42 results on '"Mann, Philipp"'
Search Results
2. Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial
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Allagappen, Jon, Andriesen, Jessica, Ayres, Alison, Bekker, Linda-Gail, Borremans, Caroline, Brumskine, William, Chilengi, Roma, Dubula, Thozama, Garrett, Nigel, Gelderblom, Huub, Gill, Katherine, Hoosain, Zaheer, Hosseinipour, Mina, Hutter, Julia, Inambao, Mubiana, Innes, Craig, Kilembe, William, Kotze, Philippus, Kotze, Sheena, Laher, Fatima, Laszlo, Imre, Lazarus, Erica, Malahleha, Mookho, Mathebula, Matsontso, Matoga, Mitch, McClennen, Rachael, Mda, Pamela, Meerts, Peter, Naicker, Vimla, Naidoo, Logashvari, Philip, Tricia, Pitsi, Annah, Scheppler, Lorenz, Sopher, Carrie, Takuva, Simbarashe G., Viegas, Edna, Weijtens, Mo, Yuan, Olive, Gray, Glenda E, Mngadi, Kathryn, Lavreys, Ludo, Nijs, Steven, Gilbert, Peter B, Hural, John, Hyrien, Ollivier, Juraska, Michal, Luedtke, Alex, Mann, Philipp, McElrath, M Juliana, Odhiambo, Jackline A, Stieh, Daniel J, van Duijn, Janine, Takalani, Azwidihwi N, Willems, Wouter, Tapley, Asa, Tomaras, Georgia D, Van Hoof, Johan, Schuitemaker, Hanneke, Swann, Edith, Barouch, Dan H, Kublin, James G, Corey, Lawrence, Pau, Maria G, Buchbinder, Susan, and Tomaka, Frank
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- 2024
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3. Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: A phase 2 randomized study
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Sáez-Llorens, Xavier, Lanata, Claudio, Aranguren, Elaine, Celis, Carlos R., Cornejo, Rubelio, DeAntonio, Rodrigo, Ecker, Lucie, Garrido, Diegi, Gil, Ana I., Gonzales, Marina, Hess-Holtz, Morgan, Leroux-Roels, Geert, Junker, Helga, Kays, Sarah-Katharina, Koch, Sven D., Lazzaro, Sandra, Mann, Philipp, Quintini, Gianluca, Srivastava, Barkha, Vahrenhorst, Dominik, von Eisenhart-Rothe, Philipp, Wolz, Olaf-Oliver, and Oostvogels, Lidia
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- 2022
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4. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial
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Lovesio, Luciano, Diez, Fabián, Grazziani, Franco, Ganaha, Maria Cristina, Zalatnik, Viviana Judith, Dittrich, Ricardo Julio, Espínola, Lidia, Lambert, Sandra, Longhi, Andrea, Vecchio, Claudia, Mastruzzo, María, Fernandez, Alberto, Borchowiek, Silvina, Potito, Roberto, Ahuad Guerrero, Rodolfo Andres, Guardiani, Fernando Martin, Castella, Sofia, Foccoli, Monica, Pedernera, Aldana, Braida, Ariel, Durigan, Virginia, Martella, Carolina, Bobat, Antonela, Boggia, Bruno Emilio, Nemi, Sergio Andrés, Tartaglione, Javier Gerardo, Piedimonte, Fabián César, De Bie, Jessie, Reynales Londoño, Humberto, Rodríguez Ordoñez, Paula Andrea, García Cruz, Johanna Marcela, Bautista Toloza, Leonardo, Ladino González, Margot Cecilia, Zambrano Ochoa, Adriana Pilar, Prieto Pradera, Iñigo, Torres Hernandez, Daniela, Mazo Elorza, Diana Patricia, Collazos Lennis, Maria Fernanda, Vanegas Dominguez, Beatriz, Solano Mosquera, Lina Marianur, Fendel, Rolf, Fleischmann, Wim Alexander, Koehne, Erik, Kreidenweiss, Andrea, Köhler, Carsten, Esen, Meral, Horn, Carola, Eberts, Sandra, Kroidl, Arne, Huber, Kristina, Thiel, Verena, Mazara Rosario, Sonia, Reyes, Gilda, Rivera, Laura, Donastorg, Yeycy, Lantigua, Flavia, Torres Almanzar, Dania, Candelario, Rosalba, Peña Mendez, Lourdes, Rosario Gomez, Nadia, Portolés-Pérez, Antonio, Ascaso del Río, Ana, Laredo Velasco, Leonor, Bustinduy Odriozola, Maria Jesus, Larrea Arranz, Igor, Martínez Alcorta, Luis Ignacio, Durán Laviña, María Isabel, Imaz-Ayo, Natale, Meijide, Susana, García-de-Vicuña, Aitor, Santorcuato, Ana, Gallego, Mikel, Aguirre-García, Gloria Mayela, Olmos Vega, Jocelyn, González Limón, Pablo, Vázquez Villar, Andrea, Chávez Barón, Jaime, Arredondo Saldaña, Felipe, Luján Palacios, Juan de Dios, Camacho Choza, Laura Julia, Vázquez Saldaña, Eduardo Gabriel, Ortega Dominguez, Sandra Janeth, Vega Orozco, Karen Sofia, Torres Quiroz, Ivonne Aimee, Martinez Avendaño, Alejandro, Herrera Sanchez, Javier, Guzman, Esperanza, Castro Castrezana, Laura, Ruiz Palacios y Santos, Guillermo Miguel, de Winter, Ronald Frank Jacobus, de Jonge, Hanna K, Schnyder, Jenny L, Boersma, Wim, Hessels, Lisa, Djamin, Remco, van der Sar, Simone, DeAntonio, Rodrigo, Peña, Moisés, Rebollon, Gabriel, Rojas, Marianela, Escobar, Johnny, Hammerschlag Icaza, Bruno, Wong T, Digna Y, Barrera Perigault, Paulo, Ruiz, Sergio, Chan, Milagros, Arias Hoo, Dommie Janneth, Gil, Ana I, Celis, Carlos R, Balmaceda, Maria Pia, Flores, Omar, Ochoa, Mayra, Peña, Bia, de la Flor, Carolina, Webb, Camille María, Cornejo, Enrique, Sanes, Fatima, Mayorga, Valerie, Valdiviezo, Gladys, Ramírez Lamas, Suzanne Pamela, Grandez Castillo, Gustavo Alberto, Lama, Javier R, Matta Aguirre, Milagros Erika, Arancibia Luna, Lesly Angela, Carbajal Paulet, Óscar, Zambrano Ortiz, José, Camara, Anais, Guzman Quintanilla, Fernanda, Diaz-Parra, Carmen, Morales-Oliva, Jose, Cornejo, Rubelio E, Ricalde, Sheby A, Vidal, Jhonny, Rios Nogales, Luis, Cheatham-Seitz, Darline, Gregoraci, Giorgia, Brecx, Alain, Walz, Lisa, Vahrenhorst, Dominik, Seibel, Tobias, Quintini, Gianluca, Kremsner, Peter G, Ahuad Guerrero, Rodolfo Andrés, Arana-Arri, Eunate, Aroca Martinez, Gustavo Jose, Bonten, Marc, Chandler, Reynaldo, Corral, Gonzalo, De Block, Eddie Jan Louis, Ecker, Lucie, Gabor, Julian Justin, Garcia Lopez, Carlos Alberto, Gonzales, Lucy, Granados González, María Angélica, Gorini, Nestor, Grobusch, Martin P, Hrabar, Adrian D, Junker, Helga, Kimura, Alan, Lanata, Claudio F, Lehmann, Clara, Leroux-Roels, Isabel, Mann, Philipp, Martinez-Reséndez, Michel Fernando, Ochoa, Theresa J, Poy, Carlos Alberto, Reyes Fentanes, Maria Jose, Rivera Mejia, Luis Maria, Ruiz Herrera, Vida Veronica, Sáez-Llorens, Xavier, Schönborn-Kellenberger, Oliver, Schunk, Mirjam, Sierra Garcia, Alexandra, Vergara, Itziar, Verstraeten, Thomas, Vico, Marisa, and Oostvogels, Lidia
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- 2022
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5. Safety and Immunogenicity of a DNA Vaccine With Subtype C gp120 Protein Adjuvanted With MF59 or AS01 B : A Phase 1/2a HIV-1 Vaccine Trial.
