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2. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Author

Abela, I., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Hachfeld, A., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Jackson-Perry, D., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Kusejko, K., Labhardt, N., Leuzinger, K., de Tejada B, Martinez, Marzolini, C., Metzner, K.J., Müller, N., Nemeth, J., Nicca, D., Notter, J., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Salazar-Vizcaya, L., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Wandeler, G., Weisser, M., Yerly, S., van der Valk, M., Geerlings, S.E., Goorhuis, A., Harris, V.C., Hovius, J.W., Lempkes, B., Nellen, F.J.B., van der Poll, T., Prins, J.M., Spoorenberg, V., van Vugt, M., Wiersinga, W.J., Wit, F.W.M.N., Bruins, C., van Eden, J., Hylkema-van den Bout, I.J., van Hes, A.M.H., Pijnappel, F.J.J., Smalhout, S.Y., Weijsenfeld, A.M., Back, N.K.T., Berkhout, B., Cornelissen, M.T.E., van Houdt, R., Jonges, M., Jurriaans, S., Schinkel, C.J., Wolthers, K.C., Zaaijer, H.L., Peters, E.J.G., van Agtmael, M.A., Autar, R.S., Bomers, M., Sigaloff, K.C.E., Heitmuller, M., Laan, L.M., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., van Arkel, A., Stohr, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., de Munnik, E.S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., van Eeden, A., Hoornenborg, E., Nellen, J., Alers, W., Elsenburg, L.J.M., Nobel, H., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., de Kruijf-van de Wiel, B.A.F.M., Adams, A., Rijkevoorsel, M. Pawels-van, Buiting, A.G.M., Murck, J.L., Rokx, C., Anas, A.A., Bax, H.I., van Gorp, E.C.M., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Schurink, C.A.M., Slobbe, L., de Vries-Sluijs, T.E.M.S., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., van Kampen, J.J.A., Koopmans, M.P.G., Rahamat-Langendoen, J.C., Branger, J., Douma, R.A., Cents-Bosma, A.S., Duijf-van de Ven, C.J.H.M., Schippers, E.F., van Nieuwkoop, C., Geilings, J., van Winden, S., van der Hut, G., van Burgel, N.D., Leyten, E.M.S., Gelinck, L.B.S., Mollema, F., Wildenbeest, G.S., Nguyen, T., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., van Hulzen, A.G.W., Kraan, S., Kruiper, M.S.M., van der Bliek, G.L., Bor, P.C.J., Debast, S.B., Wagenvoort, G.H.J., Roukens, A.H.E., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Scheper, H., Dorama, W., van Holten, N., Claas, E.C.J., Wessels, E., Hollander, J.G. den, El Moussaoui, R., Pogany, K., Brouwer, C.J., Heida-Peters, D., Mulder, E., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., Pontesilli, O., van Tienen, C., Lowe, S.H., Lashof, A.M.L. Oude, Posthouwer, D., van Wolfswinkel, M.E., Ackens, R.P., Burgers, K., Elasri, M., Schippers, J., Havenith, T.R.A., van Loo, M., van Vonderen, M.G.A., Kampschreur, L.M., van Broekhuizen, M.C., S, Faber, Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Wagenaar, J., Ruiter-Pronk, D., van Truijen-Oud, F.A., Stuart, J.W.T. Cohen, Hoogewerf, M., Rozemeijer, W., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Veenstra, J., Vrouenraets, S.M.