11 results on '"Gelderblom, Huub C."'
Search Results
2. Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study
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Allagappen, Jon, Andriesen, Jessica, Ayres, Alison, Baral, Saman, Bekker, Linda-Gail, Besethi, Asiphe, Borremans, Caroline, Braams, Esmee, Brackett, Caroline, Brumskine, William, Chilengi, Roma, Choi, Rachel, Dubula, Thozama, Dumas, Jaiden Seongmi, Dunn, Brooke, Etikala, Radhika, Euler, Zelda, Everett, Sarah, Garrett, Nigel, Gelderblom, Huub, Gill, Katherine, Gillespie, Kevin, Goedhart, Dimitri, Goosmann, Erik, Grant, Shannon, Hands, Ellie, Haynes, Barton, Herringer, Bronwill, Hoosain, Zaheer, Hosseinipour, Mina, Hunidzarira, Portia, Hutter, Julia, Inambao, Mubiana, Innes, Craig, Keyes, Taylor, Kilembe, William, Kotze, Philippus, Kotze, Sheena, Laher, Fatima, Laszlo, Imre, Lazarus, Erica, Liao, Hua-Xin, Lin, Yong, Lu, Helen, Lucas, Judith, Malahleha, Mookho, McNair, Tara, Meerts, Peter, Mgaga, Zinhle, Montlha, Mahlodi, Mosito, Boitumelo, Moultrie, Andrew, Mudrak, Sarah, Oriol-Mathieu, Valérie, Sarzotti-Kelsoe, Marcella, Mathebula, Matson Tso, Matoga, Mitch, McClennen, Rachael, Mda, Pamela, Naicker, Vimla, Naidoo, Logashvari, Okkers, Cindy-Ann, Omarjee, Saleha, Pasmans, Hella, Philip, Tricia, Pinter, Abraham, Pitsi, Annah, Ramos, Ornelia, Randhawa, April, Roels, Sanne, Rohith, Shamiska, Rutten, Lucy, Sadoff, Jerald, Salinas, Gabriela, Salzgeber, Yvonne, Scheppler, Lorenz, Schwedhelm, Katharine, Schuller, Nicolette, Sharak, Angelina, Stanfield-Oakley, Sherry, Sopher, Carrie, Tafatatha, Terence, Takuva, Simbarashe G., Tang, Chan, Vandebosch, An, Viegas, Edna, Voillet, Valentin, Wegmann, Frank, Weijtens, Mo, Wilcox, Stephany, Williams, Anthony, Yu, Chenchen, Yu, Pei-Chun, Yuan, Olive, Zhang, Xuehan, Kenny, Avi, van Duijn, Janine, Dintwe, One, Heptinstall, Jack, Burnham, Randy, Sawant, Sheetal, Zhang, Lu, Mielke, Dieter, Khuzwayo, Sharon, Omar, Faatima Laher, Goodman, Derrick, Fong, Youyi, Benkeser, David, Zou, Rodger, Hural, John, Hyrien, Ollivier, Juraska, Michal, Luedtke, Alex, van der Laan, Lars, Giorgi, Elena E., Magaret, Craig, Carpp, Lindsay N., Pattacini, Laura, van de Kerkhof, Tom, Korber, Bette, Willems, Wouter, Fisher, Leigh H., Schuitemaker, Hanneke, Swann, Edith, Kublin, James G., Pau, Maria G., Buchbinder, Susan, Tomaka, Frank, Nijs, Steven, Lavreys, Ludo, Gelderblom, Huub C., Corey, Lawrence, Mngadi, Kathryn, Gray, Glenda E., Borducchi, Erica, Hendriks, Jenny, Seaton, Kelly E., Zolla-Pazner, Susan, Barouch, Dan H., Ferrari, Guido, De Rosa, Stephen C., McElrath, M Juliana, Andersen-Nissen, Erica, Stieh, Daniel J., Tomaras, Georgia D., and Gilbert, Peter B.
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- 2024
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3. Application of the SLAPNAP statistical learning tool to broadly neutralizing antibody HIV prevention research
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Williamson, Brian D., Magaret, Craig A., Karuna, Shelly, Carpp, Lindsay N., Gelderblom, Huub C., Huang, Yunda, Benkeser, David, and Gilbert, Peter B.
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- 2023
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4. Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial
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Julg, Boris, Stephenson, Kathryn E., Wagh, Kshitij, Tan, Sabrina C., Zash, Rebecca, Walsh, Stephen, Ansel, Jessica, Kanjilal, Diane, Nkolola, Joseph, Walker-Sperling, Victoria E. K., Ophel, Jasper, Yanosick, Katherine, Borducchi, Erica N., Maxfield, Lori, Abbink, Peter, Peter, Lauren, Yates, Nicole L., Wesley, Martina S., Hassell, Tom, Gelderblom, Huub C., deCamp, Allen, Mayer, Bryan T., Sato, Alicia, Gerber, Monica W., Giorgi, Elena E., Gama, Lucio, Koup, Richard A., Mascola, John R., Monczor, Ana, Lupo, Sofia, Rolle, Charlotte-Paige, Arduino, Roberto, DeJesus, Edwin, Tomaras, Georgia D., Seaman, Michael S., Korber, Bette, and Barouch, Dan H.