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Garrett, Nigel, Dintwe, One, Monaco, Cynthia L., Jones, Megan, Seaton, Kelly E., Church, E. Chandler, Grunenberg, Nicole, Hutter, Julia, deCamp, Allan, Huang, Yunda, Lu, Huiyin, Mann, Philipp, Robinson, Samuel T., Heptinstall, Jack, Jensen, Ryan L., Pantaleo, Giuseppe, Ding, Song, Koutsoukos, Marguerite, Hosseinipour, Mina C., and Van Der Meeren, Olivier
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- 2024
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6. Validation of complex radiotherapy techniques using polymer gel dosimetry
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Karger, Christian P, primary, Elter, Alina, additional, Dorsch, Stefan, additional, Mann, Philipp, additional, Pappas, Evangelos, additional, and Oldham, Mark, additional
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- 2024
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7. Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study
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Ake, Julie A., Buchbinder, Susan, Buleza, Karen, Cohen, Kristen W., Crowell, Trevor A., Euler, Zelda, Frank, Ian, Goedhart, Dimitri, Keefer, Michael, Kelly, Colleen, Mayer, Ken, Nkolola, Joseph, Peter, Lauren, Robb, Merlin L., Rouphael, Nadine, Scheppler, Lorenz, Sobieszczyk, Magda, Van Tieu, Hong, Baden, Lindsey R, Stieh, Daniel J, Sarnecki, Michal, Walsh, Stephen R, Tomaras, Georgia D, Kublin, James G, McElrath, M Juliana, Alter, Galit, Ferrari, Guido, Montefiori, David, Mann, Philipp, Nijs, Steven, Callewaert, Katleen, Goepfert, Paul, Edupuganti, Srilatha, Karita, Etienne, Langedijk, Johannes P, Wegmann, Frank, Corey, Lawrence, Pau, Maria G, Barouch, Dan H, Schuitemaker, Hanneke, and Tomaka, Frank
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- 2020
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8. Innate Responses to the Former COVID-19 Vaccine Candidate CVnCoV and Their Relation to Reactogenicity and Adaptive Immunogenicity.
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Wolz, Olaf-Oliver, Vahrenhorst, Dominik, Quintini, Gianluca, Lemberg, Christina, Koch, Sven D., Kays, Sarah-Katharina, Walz, Lisa, Kulkarni, Neeraja, Fehlings, Michael, Wengenmayer, Peter, Heß, Jana, Oostvogels, Lidia, Lazzaro, Sandra, von Eisenhart-Rothe, Philipp, and Mann, Philipp
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IMMUNE response ,COVID-19 pandemic ,VACCINE effectiveness ,COVID-19 vaccines ,HUMORAL immunity - Abstract
Vaccines are highly effective at preventing severe coronavirus disease (COVID-19). With mRNA vaccines, further research is needed to understand the association between immunogenicity and reactogenicity, which is defined as the physical manifestation of an inflammatory response to a vaccination. This study analyzed the immune response and reactogenicity in humans, post immunization, to the former SARS-CoV-2 mRNA investigational vaccine CVnCoV (CV-NCOV-001 and CV-NCOV-002 clinical trials). Immunogenicity was investigated using whole-blood RNA sequencing, serum cytokine levels, and SARS-CoV-2-specific antibodies. The T cell responses in peripheral blood were assessed using intracellular cytokine staining (ICS) and high-dimensional profiling in conjunction with SARS-CoV-2 antigen-specificity testing via mass cytometry. Reactogenicity was graded after participants' first and second doses of CVnCoV using vaccine-related solicited adverse events (AEs). Finally, a Spearman correlation was performed between reactogenicity, humoral immunity, and serum cytokine levels to assess the relationship between reactogenicity and immunogenicity post CVnCoV vaccination. Our findings showed that the gene sets related to innate and inflammatory immune responses were upregulated one day post CVnCoV vaccination, while the gene sets related to adaptive immunity were upregulated predominantly one week after the second dose. The serum levels of IFNα, IFNγ, IP-10, CXCL11, IL-10, and MCP-1 increased transiently, peaking one day post vaccination. CD4
+ T cells were induced in all vaccinated participants and low frequencies of CD8+ T cells were detected by ex vivo ICS. Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity. [ABSTRACT FROM AUTHOR]- Published
- 2024
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9. Corrigendum to “Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: A phase 2 randomized study” [Vaccine: X 11 (2022) 100189]
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Sáez-Llorens, Xavier, primary, Lanata, Claudio, additional, Aranguren, Elaine, additional, Celis, Carlos R., additional, Cornejo, Rubelio, additional, DeAntonio, Rodrigo, additional, Ecker, Lucie, additional, Garrido, Diegi, additional, Gil, Ana I., additional, Gonzales, Marina, additional, Hess-Holtz, Morgan, additional, Leroux-Roels, Geert, additional, Junker, Helga, additional, Kays, Sarah-Katharina, additional, Koch, Sven D., additional, Lazzaro, Sandra, additional, Mann, Philipp, additional, Quintini, Gianluca, additional, Srivastava, Barkha, additional, Vahrenhorst, Dominik, additional, von Eisenhart-Rothe, Philipp, additional, Wolz, Olaf-Oliver, additional, and Oostvogels, Lidia, additional
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- 2023
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10. Safety and Immunogenicity of PENNVAX-G DNA Prime Administered by Biojector 2000 or CELLECTRA Electroporation Device With Modified Vaccinia Ankara-CMDR Boost
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Ake, Julie A., Schuetz, Alexandra, Pegu, Poonam, Wieczorek, Lindsay, Eller, Michael A., Kibuuka, Hannah, Sawe, Fredrick, Maboko, Leonard, Polonis, Victoria, Karasavva, Nicos, Weiner, David, Sekiziyivu, Arthur, Kosgei, Josphat, Missanga, Marco, Kroidl, Arne, Mann, Philipp, Ratto-Kim, Silvia, Eller, Leigh Anne, Earl, Patricia, Moss, Bernard, Dorsey-Spitz, Julie, Milazzo, Mark, Ouedraogo, G. Laissa, Rizvi, Farrukh, Yan, Jian, Khan, Amir S., Peel, Sheila, Sardesai, Niranjan Y., Michael, Nelson L., Ngauy, Viseth, Marovich, Mary, and Robb, Merlin L.