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Knapen, M., Kok, M., van der Meché, I.B., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van de Laar, T.J.W., van Crevel, R., van Aerde, K., Dofferhoff, A.S.M., Henriet, S.S.V., Hofstede, H.J.M. ter, Hoogerwerf, J., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., McCall, M., Burger, D., Gisolf, E.H., Claassen, M., Hassing, R.J., Beest, G. ter, van Bentum, P.H.M., Gelling, M., Neijland, Y., Swanink, C.M.A., Velderman, M. Klein, van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Kalpoe, J.S., Wagemakers, A., Vahidnia, A., Lauw, F.N., Verhagen, D.W.M., van Wijk, M., Bierman, W.F.W., Bakker, M., van Bentum, R.A., van den Boomgaard, M.A., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Schenk, H.M., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., de Jonge, H., Maerman, M.M.M., de Weerd, D.A., van Eije, K.J., Knoester, M., van Leer-Buter, C.C., Niesters, H.G.M., T.Mudrikova, Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Hensgens, M.P.M., Oosterheert, J.J., Schadd, E.M., Verbon, A., van Welzen, B.J., Berends, H., Santen, B.M.G. Griffioen-van, de Kroon, I., Lunel, F.M. Verduyn, Wensing, A.M.J., Zaheri, S., Boyd, A.C., Bezemer, D.O., van Sighem, A.I., Smit, C., Hillebregt, M.M.J., Woudstra, T.J., Rutkens, T., Bergsma, D., Brétin, N.M., Lelivelt, K.J., van de Sande, L., van der Vliet, K.M. Visser.S.T., Paling, F., de Groot-Berndsen, L.G.M., van den Akker, M., Alexander, R., Bakker, Y., El Berkaoui, A., Bezemer-Goedhart, M., Djoechro, E.A., Groters, M., Koster, L.E., Lodewijk, C.R.E., Lucas, E.G.A., Munjishvili, L., Peeck, B.M., Ree, C.M.J., Regtop, R., van Rijk, A.F., Ruijs-Tiggelman, Y.M.C., Schnörr, P.P., Schoorl, M.J.C., Tuijn, E.M., Veenenberg, D.P., Witte, E.C.M., Bretin, N.M., Karpov, I., Losso, M., Lundgren, J., Rockstroh, J., Aho, I., Rasmussen, L.D., Novak, P., Pradier, C., Chkhartishvili, N., Matulionyte, R., Oprea, C., Kowalska, J.D., Begovac, J., Miró, J.M., Guaraldi, G., Paredes, R., Peters, L., Larsen, J.F., Neesgaard, B., Jaschinski, N., Fursa, O., Raben, D., Kristensen, D., Fischer, A.H., Jensen, S.K., Elsing, T.W., Gardizi, M., Mocroft, A., Phillips, A., Reekie, J., Cozzi-Lepri, A., Pelchen-Matthews, A., Roen, A., Tusch, E.S., Bannister, W., Bellecave, P., Blanco, P., Bonnet, F., Bouchet, S., Breilh, D., Cazanave, C., Desjardin, S., Gaborieau, V., Gimbert, A., Hessamfar, M., Lacaze-Buzy, L., Lacoste, D., Lafon, M.E., Lazaro, E., Leleux, O., Le Marec, F., Le Moal, G., Malvy, D., Marchand, L., Mercié, P., Neau, D., Pellegrin, I., Perrier, A., Petrov-Sanchez, V., Vareil, M.O., Wittkop, L., Bernard, N., Chaussade, D. Bronnimann H., Dondia, D., Duffau, P., Faure, I., Morlat, P., Mériglier, E., Paccalin, F., Riebero, E., Rivoisy, C., Vandenhende, M.A., Barthod, L., Dauchy, F.A., Desclaux, A., Ducours, M., Dutronc, H., Duvignaud, A., Leitao, J., Lescure, M., Nguyen, D., Pistone, T., Puges, M., Wirth, G., Courtault, C., Camou, F., Greib, C., Pellegrin, J.L., Rivière, E., Viallard, J.F., Imbert, Y., Thierry-Mieg, M., Rispal, P., Caubet, O., Ferrand, H., Tchamgoué, S., Farbos, S., Wille, H., Andre, K., Caunegre, L., Gerard, Y., Osorio-Perez, F., Chossat, I., Iles, G., Labasse-Depis, M., Lacassin, F., Barret, A., Castan, B., Koffi, J., Rouanes, N., Saunier, A., Zabbe, J.B., Dumondin, G., Beraud, G., Catroux, M., Garcia, M., Giraud, V., Martellosio, J.P., Roblot, F., Pasdeloup, T., Riché, A., Grosset, M., Males, S., Bell, C. Ngo, Carpentier, C., Bellecave, Virology P., Tumiotto, C., Miremeont-Salamé, G., Arma, D., Arnou, G., Blaizeau, M.J., Camps, P., Decoin, M., Delveaux, S., Diarra, F., Gabrea, L., Lawson-Ayayi, S., Lenaud, E., Plainchamps, D., Pougetoux, A., Uwamaliya, B., Zara, K., Conte, V., Gapillout, M., Surial, Bernard, Ramírez Mena, Adrià, Roumet, Marie, Limacher, Andreas, Smit, Colette, Leleux, Olivier, Mocroft, Amanda, van der Valk, Marc, Bonnet, Fabrice, Peters, Lars, Rockstroh, Jürgen K., Günthard, Huldrych F., Berzigotti, Annalisa, Rauch, Andri, and Wandeler, Gilles

