. AtToday, global attention is focused on two influenza virus strains: the current pandemic strain, swine origin influenza virus (H1N1-2009), and the highly pathogenic avian influenza virus, H5N1. At present, the infection caused by the H1N1-2009 is moderate, with mortality rates of less <1%. In contrast, infection with the H5N1 virus resulted in high mortality rates, and ca. 60% of the infected patients succumb to the infection. Thus, one of the world greatest concerns is that the H5N1 virus will evolve to allow an efficient human infection and human-to-human transmission. Natural killer (NK) cells are one of the innate immune components playing an important role in fighting against influenza viruses. One of the major NK activating receptors involved in NK cell cytotoxicity is NKp46. We previously demonstrated that NKp46 recognizes the hemagglutinin proteins of B and A influenza virus strains. Whether NKp46 could also interact with H1N1-2009 virus or with the avian influenza virus is still unknown. We analyzed the immunological properties of both the avian and the H1N1-2009 influenza viruses. We show that NKp46 recognizes the hemagglutinins of H1N1-2009 and H5 and that this recognition leads to virus killing both in vitro and in vivo. However, importantly, while the swine H1-NKp46 interactions lead to the direct killing of the infected cells, the H5-NKp46 interactions were unable to elicit direct killing, probably because the NKp46 binding sites for these two viruses are different.

• Rapid detection of influenza A pandemic (H1N1) 2009 virus neuraminidase resistance mutation H275Y by real-time reverse transcriptase PCR.

  Authors: Musa Hindiyeh, Daniela Ram, Michal Mandelboim, Tal Meningher, Shira Hirsh, Jana Robinov, Virginia Levy, Sara Orzitzer, Roberto Azar, Zehava Grossman, Ella Mendelson

  Journal of clinical microbiology. 03/2010; 48(5):1884-7.

  The emergence of oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus highlights the need for rapid oseltamivir resistance screening. We report the development and validation ofThe emergence of oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus highlights the need for rapid oseltamivir resistance screening. We report the development and validation of high-throughput real-time reverse transcriptase PCR assays for the detection of the H275Y substitution in the neuraminidase 1 gene that can be accomplished in 3 to 4 h.

• NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus.

  Authors: Michal Mendelson, Yoram Tekoah, Alon Zilka, Orly Gershoni-Yahalom, Roi Gazit, Hagit Achdout, Nicolai V Bovin, Tal Meningher, Michal Mandelboim, Ofer Mandelboim, Ayelet David, Angel Porgador

  Journal of virology. 02/2010; 84(8):3789-97.

  Natural killer (NK) cells serve as a crucial first-line defense against tumors and virus-infected cells. We previously showed that lysis of influenza virus (IV)-infected cells is mediated by theNatural killer (NK) cells serve as a crucial first-line defense against tumors and virus-infected cells. We previously showed that lysis of influenza virus (IV)-infected cells is mediated by the interaction between the NK receptor, NKp46, and the IV hemagglutinin (HA) type 1 expressed by the infected cells. This interaction requires the presence of sialyl groups on the NKp46-T225 O-glycoforms. In the current study, we analyzed the O-glycan sequences that are imperative for the interaction between recombinant NKp46 (rNKp46) and IV H1N1 strains. We first showed that rNKp46 binding to IV H1N1 is not mediated by a glycoform unique to the Thr225 site. We then characterized the O-glycan sequences that mediate the interaction of rNKp46 and IV H1N1; we employed rNKp46s with dissimilar glycosylation patterns and IV H1N1 strains with different sialic acid alpha2,3 and alpha2,6 linkage preferences. The branched alpha2,3-sialylated O-glycoform Neu5NAcalpha2,3-Galbeta1,4-GlcNAcbeta1,6[Neu5NAcalpha2,3-Galbeta1,3]GalNAc competently mediated the interaction of rNKp46 with IV H1N1, manifesting a preference for alpha2,3 linkage. In contrast, the linear alpha2,3-sialylated O-glycoform Neu5NAcalpha2,3-Galbeta1,3-GalNAc was not correlated with enhanced interaction between rNKp46 and IV H1N1 or a preference for alpha2,3 linkage. The branched alpha2,3- and alpha2,6-sialylated O-glycoform Neu5NAcalpha2,3-Galbeta1,3[Neu5NAcalpha2,6]GalNAc competently mediated the interaction of rNKp46 with IV H1N1, manifesting a preference for alpha2,6 linkage. Previous viral HA-binding-specificity studies were performed with glycopolymer conjugates, free synthetic sialyl oligosaccharides, and sialidase-treated cells. This study shed light on the O-glycan sequences involved in the interaction of glycoprotein and viral hemagglutinins and may help in the design of agents inhibitory to hemagglutinin for influenza treatment.