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- 2017
11. High prevalence of ST-elevation, early repolarization, and left ventricular hypertrophy during the eligibility assessment for an HIV vaccine trial in young, healthy Tanzanians
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Mann, Philipp, Munseri, Patricia, Missanga, Marco, Lwakatare, Johnson, Janabi, Mohamed, Kapesa, Emanuel, Robb, Merlin L., Hoelscher, Michael, McCormack, Sheena, Bakari, Muhammad, Maboko, Leonard, Sandström, Eric, and Kroidl, Arne
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- 2017
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12. Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials
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Moodie, Zoe, Walsh, Stephen R., Laher, Fatima, Maganga, Lucas, Herce, Michael E., Naidoo, Sarita, Hosseinipour, Mina C., Innes, Craig, Bekker, Linda-Gail, Grunenberg, Nicole, Mann, Philipp, Yu, Chenchen, deCamp, Allan C., Miner, Maurine D., Yates, Nicole L., Heptinstall, Jack, Mkhize, Nonhlanhla N., Dintwe, One, Frahm, Nicole, Cohen, Kristen W., Allen, Mary, Hutter, Julia, Wagner, Ralf, Pantaleo, Giuseppe, McElrath, M. Juliana, Tomaras, Georgia D., Morris, Lynn, Montefiori, David C., Andersen-Nissen, Erica, Gray, Glenda E., Gilbert, Peter B., and Kublin, James G.
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Clinical trials ,AIDS vaccines ,Genetic research ,HIV antigens ,HIV -- Drug therapy ,DNA ,Vaccination ,T cells ,Biological sciences - Abstract
Background DNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle. Methods and findings The primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%-32.2%, p < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42-3.92, p 98% in both trials, with significantly higher 50% inhibitory dilution (ID.sub.50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67-2.83, p < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48-2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%-56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%-63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%-82.7%, p < 0.001 for Gag LAI/ZM96). The study's main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non-vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects. Conclusions In this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy., Author(s): Zoe Moodie 1,*, Stephen R. Walsh 2,3,4, Fatima Laher 5, Lucas Maganga 6, Michael E. Herce 7, Sarita Naidoo 8, Mina C. Hosseinipour 9, Craig Innes 10, Linda-Gail Bekker [...]
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- 2020
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13. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial
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Kremsner, Peter G., Ahuad Guerrero, Rodolfo Andres, Arana-Arri, Eunate, Aroca Martinez, Gustavo Jose, Bonten, Marc, Chandler, Reynaldo, Corral, Gonzalo, Louis De Block, Eddie Jan, Ecker, Lucie, Justin Gabor, Julian, Garcia Lopez, Carlos Alberto, Gonzales, Lucy, Granados Gonzalez, Maria Angelica, Gorini, Nestor, Grobusch, Martin P., Hrabar, Adrian D., Junker, Helga, Kimura, Alan, Lanata, Claudio F., Lehmann, Clara, Leroux-Roels, Isabel, Mann, Philipp, Fernando Martinez-Resendez, Michel, Ochoa, Theresa J., Alberto Poy, Carlos, Reyes Fentanes, Maria Jose, Rivera Mejia, Luis Maria, Ruiz Herrera, Vida Veronica, Saez-Llorens, Xavier, Schoenborn-Kellenberger, Oliver, Schunk, Mirjam, Sierra Garcia, Alexandra, Vergara, Itziar, Verstraeten, Thomas, Vico, Marisa, Oostvogels, Lidia, Kremsner, Peter G., Ahuad Guerrero, Rodolfo Andres, Arana-Arri, Eunate, Aroca Martinez, Gustavo Jose, Bonten, Marc, Chandler, Reynaldo, Corral, Gonzalo, Louis De Block, Eddie Jan, Ecker, Lucie, Justin Gabor, Julian, Garcia Lopez, Carlos Alberto, Gonzales, Lucy, Granados Gonzalez, Maria Angelica, Gorini, Nestor, Grobusch, Martin P., Hrabar, Adrian D., Junker, Helga, Kimura, Alan, Lanata, Claudio F., Lehmann, Clara, Leroux-Roels, Isabel, Mann, Philipp, Fernando Martinez-Resendez, Michel, Ochoa, Theresa J., Alberto Poy, Carlos, Reyes Fentanes, Maria Jose, Rivera Mejia, Luis Maria, Ruiz Herrera, Vida Veronica, Saez-Llorens, Xavier, Schoenborn-Kellenberger, Oliver, Schunk, Mirjam, Sierra Garcia, Alexandra, Vergara, Itziar, Verstraeten, Thomas, Vico, Marisa, and Oostvogels, Lidia
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Background Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. Methods HERALD is a randomised, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America. By use of an interactive web response system and stratification by country and age group (18-60 years and >= 61 years), adults with no history of virologically confirmed COVID-19 were randomly assigned (1:1) to receive intramuscularly either two 0.6 mL doses of CVnCoV containing 12 mu g of mRNA or two 0.6 mL doses of 0.9% NaCl (placebo) on days 1 and 29. The primary efficacy endpoint was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose. For the primary endpoint, the trial was considered successful if the lower limit of the CI was greater than 30%. Key secondary endpoints were the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, severe COVID-19, and COVID-19 of any severity by age group. Primary safety outcomes were solicited local and systemic adverse events within 7 days after each dose and unsolicited adverse events within 28 days after each dose in phase 2b participants, and serious adverse events and adverse events of special interest up to 1 year after the second dose in phase 2b and phase 3 participants. Here, we report data up to June 18, 2021. The study is registered at ClinicalTrials.gov, NCT04652102, and EudraCT, 2020-003998-22, and is ongoing. Findings Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48.2 days (SE 0.2), 83
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- 2022
14. Safety and Immunogenicity of Ad26-vectored HIV Vaccine with Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-uninfected Adults: A Phase 1/2a Study.
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Stieh, Daniel J, Barouch, Dan H, Comeaux, Christy, Sarnecki, Michal, Stephenson, Kathryn E, Walsh, Stephen R, Sawant, Sheetal, Heptinstall, Jack, Tomaras, Georgia D, Kublin, James G, McElrath, M Juliana, Cohen, Kristen W, Rosa, Stephen C De, Alter, Galit, Ferrari, Guido, Montefiori, David, Mann, Philipp, Nijs, Steven, Callewaert, Katleen, and Goepfert, Paul A
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AIDS vaccines ,IMMUNE response ,C++ ,CLINICAL trial registries ,HIV infections - Abstract
Background: Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV.Methods: This placebo-controlled, double-blind, phase 1/2a study (NCT02935686) enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and Pol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), bivalent protein regimen (clade C regimen plus mosaic gp140), or placebo. Primary endpoints were safety and antibody responses.Results: 152/155 participants (clade C [n = 26], bivalent protein [n = 103], placebo [n = 26]) received ≥1 injection. The highest adverse event (AE) severity was grade 3 (local pain/tenderness: 12%, 2%, and 0% of the respective groups; solicited systemic AEs: 19%, 15%, 0%). HIV-1 mosaic gp140-binding antibody titers were 79,595 ELISA units [EU]/mL and 137,520 EU/mL in the clade C and bivalent protein groups (P < .001) post-dose 4 and 16,862 EU/mL and 25,162 EU/mL 6 months later. Antibody response breadth against clade C gp140 and clade C/non-clade C gp120 was highest in the bivalent protein group.Conclusions: Adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without compromising safety or clade C responses. [ABSTRACT FROM AUTHOR]- Published
- 2023
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15. A Third Dose of the COVID-19 Vaccine, CVnCoV, Increased the Neutralizing Activity against the SARS-CoV-2 Wild-Type and Delta Variant
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Wolz, Olaf-Oliver, primary, Kays, Sarah-Katharina, additional, Junker, Helga, additional, Koch, Sven D., additional, Mann, Philipp, additional, Quintini, Gianluca, additional, von Eisenhart-Rothe, Philipp, additional, and Oostvogels, Lidia, additional
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- 2022
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16. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial
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Kremsner, Peter G, primary, Ahuad Guerrero, Rodolfo Andrés, additional, Arana-Arri, Eunate, additional, Aroca Martinez, Gustavo Jose, additional, Bonten, Marc, additional, Chandler, Reynaldo, additional, Corral, Gonzalo, additional, De Block, Eddie Jan Louis, additional, Ecker, Lucie, additional, Gabor, Julian Justin, additional, Garcia Lopez, Carlos Alberto, additional, Gonzales, Lucy, additional, Granados González, María Angélica, additional, Gorini, Nestor, additional, Grobusch, Martin P, additional, Hrabar, Adrian D, additional, Junker, Helga, additional, Kimura, Alan, additional, Lanata, Claudio F, additional, Lehmann, Clara, additional, Leroux-Roels, Isabel, additional, Mann, Philipp, additional, Martinez-Reséndez, Michel Fernando, additional, Ochoa, Theresa J, additional, Poy, Carlos Alberto, additional, Reyes Fentanes, Maria Jose, additional, Rivera Mejia, Luis Maria, additional, Ruiz Herrera, Vida Veronica, additional, Sáez-Llorens, Xavier, additional, Schönborn-Kellenberger, Oliver, additional, Schunk, Mirjam, additional, Sierra Garcia, Alexandra, additional, Vergara, Itziar, additional, Verstraeten, Thomas, additional, Vico, Marisa, additional, Oostvogels, Lidia, additional, Lovesio, Luciano, additional, Diez, Fabián, additional, Grazziani, Franco, additional, Ganaha, Maria Cristina, additional, Zalatnik, Viviana Judith, additional, Dittrich, Ricardo Julio, additional, Espínola, Lidia, additional, Lambert, Sandra, additional, Longhi, Andrea, additional, Vecchio, Claudia, additional, Mastruzzo, María, additional, Fernandez, Alberto, additional, Borchowiek, Silvina, additional, Potito, Roberto, additional, Ahuad Guerrero, Rodolfo Andres, additional, Guardiani, Fernando Martin, additional, Castella, Sofia, additional, Foccoli, Monica, additional, Pedernera, Aldana, additional, Braida, Ariel, additional, Durigan, Virginia, additional, Martella, Carolina, additional, Bobat, Antonela, additional, Boggia, Bruno Emilio, additional, Nemi, Sergio Andrés, additional, Tartaglione, Javier Gerardo, additional, Piedimonte, Fabián César, additional, De Bie, Jessie, additional, Reynales Londoño, Humberto, additional, Rodríguez Ordoñez, Paula Andrea, additional, García Cruz, Johanna Marcela, additional, Bautista Toloza, Leonardo, additional, Ladino González, Margot Cecilia, additional, Zambrano Ochoa, Adriana Pilar, additional, Prieto Pradera, Iñigo, additional, Torres Hernandez, Daniela, additional, Mazo Elorza, Diana Patricia, additional, Collazos Lennis, Maria Fernanda, additional, Vanegas Dominguez, Beatriz, additional, Solano Mosquera, Lina Marianur, additional, Fendel, Rolf, additional, Fleischmann, Wim Alexander, additional, Koehne, Erik, additional, Kreidenweiss, Andrea, additional, Köhler, Carsten, additional, Esen, Meral, additional, Horn, Carola, additional, Eberts, Sandra, additional, Kroidl, Arne, additional, Huber, Kristina, additional, Thiel, Verena, additional, Mazara Rosario, Sonia, additional, Reyes, Gilda, additional, Rivera, Laura, additional, Donastorg, Yeycy, additional, Lantigua, Flavia, additional, Torres Almanzar, Dania, additional, Candelario, Rosalba, additional, Peña Mendez, Lourdes, additional, Rosario Gomez, Nadia, additional, Portolés-Pérez, Antonio, additional, Ascaso del Río, Ana, additional, Laredo Velasco, Leonor, additional, Bustinduy Odriozola, Maria Jesus, additional, Larrea Arranz, Igor, additional, Martínez Alcorta, Luis Ignacio, additional, Durán Laviña, María Isabel, additional, Imaz-Ayo, Natale, additional, Meijide, Susana, additional, García-de-Vicuña, Aitor, additional, Santorcuato, Ana, additional, Gallego, Mikel, additional, Aguirre-García, Gloria Mayela, additional, Olmos Vega, Jocelyn, additional, González Limón, Pablo, additional, Vázquez Villar, Andrea, additional, Chávez Barón, Jaime, additional, Arredondo Saldaña, Felipe, additional, Luján Palacios, Juan de Dios, additional, Camacho Choza, Laura Julia, additional, Vázquez Saldaña, Eduardo Gabriel, additional, Ortega Dominguez, Sandra Janeth, additional, Vega Orozco, Karen Sofia, additional, Torres Quiroz, Ivonne Aimee, additional, Martinez Avendaño, Alejandro, additional, Herrera Sanchez, Javier, additional, Guzman, Esperanza, additional, Castro Castrezana, Laura, additional, Ruiz Palacios y Santos, Guillermo Miguel, additional, de Winter, Ronald Frank Jacobus, additional, de Jonge, Hanna K, additional, Schnyder, Jenny L, additional, Boersma, Wim, additional, Hessels, Lisa, additional, Djamin, Remco, additional, van der Sar, Simone, additional, DeAntonio, Rodrigo, additional, Peña, Moisés, additional, Rebollon, Gabriel, additional, Rojas, Marianela, additional, Escobar, Johnny, additional, Hammerschlag Icaza, Bruno, additional, Wong T, Digna Y, additional, Barrera Perigault, Paulo, additional, Ruiz, Sergio, additional, Chan, Milagros, additional, Arias Hoo, Dommie Janneth, additional, Gil, Ana I, additional, Celis, Carlos R, additional, Balmaceda, Maria Pia, additional, Flores, Omar, additional, Ochoa, Mayra, additional, Peña, Bia, additional, de la Flor, Carolina, additional, Webb, Camille María, additional, Cornejo, Enrique, additional, Sanes, Fatima, additional, Mayorga, Valerie, additional, Valdiviezo, Gladys, additional, Ramírez Lamas, Suzanne Pamela, additional, Grandez Castillo, Gustavo Alberto, additional, Lama, Javier R, additional, Matta Aguirre, Milagros Erika, additional, Arancibia Luna, Lesly Angela, additional, Carbajal Paulet, Óscar, additional, Zambrano Ortiz, José, additional, Camara, Anais, additional, Guzman Quintanilla, Fernanda, additional, Diaz-Parra, Carmen, additional, Morales-Oliva, Jose, additional, Cornejo, Rubelio E, additional, Ricalde, Sheby A, additional, Vidal, Jhonny, additional, Rios Nogales, Luis, additional, Cheatham-Seitz, Darline, additional, Gregoraci, Giorgia, additional, Brecx, Alain, additional, Walz, Lisa, additional, Vahrenhorst, Dominik, additional, Seibel, Tobias, additional, and Quintini, Gianluca, additional
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- 2022
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17. Third dose of COVID-19 vaccine, CVnCoV, increased neutralizing activity against SARS-CoV-2 wild-type and Delta variant
- Author
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Wolz, Olaf-Oliver, primary, Kays, Sarah-Katharina, additional, Junker, Helga, additional, Koch, Sven Dominik, additional, Mann, Philipp, additional, Quintini, Gianluca, additional, von Eisenhart-Rothe, Philipp, additional, and Oostvogels, Lidia, additional
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- 2022
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18. Technical Note: On the feasibility of performing dosimetry in target and organ at risk using polymer dosimetry gel and thermoluminescence detectors in an anthropomorphic, deformable, and multimodal pelvis phantom
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Marot, Mathieu, primary, Elter, Alina, additional, Mann, Philipp, additional, Schwahofer, Andrea, additional, Lang, Clemens, additional, Johnen, Wibke, additional, Körber, Stefan A., additional, Beuthien‐Baumann, Bettina, additional, and Gillmann, Clarissa, additional
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- 2021
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19. Strong Spin-Orbit Torque effect on magnetic defects due to topological surface state electrons in Bi$_{2}$Te$_{3}$
- Author
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Kosma, Adamantia, R����mann, Philipp, Bl��gel, Stefan, and Mavropoulos, Phivos
- Subjects
Condensed Matter - Materials Science ,Condensed Matter - Mesoscale and Nanoscale Physics ,Mesoscale and Nanoscale Physics (cond-mat.mes-hall) ,Materials Science (cond-mat.mtrl-sci) ,FOS: Physical sciences ,Condensed Matter::Strongly Correlated Electrons - Abstract
We investigate the spin-orbit torque exerted on the magnetic moments of the transition-metal impurities Cr, Mn, Fe and Co, embedded in the surface of the topological insulator Bi$_{2}$Te$ _{3} $, in response to an electric field and a consequent electrical current flow in the surface. The multiple scattering problem of electrons off impurity atoms is solved by first-principles calculations within the full-potential relativistic Korringa-Kohn-Rostoker (KKR) Green function method, while the spin-orbit torque calculations are carried out by combining the KKR method with the semiclassical Boltzmann transport equation. We analyze the correlation of the spin-orbit torque to the spin accumulation and spin flux in the defects. We compare the torque on different magnetic impurities and unveil the effect of resonant scattering. In addition, we calculate the resistivity and the Joule heat as a function of the torque in these systems. We predict that the Mn/Bi$_{2}$Te$_{3}$ is optimal among the studied systems.