Published
2023
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4. Intradermal hepatitis B vaccination in non-responders after topical application of imiquimod (Aldara®)

Author

Roukens, Anna H., Vossen, Ann C., Boland, Greet J., Verduyn, Willem, van Dissel, Jaap T., and Visser, Leo G.

Subjects
*HEPATITIS B vaccines, *VIRAL vaccines, *IMMUNOCOMPETENT cells, *IMMUNE response, *CLINICAL trials, *DRUG administration, *IMMUNOGLOBULINS, *DRUG efficacy
Abstract

Abstract: Trial registration: NTR1043 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1043). Background: Five to ten percent of immunocompetent persons fail to develop a protective immune response to hepatitis B vaccination, and are defined non-responders (NR). We investigated the immune response to intradermal hepatitis B vaccination after pre-treatment of the skin with the TLR7 agonist imiquimod. Methods: Twenty-one non-responders (anti-HBs <10IU/l after at least 6 intramuscular hepatitis B vaccinations) were randomly assigned to the control group (N =11) or the experimental group (N =10). Participants in both groups received 3 intradermal (ID) vaccinations with 5μg HBsAg (0.125mL) at 0, 1 and 6 months. In the experimental group, the dermal site of injection was pre-treated with 250mg imiquimod ointment. Anti-HBs antibodies were determined at 0, 1, 2, 6 and 7 months. Results: In both study groups, 70% of the participants developed a protective immune response (anti-HBs ≥10IU/l), after the 3rd intradermal vaccination. Conclusion: The application of imiquimod on the skin prior to intradermal vaccination did not enhance the humoral response to hepatitis B vaccine. However, irrespective of imiquimod application, 70% of the NR who had not responded to 6 previous intramuscular vaccinations, developed a protective immune response with high affinity antibodies after 3 ID hepatitis B vaccinations with 5μg HBsAg. [Copyright &y& Elsevier]

Published
2010
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5. Reduced dose pre-exposure primary and booster intradermal rabies vaccination with a purified chick embryo cell vaccine (PCECV) is immunogenic and safe in adults

Author

Roukens, A.H., Vossen, A.C., van Dissel, J.T., and Visser, L.G.

Subjects
*VACCINATION, *PREVENTIVE medicine, *VIRUS diseases, *IMMUNIZATION
Abstract

Abstract: Pre-exposure vaccination of persons at risk with intradermally administered reduced dose cell culture rabies vaccines remains controversial in low-enzootic countries. In a prospective clinical trial of adult volunteers (N =25), we studied the immune response to purified chick embryo cell vaccine (PCECV) administered intradermally at a reduced dose (0.1mL) in a three-dose schedule (0, 7 and 21 days). In 10 subjects, immunogenicity of intradermally administered one-dose booster vaccination with 0.1mL PCECV was investigated. All participants were seroconverted 3 weeks after primary and 1 week after booster vaccination (antibody titre ≥0.5EU/mL, measured by enzyme linked immunosorbent assay). Local adverse events such as erythema and swelling were moderate and transitory. The intradermal vaccination route offers an efficacious and cost-reducing strategy to increase the accessibility of cell culture rabies vaccines. [Copyright &y& Elsevier]

Published
2008
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6. Reduced intradermal test dose of yellow fever vaccine induces protective immunity in individuals with egg allergy

Author

Roukens, Anna H., Vossen, Ann C., van Dissel, Jaap T., and Visser, Leo G.

Subjects
*YELLOW fever vaccines, *INTRADERMAL injections, *VIRAL vaccines, *CELLULAR immunity, *DRUG dosage, *FOOD allergy, *EGGS, *VIRAL antibodies, *SKIN tests, *DRUG side effects
Abstract

Abstract: The neutralising antibody response after the yellow fever vaccine (YF-17D) skin test was measured in 7 egg allergic persons in whom further vaccination was abandoned because of a strong local urticarial reaction to the YF-17D vaccine test dose. We found that this test dose of 0.1mL of YF-17D vaccine was sufficient to induce a protective antibody response in all 7 subjects. Intradermal injection of 1/5th dose of the yellow fever vaccine appears to be sufficient, in non-allergic as well as allergic persons, and non-inferior to the subcutaneous full dose. [Copyright &y& Elsevier]

Published
2009
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7. A comparison of two Fendrix hepatitis B vaccination schedules in patients with inflammatory bowel disease.