• [Laboratory diagnosis of influenza H1N1 2009 at the Central Virology Laboratory in Israel during the first 12 weeks of the pandemic].

  Authors: Ella Mendelson, Michal Mandelboim, Zehava Grossman, Daniela Ram, Musa Hindiyeh

  Harefuah. 10/2009; 148(10):677-81, 735.

  Diagnosis of new emerging viruses in Israel is the responsibility of the Ministry of Health's Central Virology Laboratory (CVL). In April 2009, following the emergence of influenza H1N1 2009 virus inDiagnosis of new emerging viruses in Israel is the responsibility of the Ministry of Health's Central Virology Laboratory (CVL). In April 2009, following the emergence of influenza H1N1 2009 virus in Mexico and the WHO declaration of pandemia, the Israeli preparedness plan was launched. Development and application of a diagnostic test for H1N1 2009, diagnosis of cases in an outbreak setting and data analysis. In the absence of a validated test to detect the new strain of H1N1 2009, an RT-PCR amplification of a highly conserved matrix (M) gene of influenza A virus was employed. All positive PCR products were sequenced and compared to sequences in the GenBank. At a later stage, a specific kit provided by the WHO was used. Further improvements were introduced including "in-house" developed assays. Arrangements were made to allow around-the-clock testing of hundreds of samples without compromising other laboratory services. Between April 27th and mid July, 2809 samples were tested of which 1082 (38.5%) were positive. Most of the cases were found in the central part of Israel and around Jerusalem. The highest morbidity was in the 20-29 years age group, with the highest rate of positive cases in the 10-19 years age group. More males than females were ill. When a large outbreak of a novel infectious agent occurs, a supreme quality laboratory is essential. The Israel CVL made possible an early and prompt identification of H1N1 2009 from the outset and has met its ongoing challenges with a high degree of success.

• [Clinical and virological surveillance of influenza in Israel--implementation during pandemic influenza].

  Authors: Michal Bromberg, Zalman Kaufman, Michal Mandelboim, Hanna Sefty, Varda Shalev, Rachel Marom, Ella Mendelson, Manfred S Green, Tamy Shohat

  Harefuah. 09/2009; 148(9):577-82, 659.

  Pandemic influenza surveillance has a central role in providing an updated situation for the health care system. To describe the Israel Center for Disease Control (ICDC) pandemic influenzaPandemic influenza surveillance has a central role in providing an updated situation for the health care system. To describe the Israel Center for Disease Control (ICDC) pandemic influenza surveillance system. The ICDC conducts a seasonal influenza surveillance system based on patients' visits to community clinics (mainly Maccabi Healthcare Services) and emergency rooms for influenza-like illness (ILI) or pneumonia, and on laboratory confirmed nasopharyngeal swabs from ILI patients at designated sentinel clinics (tested at the Central Virology Laboratory). The laboratory based surveillance provides data on the active influenza strains, resistance to anti-viral drugs and match with the seasonal vaccine. The influenza surveillance network was strengthened since the level of the influenza pandemic alert was raised to phase 4 at the end of April 2009. The first A/H1N1 2009 cases were identified by the surveillance system in the last week of May 2009. Local transmission was recorded in the second half of June 2009. At this time there was an increase in the rates of patient visits to outpatient clinics for ILI, especially in the age group 0-18 years old and in residents of Tel Aviv, Central and Jerusalem districts. By the end of July 2009 there was an increase in pneumonia cases (mainly 2-18 years old) in community clinics. Once the pandemic influenza began spreading, the ICDC surveillance system provided a valid picture which facilitated the decision to stop laboratory confirmation of each community case and rely on the ICDC surveillance system as the main source for information.