- Published
- 2020
20. mdbrain vs. FreeSurfer: Repeatability and performance measurements in brain volumetry
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Mann, Philipp
- Subjects
Not applicable ,Computer Applications-Detection, diagnosis ,Neuroradiology brain ,Artificial Intelligence ,Artificial Intelligence and Machine Learning ,Dementia ,Computer applications ,MR ,Neural networks - Abstract
Purpose Methods and materials Results Conclusion Personal information and conflict of interest References, Purpose: Quantitative brain analysis is becoming more and more important. Although there are algorithms that are used as academic standards, applications in the clinic is not easy (long computation time, weak workflow integration, no FDA/CE clearance). This...
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- 2020
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21. Efficacy and Safety of the CVnCoV SARS-CoV-2 mRNA Vaccine Candidate: Results from Herald, a Phase 2b/3, Randomised, Observer-Blinded, Placebo-Controlled Clinical Trial in Ten Countries in Europe and Latin America
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Kremsner, Peter G., primary, Guerrero, Rodolfo Andrés Ahuad, additional, Arana, Eunate, additional, Aroca Martinez, Gustavo Jose, additional, Bonten, Marc J.M., additional, Chandler, Reynaldo, additional, Corral, Gonzalo, additional, De Block, Eddie Jan Louis, additional, Ecker, Lucie, additional, Gabor, Julian Justin, additional, Garcia Lopez, Carlos Alberto, additional, Gonzales, Lucy, additional, Granados González, María Angélica, additional, Gorini, Nestor, additional, Grobusch, Martin P., additional, Hrabar, Adrian D., additional, Junker, Helga, additional, Kimura, Alan, additional, Lanata, Claudio F., additional, Lehmann, Clara, additional, Leroux-Roels, Isabel, additional, Mann, Philipp, additional, Martinez-Reséndez, Michel Fernando, additional, Ochoa, Theresa, additional, Poy, Carlos Alberto, additional, Reyes Fentanes, Maria Jose, additional, Mejia, Luis Maria Rivera, additional, Ruiz Herrera, Vida Veronica, additional, Sáez-Llorens, Xavier, additional, Schönborn-Kellenberger, Oliver, additional, Schunk, Mirjam, additional, Garcia, Alexandra Sierra, additional, Vergara, Itziar, additional, Verstraeten, Thomas, additional, Vico, Marisa, additional, Oostvogels, Lidia, additional, and Group, HERALD Study, additional
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- 2021
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22. Safety and Immunogenicity of mRNA-LNP COVID-19 Vaccine CVnCoV in Latin American Adults; A Phase 2 Randomized Study
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Sáez-Llorens, Xavier, primary, Lanata, Claudio F., additional, Aranguren, Elaine, additional, Celis, Carlos R., additional, Cornejo, Rubelio, additional, DeAntonio, Rodrigo, additional, Ecker, Lucie, additional, Garrido, Diegi, additional, Gil, Ana I., additional, Gonzales, Marina, additional, Hess-Holtz, Morgan, additional, Leroux-Roels, Geert, additional, Junker, Helga, additional, Kays, Sarah-Katharina, additional, Koch, Sven D., additional, Lazzaro, Sandra, additional, Mann, Philipp, additional, Quintini, Gianluca, additional, Srivastava, Barkha, additional, Vahrenhorst, Dominik, additional, von Eisenhart-Rothe, Philipp, additional, Wolz, Olaf-Oliver, additional, and Oostvogels, Lidia, additional
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- 2021
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23. Technical Note: ADAM PETer – An anthropomorphic, deformable and multimodality pelvis phantom with positron emission tomography extension for radiotherapy
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Gillmann, Clarissa, primary, Homolka, Noa, additional, Johnen, Wibke, additional, Runz, Armin, additional, Echner, Gernot, additional, Pfaffenberger, Asja, additional, Mann, Philipp, additional, Schneider, Verena, additional, Hoffmann, Aswin L., additional, Troost, Esther G. C., additional, Koerber, Stefan A., additional, Kotzerke, Jörg, additional, and Beuthien‐Baumann, Bettina, additional
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- 2020
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24. Phase 1 Assessment of the Safety and Immunogenicity of an mRNA- Lipid Nanoparticle Vaccine Candidate Against SARS-CoV-2 in Human Volunteers
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Kremsner, Peter, primary, Mann, Philipp, additional, Bosch, Jacobus, additional, Fendel, Rolf, additional, Gabor, Julian J., additional, Kreidenweiss, Andrea, additional, Kroidl, Arne, additional, Leroux-Roels, Isabel, additional, Leroux-Roels, Geert, additional, Schindler, Christoph, additional, Schunk, Mirjam, additional, Velavan, Thirumalaisamy P., additional, Fotin-Mleczek, Mariola, additional, Müller, Stefan, additional, Quintini, Gianluca, additional, Schönborn-Kellenberger, Oliver, additional, Vahrenhorst, Dominik, additional, Verstraeten, Thomas, additional, Walz, Lisa, additional, Wolz, Olaf-Oliver, additional, and Oostvogels, Lidia, additional
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- 2020
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25. Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study
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Baden, Lindsey R, primary, Stieh, Daniel J, additional, Sarnecki, Michal, additional, Walsh, Stephen R, additional, Tomaras, Georgia D, additional, Kublin, James G, additional, McElrath, M Juliana, additional, Alter, Galit, additional, Ferrari, Guido, additional, Montefiori, David, additional, Mann, Philipp, additional, Nijs, Steven, additional, Callewaert, Katleen, additional, Goepfert, Paul, additional, Edupuganti, Srilatha, additional, Karita, Etienne, additional, Langedijk, Johannes P, additional, Wegmann, Frank, additional, Corey, Lawrence, additional, Pau, Maria G, additional, Barouch, Dan H, additional, Schuitemaker, Hanneke, additional, Tomaka, Frank, additional, Ake, Julie A., additional, Buchbinder, Susan, additional, Buleza, Karen, additional, Cohen, Kristen W., additional, Crowell, Trevor A., additional, Euler, Zelda, additional, Frank, Ian, additional, Goedhart, Dimitri, additional, Keefer, Michael, additional, Kelly, Colleen, additional, Mayer, Ken, additional, Nkolola, Joseph, additional, Peter, Lauren, additional, Robb, Merlin L., additional, Rouphael, Nadine, additional, Scheppler, Lorenz, additional, Sobieszczyk, Magda, additional, and Van Tieu, Hong, additional
- Published
- 2020
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26. Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2: A phase 1 randomized clinical trial.