Author

Kuiper, Vincent P., van der Plas, Pauline, Hoogerwerf, Marie-Astrid, Pieter R. Koopman, Jan, van der Meulen, Andrea E., Roukens, Anna H.E., Visser, Leo G., and Roestenberg, Meta

Subjects
*HEPATITIS B vaccines, *BOOSTER vaccines, *HEPATITIS B, *HEPATITIS B virus, *INFLAMMATORY bowel diseases
Abstract

Systemic immunosuppressive therapy (IS) renders patients with inflammatory bowel disease (IBD) vulnerable to fulminant hepatitis B virus (HBV) infection. Seroprotection against HBV through a full vaccination scheme is preferably obtained before IS is initiated, but often conflicts with the clinical need to initiate therapy rapidly. Consequently, the vast majority of patients will use IS during booster vaccinations. In this retrospective cohort study, we examined the serological response after a modified vaccination schedule which includes an initial double dose of Fendrix in patients with IBD and compared the results with the serological responses of patients with IBD who received the standard schedule. Seroprotection rates were 86.2 % and 88.9 % in the modified and standard schedule groups respectively. One-third of patients obtained seroprotection after only one double dose vaccine. A double dose may be considered in patients with IBD at high short-term risk of HBV infection when a rapid protective response is warranted. [ABSTRACT FROM AUTHOR]

Published
2022
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8. Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.

Author

ten Doesschate, Thijs, van der Vaart, Thomas W., Debisarun, Priya A., Taks, Esther, Moorlag, Simone J.C.F.M., Paternotte, Nienke, Boersma, Wim G., Kuiper, Vincent P., Roukens, Anna H.E., Rijnders, Bart J.A., Voss, Andreas, Veerman, Karin M., Kerckhoffs, Angele P.M., Oever, Jaap ten, van Crevel, Reinout, van Nieuwkoop, Cees, Lalmohamed, Arief, van de Wijgert, Janneke H.H.M., Netea, Mihai G., and Bonten, Marc J.M.

Subjects
*MEDICAL personnel, *PANDEMICS, *COVID-19 pandemic, *RANDOMIZED controlled trials, *COVID-19, *BCG vaccines, *FEVER
Abstract

The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78–1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72–1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99–1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19. [ABSTRACT FROM AUTHOR]

Published
2022
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9. Intradermal fractional dose vaccination as a method to vaccinate individuals with suspected allergy to mRNA COVID-19 vaccines.

Author

Roozen, Geert V.T., Granger, Alexandra, van Binnendijk, Rob S., den Hartog, Gerco, Roestenberg, Meta, Visser, Leo G., and Roukens, Anna H.E.

Subjects
*VACCINATION status, *COVID-19 vaccines, *SKIN tests, *ANAPHYLAXIS, *ANTIBODY formation, *IMMUNOGLOBULINS
Abstract

Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who had experienced possible allergic symptoms after their first intramuscular dose of a COVID-19 mRNA vaccine with a 1/5th fractional intradermal test dose of the mRNA-1273 (Moderna) COVID-19 vaccine. No anaphylactic reactions were observed after intradermal vaccination (n = 56). Serum anti-S1 IgG concentrations were measured using a bead-based multiplex assay four weeks after vaccinations. Antibody concentrations were compared with a previously collected nationwide cohort that had received two intramuscular doses of mRNA-1273. Antibody responses in all subjects tested (n = 47) were comparable to standard of care intramuscular dosing. Fractional intradermal dosing of mRNA COVID-19 vaccines may provide a pragmatic solution that is safe, time efficient compared to skin prick testing, dose sparing and immunogenic in individuals with suspected vaccine allergy. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Serological response to three alternative series of hepatitis B revaccination (Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders: a multicentre, open-label, randomised, controlled, superiority trial.

Author

Raven, Stijn F H, Hoebe, Christian J P A, Vossen, Ann C T M, Visser, Leo G, Hautvast, Jeannine L A, Roukens, Anna H E, and van Steenbergen, Jim E

Subjects
*HEPATITIS B, *HEPATITIS B vaccines, *PUBLIC health, *HERPES zoster, *HEPATITIS B prevention, *RESEARCH, *IMMUNIZATION, *HEPATITIS A vaccines, *RESEARCH methodology, *EVALUATION research, *MEDICAL cooperation, *COMBINED vaccines, *COMPARATIVE studies, *RANDOMIZED controlled trials, *VIRAL antibodies, *STATISTICAL sampling
Abstract