• The Effect of Infliximab and Timing of Vaccination on the Humoral Response to Influenza Vaccination in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.

  Authors: Ori Elkayam, Amir Bashkin, Michal Mandelboim, Irena Litinsky, Doron Comaheshter, David Levartovsky, Ella Mendelson, Irena Wigler, Dan Caspi, Daphna Paran

  Seminars in arthritis and rheumatism. 02/2009;

  OBJECTIVES: To assess the effect of the timing of vaccination in relation to administration of infliximab on the efficacy and safety of influenza vaccine in patients with rheumatoid arthritis (RA)OBJECTIVES: To assess the effect of the timing of vaccination in relation to administration of infliximab on the efficacy and safety of influenza vaccine in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: The study population comprised 38 patients treated with infliximab at a mean dosage of 3 mg/kg (20 RA patients; 18 AS patients; 23 RA controls (treated with disease modifying antirheumatic drugs other than anti-tumor necrosis factor-alpha; and 17 healthy controls). Split-virion inactivated vaccine containing 15 mug hemagglutinin/dose of each of A/New Caledionan/20/1999 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (M) was used. Patients treated with infliximab were divided into 2 groups: 22 were vaccinated on the day of administration of infliximab, while 16 received the vaccine 3 weeks after infliximab. Baseline and 4- to 6-week clinical assessment of disease activity included erythrocyte sedimentation rate and C-reactive protein for all patients, the 28-joint disease-activity score for RA patients, and Bath Ankylosing Spondylitis Disease Activity Index for AS patients. Hemagglutination inhibition (HI) antibodies were tested by a standard World Health Organization procedure. Response was defined as >/=4-fold rise in HI antibodies 4 to 6 weeks after vaccination, or seroconversion in patients with a nonprotective baseline level of antibodies (<1/40). Geometric mean titers (GMT) were calculated to assess the immunity of the whole group. RESULTS: At baseline, RA patients and controls had similar occurrence of protective levels of HI antibodies and GMT, while AS patients had lower levels reflecting lower rates of previous vaccination. Four weeks after vaccination, a significant and similar increase in GMT for each antigen was observed in all groups (P < 0.004) except in the RA-infliximab group, vaccinated 3 weeks after administration of infliximab, in whom the increase in GMT was not significant for H1N1 (P = 0.12) and H3 (P = 0.06). AS patients demonstrated an increase in GMT, independently of the time of vaccination. The percentage of responders was similar in all groups. The response was not affected by variables such as age, gender, methotrexate, or prednisone use. Parameters of disease activity remained unchanged. No adverse effects other than injection site pain were recorded. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in RA and AS patients treated with infliximab.

• Adherence with oseltamivir chemoprophylaxis among workers exposed to poultry during avian influenza outbreaks in southern Israel.