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Kremsner, Peter G., Mann, Philipp, Kroidl, Arne, Leroux-Roels, Isabel, Schindler, Christoph, Gabor, Julian J., Schunk, Mirjam, Leroux-Roels, Geert, Bosch, Jacobus J., Fendel, Rolf, Kreidenweiss, Andrea, Velavan, Thirumalaisamy P., Fotin-Mleczek, Mariola, Mueller, Stefan O., Quintini, Gianluca, Schönborn‑Kellenberger, Oliver, Vahrenhorst, Dominik, Verstraeten, Thomas, Alves de Mesquita, Margarida, and Walz, Lisa
- Abstract
Summary: Background: We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods: This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN
50 ). Results: In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion: In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera. [ABSTRACT FROM AUTHOR]- Published
- 2021
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27. Technical Note: ADAM PETer – An anthropomorphic, deformable and multimodality pelvis phantom with positron emission tomography extension for radiotherapy.
- Author
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Gillmann, Clarissa, Homolka, Noa, Johnen, Wibke, Runz, Armin, Echner, Gernot, Pfaffenberger, Asja, Mann, Philipp, Schneider, Verena, Hoffmann, Aswin L., Troost, Esther G. C., Koerber, Stefan A., Kotzerke, Jörg, and Beuthien‐Baumann, Bettina
- Subjects
POSITRON emission tomography ,MAGNETIC resonance imaging ,PELVIS ,COMPUTED tomography ,PELVIC bones ,LYMPHATIC metastasis - Abstract
Objective: To develop an anthropomorphic, deformable and multimodal pelvis phantom with positron emission tomography extension for radiotherapy (ADAM PETer). Methods: The design of ADAM PETer was based on our previous pelvis phantom (ADAM) and extended for compatibility with PET and use in 3T magnetic resonance imaging (MRI). The formerly manually manufactured silicon organ surrogates were replaced by three‐dimensional (3D) printed organ shells. Two intraprostatic lesions, four iliac lymph node metastases and two pelvic bone metastases were added to simulate prostate cancer as multifocal and metastatic disease. Radiological properties [computed tomography (CT) and 3T MRI] of cortical bone, bone marrow and adipose tissue were simulated by heavy gypsum, a mixture of Vaseline and K2HPO4 and peanut oil, respectively. For soft tissues, agarose gels with varying concentrations of agarose, gadolinium (Gd) and sodium fluoride (NaF) were developed. The agarose gels were doped with patient‐specific activity concentrations of a Fluorine‐18 labelled compound and then filled into the 3D printed organ shells of prostate lesions, lymph node and bone metastases. The phantom was imaged at a dual energy CT and a 3T PET/MRI scanner. Results: The compositions of the soft tissue surrogates are the following (given as mass fractions of agarose[w%]/NaF[w%]/Gd[w%]): Muscle (4/1/0.027), prostate (1.35/4.2/0.011), prostate lesions (2.25/4.2/0.0085), lymph node and bone metastases (1.4/4.2/0.025). In all imaging modalities, the phantom simulates human contrast. Intraprostatic lesions appear hypointense as compared to the surrounding normal prostate tissue in T2‐weighted MRI. The PET signal of all tumors can be localized as focal spots at their respective site. Activity concentrations of 12.0 kBq/mL (prostate lesion), 12.4 kBq/mL (lymph nodes) and 39.5 kBq/mL (bone metastases) were measured. Conclusion: The ADAM PETer pelvis phantom can be used as multimodal, anthropomorphic model for CT, 3T‐MRI and PET measurements. It will be central to simulate and optimize the technical workflow for the integration of PET/MRI‐based radiation treatment planning of prostate cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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28. Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein.
- Author
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Hosseinipour, Mina C, Innes, Craig, Naidoo, Sarita, Mann, Philipp, Hutter, Julia, Ramjee, Gita, Sebe, Modulakgotla, Maganga, Lucas, Herce, Michael E, deCamp, Allan C, Marshall, Kyle, Dintwe, One, Andersen-Nissen, Erica, Tomaras, Georgia D, Mkhize, Nonhlanhla, Morris, Lynn, Jensen, Ryan, Miner, Maurine D, Pantaleo, Giuseppe, and Ding, Song
- Subjects
DNA ,HIV ,IMMUNIZATION ,STATISTICAL sampling ,RANDOMIZED controlled trials - Abstract
Background The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. Methods In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1–uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. Results All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4
+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P =.02), but not in the coadministration regimen (43.3% vs 48.3%; P =.61). Conclusions Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. Clinical Trials Registration South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27–0715–4917) and ClinicalTrials.gov (NCT02997969). [ABSTRACT FROM AUTHOR]- Published
- 2021
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29. Development and implementation of 3D-dosimetric end-to-end tests in adaptive radiation therapy of moving tumors
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Mann, Philipp
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530 Physics ,600 Technology (Applied sciences) - Abstract
Clinical implementation of novel advanced treatment techniques in adaptive radiation therapy requires proper workflow verification. However, this subject is not satisfactorily solved yet as current experimental validation techniques do not reflect the complexity of real patient treatments. In this thesis, several methods for patient-specific end-to-end tests were developed and applied to clinical workflows especially including treatments of moving tumors. End-to-end-tests were performed with geometrically well-defined phantoms as well as with an anthropomorphic dynamic ex-vivo porcine lung phantom in combination with a 3-dimensional (3D) polymer gel dosimeter (PGD). Different experimental settings of increasing complexity were tested in terms of (i) accuracy, (ii) feasibility of clinical workflows testing, (iii) validation of clinical concepts for motion-compensated treatments, (iv) additional integration of real-time markerless fluoroscopic imaging, and (v) validation of 4D dose calculation algorithms. Phantom irradiations were performed under static and dynamic conditions with and without beam gating. PGD evaluation revealed good tumor coverage for all treatment concepts and beam gating significantly reduced normal tissue exposure. In all cases, good agreement with the calculated dose distribution was obtained. As a conclusion, the established experimental workflow provides a versatile and valuable tool for geometrical and dosimetrical validation of advanced motion-compensated treatment techniques in adaptive radiation therapy.