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- 2022
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5. Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial
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Stephenson, Kathryn E., Julg, Boris, Tan, C. Sabrina, Zash, Rebecca, Walsh, Stephen R., Rolle, Charlotte-Paige, Monczor, Ana N., Lupo, Sofia, Gelderblom, Huub C., Ansel, Jessica L., Kanjilal, Diane G., Maxfield, Lori F., Nkolola, Joseph, Borducchi, Erica N., Abbink, Peter, Liu, Jinyan, Peter, Lauren, Chandrashekar, Abishek, Nityanandam, Ramya, Lin, Zijin, Setaro, Alessandra, Sapiente, Joseph, Chen, Zhilin, Sunner, Lisa, Cassidy, Tyler, Bennett, Chelsey, Sato, Alicia, Mayer, Bryan, Perelson, Alan S., deCamp, Allan, Priddy, Frances H., Wagh, Kshitij, Giorgi, Elena E., Yates, Nicole L., Arduino, Roberto C., DeJesus, Edwin, Tomaras, Georgia D., Seaman, Michael S., Korber, Bette, and Barouch, Dan H.
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- 2021
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6. Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.
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Mayer, Bryan T., Zhang, Lily, deCamp, Allan C., Yu, Chenchen, Sato, Alicia, Angier, Heather, Seaton, Kelly E., Yates, Nicole, Ledgerwood, Julie E., Mayer, Kenneth, Caskey, Marina, Nussenzweig, Michel, Stephenson, Kathryn, Julg, Boris, Barouch, Dan H., Sobieszczyk, Magdalena E., Edupuganti, Srilatha, Kelley, Colleen F., McElrath, M. Juliana, and Gelderblom, Huub C.
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MONOCLONAL antibodies ,CLINICAL trials ,PHARMACOKINETICS ,MAXIMUM likelihood statistics ,HIV ,HIV antibodies - Abstract
Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Is HIV epidemic control by 2030 realistic?
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Beyrer, Chris, Tomaras, Georgia D, Gelderblom, Huub C, Gray, Glenda E, Janes, Holly E, Bekker, Linda-Gail, Millett, Gregorio, Pantaleo, Giuseppe, Buchbinder, Susan, and Corey, Lawrence
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Rates of new HIV acquisition remain unacceptably high in most populations in low-income, middle-income, and high-income settings despite advances in treatment and prevention strategies. Although biomedical advances in primary prevention of new infections exist, systematic scale-up of these interventions has not occurred at the pace required to end AIDS by 2030. Low population coverage, adherence to oral pre-exposure prophylaxis in settings with high rates of HIV acquisition, and the fact that a significant proportion of new HIV infections occurs in populations not identified as high risk and are hence not targeted for prevention approaches impedes current prevention strategies. Although long-acting injectables and monoclonal antibodies are promising approaches to help reduce incidence, high cost and the need for high coverage rates mean that a vaccine or vaccine-like intervention still remains the most likely scenario to produce a population-level impact on HIV incidence, especially in countries with generalised epidemics. Current global efforts are not sufficient to meet 2030 HIV epidemic goals; acknowledgment of this issue is required to ensure persistent advocacy for population-based control of the ongoing HIV pandemic.
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- 2024
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8. Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.
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Kenny A, van Duijn J, Dintwe O, Heptinstall J, Burnham R, Sawant S, Zhang L, Mielke D, Khuzwayo S, Omar FL, Stanfield-Oakley S, Keyes T, Dunn B, Goodman D, Fong Y, Benkeser D, Zou R, Hural J, Hyrien O, Juraska M, Luedtke A, van der Laan L, Giorgi EE, Magaret C, Carpp LN, Pattacini L, van de Kerkhof T, Korber B, Willems W, Fisher LH, Schuitemaker H, Swann E, Kublin JG, Pau MG, Buchbinder S, Tomaka F, Nijs S, Lavreys L, Gelderblom HC, Corey L, Mngadi K, Gray GE, Borducchi E, Hendriks J, Seaton KE, Zolla-Pazner S, Barouch DH, Ferrari G, De Rosa SC, McElrath MJ, Andersen-Nissen E, Stieh DJ, Tomaras GD, and Gilbert PB
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- Humans, Female, Case-Control Studies, Male, Adult, Vaccine Efficacy, HIV Antibodies blood, HIV Antibodies immunology, Immunoglobulin G blood, Immunoglobulin G immunology, env Gene Products, Human Immunodeficiency Virus immunology, Africa, Southern, Young Adult, Southern African People, AIDS Vaccines immunology, AIDS Vaccines administration & dosage, HIV Infections immunology, HIV Infections prevention & control, HIV Infections virology, HIV-1 immunology
- Abstract
Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models., Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions., Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker., Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen., Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV., Competing Interests: Declaration of interests TvdK has a patent application with Johnson & Johnson and has stocks in Johnson & Johnson. BK received internal support for the present manuscript from her employer (Los Alamos National Laboratory). In the past 36 months, she received support for attending meetings and/or travel from NIH NIAID and from the Gates foundation. Her institution (LANL) had a patent on this work, although she did not receive any personal funds through this patent and was not involved with the licensing of the design to Johnson & Johnson. DHB has a patent on the mosaic HIV vaccine, but no royalties. FT was an employee of Janssen/Johnson & Johnson at the time the work was conducted and owns stock in Johnson & Johnson. LL received support from Janssen Infectious Diseases BV, Beerse, Belgium for travel expenses to attend HIV conferences and has stock or stock options in Johnson & Johnson. JvD, MGP, WW, TvdK and JHen are employees of Janssen/Johnson & Johnson and hold stock or stock options in Johnson & Johnson. WW has a patent planned, issued, or pending with Johnson & Johnson. SCDR had contracts in the past 36 months to perform immunogenicity testing for Janssen, Sanofi, and Moderna. HS and DJS were employees of Janssen Vaccines & Prevention BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. SN was an employee of Janssen Infectious Diseases BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. LP was an employee of Janssen Vaccines & Prevention BV at the time the work was conducted. GDT has received consulting fees for a scientific consulting session. All other authors have no potential competing interests to disclose. Funding for the Imbokodo Study and Correlates Group is the same as listed in “Acknowledgments” for the current work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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