Background: Serological non-response can be present after hepatitis B vaccination in healthy adults. We aimed to establish which of three revaccination regimens is most effective at inducing protective immunity METHODS: Healthy adults (aged 18-80 years) from 16 Dutch centres (13 public health services, two university hospitals, and one travel clinic) were included in this multicentre, parallel group, randomised, controlled, superiority trial. The inclusion criterion was vaccine non-response (hepatitis B surface antibody [anti-HBs] titre <10 IU/L) after a primary series with three doses of one type of recombinant vaccine against hepatitis B virus (either HBVaxPro-10 or Engerix-B at months 0, 1, and 6). Participants were individually randomly assigned (1:1:1:1) to a vaccination series of repeated initial vaccination (HBVaxPro 10 μg or Engerix-B 20 μg) as the control, or to Twinrix 20 μg, Fendrix 20 μg, or HBVaxPro 40 μg. We used a web-based randomisation programme, stratified by centre, with a block size of four. Participants and centres were unmasked to assignment after randomisation. Laboratory staff and investigators were masked to vaccine-group assignment. All revaccination schedules were identical, with intramuscular vaccinations at 0, 1, and 2 months. Anti-HBs was measured at 0, 1, 2, and 3 months. The primary outcome was the percentage of responders (anti-HBs titres ≥10 IU/L) at 3 months. Immunogenicity and safety analyses were based on an intention-to-vaccinate analysis, the immunogenicity analysis with last observation carried forward for missing data, and the Bonferroni and the Benjamini-Hochberg method were applied to correct for multiple testing. The trial was registered in the Dutch National Trial Register and inclusion has been stopped (identifier NL3011; EudraCT-number 2011-005627-40).Findings: The participants were recruited between Nov 1, 2012, and Sept 1, 2017. 480 participants were randomly assigned and included in intention-to-vaccinate analyses: 124 (26%) to control, 118 (25%) to Twinrix, 114 (24%) to HBVaxPro-40, and 124 (26%) to Fendrix. At month 3 the percentage of responders was 83 (67%) of 124 (95% CI 57·9-75·1 in the control group, 94 (80%) of the 118 (71·3-86·5) in the Twinrix group, 95 (83%) of 114 (75·2-89·7) in the HBVaxPro-40 group, and 108 (87%) of 124 (79·9-92·4) in the Fendrix group. Compared with the control group, the percentage of responders was superior for the HBVaxPro-40 group (adjusted difference 21·6% [95% CI 10·4-32·7], p=0·0204 [Bonferroni corrected p value]) and the Fendrix group (26·3% [15·4-37·3], p=0·0006), but not the Twinrix group (25·0% [13·0-37·0]; p=0·0846). One serious adverse event occurred (herpes zoster ophthalmicus) in the Fendrix group, which was not attributed to the vaccine.Interpretation: Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders.Funding: National Institute for Public Health and the Environment. [ABSTRACT FROM AUTHOR]

Published
2020
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13. Dendritic Cells Expand Epstein Barr Virus Specific CD8+ T Cell Responses More Efficiently Than EBV Transformed B Cells

Author

Subklewe, Marion, Sebelin, Kathrin, Block, Andrea, Meier, Antje, Roukens, Anna, Paludan, Casper, Fonteneau, Jean-François, Steinman, Ralph M., and Münz, Christian

Subjects
*DENDRITIC cells, *LYMPHOPROLIFERATIVE disorders, *CELL proliferation, *CELL lines
Abstract

Abstract: Adoptive transfer of Epstein Barr virus (EBV) specific cytotoxic T lymphocytes (CTLs) has been successfully applied in the treatment of EBV associated post-transplant lymphoproliferative disease (PTLD). In most studies EBV transformed B cells (LCLs) have been used for the induction of EBV specific T cell lines. Application of this approach to other EBV associated tumors is difficult, because LCLs focus T cell expansion toward immunodominant EBV antigens that are not expressed in EBV associated Hodgkin’s lymphoma and nasopharyngeal carcinoma. Therefore, we compared dendritic cells (DCs) with LCLs for CD8+ T cell stimulation against dominant and subdominant EBV antigens. DCs expanded tenfold more EBNA3A and LMP2 specific CD8+ T cells than LCL and also stimulated EBV specific CTL from PTLD patients. Both, DCs and LCLs stimulations led to the expansion of high affinity T cells, capable to target EBV transformed B cells. While LCLs and DCs expressed MHC class I and II products at similar levels, DCs showed a higher expression of costimulatory and adhesion molecules. This resulted in more efficient T cell conjugate formation with DCs than with LCLs. We propose the use of DCs for stimulaton of EBV specific T cells in active or passive immunotherapy of EBV associated malignancies. [Copyright &y& Elsevier]

Published
2005
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