- Published
- 2017
30. A peripheral epigenetic signature of immune system genes is linked to neocortical thickness and memory
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Freytag, Virginie, Carrillo-Roa, Tania, Milnik, Annette, Mann, Philipp G. Sa, Vukojevic, Vanja, Coynel, David, Demougin, Philippe, Egli, Tobias, Gschwind, Leo, Jessen, Frank, Loos, Eva, Maier, Wolfgang, Riedel-Heller, Steffi G., Scherer, Martin, Vogler, Christian, Wagner, Michael, Binder, Elisabeth B., de Quervain, Dominique J. -F., Papassotiropoulos, Andreas, Freytag, Virginie, Carrillo-Roa, Tania, Milnik, Annette, Mann, Philipp G. Sa, Vukojevic, Vanja, Coynel, David, Demougin, Philippe, Egli, Tobias, Gschwind, Leo, Jessen, Frank, Loos, Eva, Maier, Wolfgang, Riedel-Heller, Steffi G., Scherer, Martin, Vogler, Christian, Wagner, Michael, Binder, Elisabeth B., de Quervain, Dominique J. -F., and Papassotiropoulos, Andreas
- Abstract
Increasing age is tightly linked to decreased thickness of the human neocortex. The biological mechanisms that mediate this effect are hitherto unknown. The DNA methylome, as part of the epigenome, contributes significantly to age-related phenotypic changes. Here, we identify an epigenetic signature that is associated with cortical thickness (P = 3.86 x 10(-8)) and memory performance in 533 healthy young adults. The epigenetic effect on cortical thickness was replicated in a sample comprising 596 participants with major depressive disorder and healthy controls. The epigenetic signature mediates partially the effect of age on cortical thickness (P < 0.001). A multilocus genetic score reflecting genetic variability of this signature is associated with memory performance (P = 0.0003) in 3,346 young and elderly healthy adults. The genomic location of the contributing methylation sites points to the involvement of specific immune system genes. The decomposition of blood methylome-wide patterns bears considerable potential for the study of brain-related traits.
- Published
- 2017
31. Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA Prime-Modified Vaccinia Virus Ankara Boost HIV-1 Vaccine Regimen
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Bauer, Asli, primary, Podola, Lilli, additional, Mann, Philipp, additional, Missanga, Marco, additional, Haule, Antelmo, additional, Sudi, Lwitiho, additional, Nilsson, Charlotta, additional, Kaluwa, Bahati, additional, Lueer, Cornelia, additional, Mwakatima, Maria, additional, Munseri, Patricia J., additional, Maboko, Leonard, additional, Robb, Merlin L., additional, Tovanabutra, Sodsai, additional, Kijak, Gustavo, additional, Marovich, Mary, additional, McCormack, Sheena, additional, Joseph, Sarah, additional, Lyamuya, Eligius, additional, Wahren, Britta, additional, Sandström, Eric, additional, Biberfeld, Gunnel, additional, Hoelscher, Michael, additional, Bakari, Muhammad, additional, Kroidl, Arne, additional, and Geldmacher, Christof, additional
- Published
- 2017
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32. Investigation of the halo-artifact in 68Ga-PSMA-11-PET/MRI
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Heußer, Thorsten, primary, Mann, Philipp, additional, Rank, Christopher M., additional, Schäfer, Martin, additional, Dimitrakopoulou-Strauss, Antonia, additional, Schlemmer, Heinz-Peter, additional, Hadaschik, Boris A., additional, Kopka, Klaus, additional, Bachert, Peter, additional, Kachelrieß, Marc, additional, and Freitag, Martin T., additional
- Published
- 2017
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33. Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design.
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Viegas, Edna O., Kroidl, Arne, Munseri, Patricia J., Missanga, Marco, Nilsson, Charlotta, Tembe, Nelson, Bauer, Asli, Joachim, Agricola, Joseph, Sarah, Mann, Philipp, Geldmacher, Christof, Fleck, Sue, Stöhr, Wolfgang, Scarlatti, Gabriella, Aboud, Said, Bakari, Muhammad, Maboko, Leonard, Hoelscher, Michael, Wahren, Britta, and Robb, Merlin L.
- Subjects
INTRADERMAL injections ,HIV virus evolution ,IMMUNOGENETICS ,ELECTROPORATION ,BIOELECTROCHEMISTRY - Abstract
Background: We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. Methods: Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 10
8 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. Results: Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost. Conclusion: Intradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses. [ABSTRACT FROM AUTHOR]- Published
- 2018
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34. Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial
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Joachim, Agricola, primary, Bauer, Asli, additional, Joseph, Sarah, additional, Geldmacher, Christof, additional, Munseri, Patricia J., additional, Aboud, Said, additional, Missanga, Marco, additional, Mann, Philipp, additional, Wahren, Britta, additional, Ferrari, Guido, additional, Polonis, Victoria R., additional, Robb, Merlin L., additional, Weber, Jonathan, additional, Tatoud, Roger, additional, Maboko, Leonard, additional, Hoelscher, Michael, additional, Lyamuya, Eligius F., additional, Biberfeld, Gunnel, additional, Sandström, Eric, additional, Kroidl, Arne, additional, Bakari, Muhammad, additional, Nilsson, Charlotta, additional, and McCormack, Sheena, additional
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- 2016
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35. Technical Note: Radiological properties of tissue surrogates used in a multimodality deformable pelvic phantom for MR‐guided radiotherapy
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Niebuhr, Nina I., primary, Johnen, Wibke, additional, Güldaglar, Timur, additional, Runz, Armin, additional, Echner, Gernot, additional, Mann, Philipp, additional, Möhler, Christian, additional, Pfaffenberger, Asja, additional, Jäkel, Oliver, additional, and Greilich, Steffen, additional
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- 2016
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36. AI-based identification of FGFR3 mutation status from routine histology slides of muscle-invasive bladder cancer.
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Saillard, Charlie, Bannier, Pierre-Antoine, Mann, Philipp, Maussion, Charles, Matek, Christian, Hartmann, Arndt, and Eckstein, Markus
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- 2023
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37. Priming with a Simplified Intradermal HIV-1 DNA Vaccine Regimen followed by Boosting with Recombinant HIV-1 MVA Vaccine Is Safe and Immunogenic: A Phase IIa Randomized Clinical Trial
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Munseri, Patricia. J., primary, Kroidl, Arne, additional, Nilsson, Charlotta, additional, Joachim, Agricola, additional, Geldmacher, Christof, additional, Mann, Philipp, additional, Moshiro, Candida, additional, Aboud, Said, additional, Lyamuya, Eligius, additional, Maboko, Leonard, additional, Missanga, Marco, additional, Kaluwa, Bahati, additional, Mfinanga, Sayoki, additional, Podola, Lilly, additional, Bauer, Asli, additional, Godoy-Ramirez, Karina, additional, Marovich, Mary, additional, Moss, Bernard, additional, Hoelscher, Michael, additional, Gotch, Frances, additional, Stöhr, Wolfgang, additional, Stout, Richard, additional, McCormack, Sheena, additional, Wahren, Britta, additional, Mhalu, Fred, additional, Robb, Merlin L., additional, Biberfeld, Gunnel, additional, Sandström, Eric, additional, and Bakari, Muhammad, additional
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- 2015
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38. Investigation of the halo-artifact in 68Ga-PSMA-11-PET/MRI.
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Heußer, Thorsten, Mann, Philipp, Rank, Christopher M., Schäfer, Martin, Dimitrakopoulou-Strauss, Antonia, Schlemmer, Heinz-Peter, Hadaschik, Boris A., Kopka, Klaus, Bachert, Peter, Kachelrieß, Marc, and Freitag, Martin T.