  Authors: Ilana Belmaker, Michael Lyandres, Natalya Bilenko, Larissa Dukhan, Ella Mendelson, Michal Mandelboim, Liora Shahar-Rotberg, Einat Bitran, Yochi Yossef, Itamar Grotto

  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 11/2008;

  OBJECTIVES: To determine adherence with recommended pre- and post-exposure oseltamivir prophylaxis (OP) among workers exposed to poultry during five simultaneous avian influenza (AI) H5N1 outbreaksOBJECTIVES: To determine adherence with recommended pre- and post-exposure oseltamivir prophylaxis (OP) among workers exposed to poultry during five simultaneous avian influenza (AI) H5N1 outbreaks in poultry farms in southern Israel in March 2006, as well as the efficiency of the distribution system of oseltamivir in the community. DESIGN: Epidemiological investigation identified 201 workers exposed to poultry during AI outbreaks. They were interviewed by a public health nurse regarding adherence with recommended OP, symptoms, and possible side effects. Data were collected on type of exposure, age, sex, rate of adherence with OP, and reasons for non-adherence. For eight workers, paired sera were drawn for the determination of antibodies to H5. Data were collected on the efficiency of the distribution of oseltamivir tablets to workers in the community. RESULTS: High adherence with OP (87.6%) was found among poultry workers during outbreaks of AI, with no difference by type of exposure, age, or sex. There was a low rate of side effects of OP (1.5%). No exposed workers developed AI and none of the eight who had paired sera drawn showed seroconversion. The distribution of OP in the community was inefficient, with 27.7% of the tablets 'lost' or returned unusable. CONCLUSIONS: These data emphasize the importance of developing efficient targeted distribution systems in the community for OP, in order to prevent human infection during AI outbreaks.

• Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D.

  Authors: Noam Stern-Ginossar, Chamutal Gur, Moshe Biton, Elad Horwitz, Moran Elboim, Noa Stanietsky, Michal Mandelboim, Ofer Mandelboim

  Nature immunology. 10/2008; 9(9):1065-73.

  MICA and MICB are stress-induced ligands recognized by the activating receptor NKG2D. A microRNA encoded by human cytomegalovirus downregulates MICB expression by targeting a specific site in theMICA and MICB are stress-induced ligands recognized by the activating receptor NKG2D. A microRNA encoded by human cytomegalovirus downregulates MICB expression by targeting a specific site in the MICB 3' untranslated region. As this site is conserved among different MICB alleles and a similar site exists in the MICA 3' untranslated region, we speculated that these sites are targeted by cellular microRNAs. Here we identified microRNAs that bound to these MICA and MICB 3' untranslated region sequences and obtained data suggesting that these microRNAs maintain expression of MICA and MICB protein under a certain threshold and facilitate acute upregulation of MICA and MICB during cellular stress. These microRNAs were overexpressed in various tumors and we demonstrate here that they aided tumor avoidance of immune recognition.

• H5-type influenza virus hemagglutinin is functionally recognized by the natural killer-activating receptor NKp44.

  Authors: Joanna W Ho, Oren Hershkovitz, Malik Peiris, Alon Zilka, Ahuva Bar-Ilan, Beatrice Nal, Kid Chu, Mateusz Kudelko, Yiu-Wing Kam, Hagit Achdout, Michal Mandelboim, Ralf Altmeyer, Ofer Mandelboim, Roberto Bruzzone, Angel Porgador

  Journal of virology. 03/2008; 82(4):2028-32.

  Antiviral immune defenses involve natural killer (NK) cells. We previously showed that the NK-activating receptor NKp44 is involved in the functional recognition of H1-type influenza virus strains byAntiviral immune defenses involve natural killer (NK) cells. We previously showed that the NK-activating receptor NKp44 is involved in the functional recognition of H1-type influenza virus strains by NK cells. In the present study, we investigated the interaction of NKp44 and the hemagglutinin of a primary influenza virus H5N1 isolate. Here we show that recombinant NKp44 recognizes H5-expressing cells and specifically interacts with soluble H5 hemagglutinin. H5-pseudotyped lentiviral particles bind to NK cells expressing NKp44. Following interaction with target cells expressing H5, pseudotyped lentiviral particles, or membrane-associated H5, NK cells show NKp44-mediated induced activity. These findings indicate that NKp44-H5 interactions induce functional NK activation.