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- *
DIAGNOSIS , *PROSTATE cancer , *PROSTATE-specific membrane antigen , *POSITRON emission tomography , *IMAGING phantoms , *BRAIN imaging - Abstract
Objectives: Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting the prostate-specific membrane antigen (PSMA) with a 68Ga-labelled PSMA-analog (68Ga-PSMA-11) is discussed as a promising diagnostic method for patients with suspicion or history of prostate cancer. One potential drawback of this method are severe photopenic (halo-) artifacts surrounding the bladder and the kidneys in the scatter-corrected PET images, which have been reported to occur frequently in clinical practice. The goal of this work was to investigate the occurrence and impact of these artifacts and, secondly, to evaluate variants of the standard scatter correction method with regard to halo-artifact suppression. Methods: Experiments using a dedicated pelvis phantom were conducted to investigate whether the halo-artifact is modality-, tracer-, and/or concentration-dependent. Furthermore, 31 patients with history of prostate cancer were selected from an ongoing 68Ga-PSMA-11-PET/MRI study. For each patient, PET raw data were reconstructed employing six different variants of PET scatter correction: absolute scatter scaling, relative scatter scaling, and relative scatter scaling combined with prompt gamma correction, each of which was combined with a maximum scatter fraction (MaxSF) of MaxSF = 75% or MaxSF = 40%. Evaluation of the reconstructed images with regard to halo-artifact suppression was performed both quantitatively using statistical analysis and qualitatively by two independent readers. Results: The phantom experiments did not reveal any modality-dependency (PET/MRI vs. PET/CT) or tracer-dependency (68Ga vs. 18F-FDG). Patient- and phantom-based data indicated that halo-artifacts derive from high organ-to-background activity ratios (OBR) between bladder/kidneys and surrounding soft tissue, with a positive correlation between OBR and halo size. Comparing different variants of scatter correction, reducing the maximum scatter fraction from the default value MaxSF = 75% to MaxSF = 40% was found to efficiently suppress halo-artifacts in both phantom and patient data. In 1 of 31 patients, reducing the maximum scatter fraction provided new PET-based information changing the patient’s diagnosis. Conclusion: Halo-artifacts are particularly observed for 68Ga-PSMA-11-PET/MRI due to 1) the biodistribution of the PSMA-11-tracer resulting in large OBRs for bladder and kidneys and 2) inaccurate scatter correction methods currently used in clinical routine, which tend to overestimate the scatter contribution. If not compensated for, 68Ga-PSMA-11 uptake pathologies may be masked by halo-artifacts leading to false-negative diagnoses. Reducing the maximum scatter fraction was found to efficiently suppress halo-artifacts. [ABSTRACT FROM AUTHOR]
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- 2017
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39. Mice Lacking the Nuclear Pore Complex Protein ALADIN Show Female Infertility but Fail To Develop a Phenotype Resembling Human Triple A Syndrome
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Huebner, Angela, primary, Mann, Philipp, additional, Rohde, Elvira, additional, Kaindl, Angela M., additional, Witt, Martin, additional, Verkade, Paul, additional, Jakubiczka, Sibylle, additional, Menschikowski, Mario, additional, Stoltenburg-Didinger, Gisela, additional, and Koehler, Katrin, additional
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- 2006
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40. Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial.
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Gray, Glenda E, Mngadi, Kathryn, Lavreys, Ludo, Nijs, Steven, Gilbert, Peter B, Hural, John, Hyrien, Ollivier, Juraska, Michal, Luedtke, Alex, Mann, Philipp, McElrath, M Juliana, Odhiambo, Jackline A, Stieh, Daniel J, van Duijn, Janine, Takalani, Azwidihwi N, Willems, Wouter, Tapley, Asa, Tomaras, Georgia D, Van Hoof, Johan, and Schuitemaker, Hanneke
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AIDS vaccines , *VACCINE effectiveness , *INTRAMUSCULAR injections , *VACCINE trials , *PRE-exposure prophylaxis - Abstract
HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa. This randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18–35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7–24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov , NCT03060629 , and is complete. Between Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20–25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7–24 after the first vaccination was 3·38 (95% CI 2·54–4·41) in the vaccine group and 3·94 (3·04–5·03) in the placebo group, with an estimated VE(7–24) of 14·10% (95% CI –22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE. The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1. Division of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Safety and Immunogenicity of a DNA Vaccine With Subtype C gp120 Protein Adjuvanted With MF59 or AS01B: A Phase 1/2a HIV-1 Vaccine Trial.
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Garrett N, Dintwe O, Monaco CL, Jones M, Seaton KE, Church EC, Grunenberg N, Hutter J, deCamp A, Huang Y, Lu H, Mann P, Robinson ST, Heptinstall J, Jensen RL, Pantaleo G, Ding S, Koutsoukos M, Hosseinipour MC, Van Der Meeren O, Gilbert PB, Ferrari G, Andersen-Nissen E, McElrath MJ, Tomaras GD, Gray GE, Corey L, and Kublin JG
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- Humans, Female, Male, Adult, Double-Blind Method, Middle Aged, Young Adult, Adjuvants, Vaccine administration & dosage, South Africa, Immunogenicity, Vaccine, Adolescent, United States, AIDS Vaccines immunology, AIDS Vaccines administration & dosage, AIDS Vaccines adverse effects, Vaccines, DNA immunology, Vaccines, DNA administration & dosage, Vaccines, DNA adverse effects, Squalene administration & dosage, Polysorbates administration & dosage, HIV Envelope Protein gp120 immunology, Adjuvants, Immunologic administration & dosage, HIV-1 immunology, HIV Infections immunology, HIV Infections prevention & control, HIV Antibodies blood
- Abstract
Background: An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B., Methods: HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination., Results: From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose., Conclusions: The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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42. Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study.
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Essink BJ, Shapiro C, Isidro MGD, Bradley P, Pragalos A, Bloch M, Santiaguel J, Frias MV, Miyakis S, Alves de Mesquita M, Berrè S, Servais C, Waugh N, Hoffmann C, Baba E, Schönborn-Kellenberger O, Wolz OO, Koch SD, Ganyani T, Boutet P, Mann P, Mueller SO, Ramanathan R, Gaudinski MR, and Vanhoutte N
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- Humans, Female, Male, Middle Aged, Adult, Vaccines, Synthetic immunology, Vaccines, Synthetic adverse effects, Vaccines, Synthetic administration & dosage, mRNA Vaccines, Lipids, Young Adult, Immunization, Secondary methods, Aged, Nanovaccines, Liposomes, COVID-19 Vaccines immunology, COVID-19 Vaccines adverse effects, COVID-19 Vaccines administration & dosage, COVID-19 prevention & control, COVID-19 immunology, Antibodies, Neutralizing blood, Antibodies, Viral blood, SARS-CoV-2 immunology, Nanoparticles administration & dosage, Immunogenicity, Vaccine, Spike Glycoprotein, Coronavirus immunology
- Abstract
This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 μg. After assessment of safety and immunogenicity of the 12 μg dose in 30 adults, 30 adults ≤ 64 years were randomized to receive either a 3 or 6 μg dose. Solicited adverse events (AEs) were collected for 7 days, unsolicited AEs for 28 days, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) until day (D) 181 post-vaccination. Serum neutralizing titers specific to SARS-CoV-2 BA.1, wild-type, Delta, and additional Omicron subvariants were assessed at D1, D15, D29, D91, and D181. Of 180 vaccinated participants (mean age: 49.3 years; 57.8% women), 70.6% had prior SARS-CoV-2 infection. Most solicited local (98.1%) and systemic (96.7%) AEs were of mild-to-moderate severity; the most common were injection site pain (57.5%; 33.3-73.3% across groups) and myalgia (36.9%; 13.3-56.7%). Unsolicited AEs were reported by 14.4% (6.7-26.7%) of participants (mild-to-moderate severity in 88.5% of the participants). Three participants (1.7%) reported SAEs, 16.7% (6.7-30.0%) reported MAAEs, and 8.3% (0.0-13.3%) reported AESIs (15 COVID-19 cases), none related to vaccination. Geometric means of serum neutralizing titers increased from baseline to D15 and D29 (dose-dependent), and then decreased over time. The safety and immunogenicity results supported advancement to a phase 2 trial.
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- 2024
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