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436 results on '"Bailer, Robert T."'

1. Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials

Author

Happe, Myra, Hofstetter, Amelia R., Wang, Jing, Yamshchikov, Galina V., Holman, LaSonji A., Novik, Laura, Strom, Larisa, Kiweewa, Francis, Wakabi, Salim, Millard, Monica, Kelley, Colleen F., Kabbani, Sarah, Edupuganti, Srilatha, Beck, Allison, Kaltovich, Florence, Murray, Tamar, Tsukerman, Susanna, Carr, Derick, Ashman, Carl, Stanley, Daphne A., Ploquin, Aurélie, Bailer, Robert T., Schwartz, Richard, Cham, Fatim, Tindikahwa, Allan, Hu, Zonghui, Gordon, Ingelise J., Rouphael, Nadine, Houser, Katherine V., Coates, Emily E., Graham, Barney S., Koup, Richard A., Mascola, John R., Sullivan, Nancy J., Robb, Merlin L., Ake, Julie A., Lyke, Kirsten E., Mulligan, Mark J., Ledgerwood, Julie E., and Kibuuka, Hannah

Published
2024
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2. Safety, Tolerability, and Pharmacokinetics of the Broadly Neutralizing Human Immunodeficiency Virus (HIV)-1 Monoclonal Antibody VRC01 in HIV-Exposed Newborn Infants

Author

Cunningham, Coleen K, McFarland, Elizabeth J, Morrison, R Leavitt, Capparelli, Edmund V, Safrit, Jeffrey T, Mofenson, Lynne M, Mathieson, Bonnie, Valentine, Megan E, Perlowski, Charlotte, Smith, Betsy, Hazra, Rohan, Purdue, Lynette, Muresan, Petronella, Harding, Paul A, Mbengeranwa, Tapiwa, Robinson, Lisa-Gaye, Wiznia, Andrew, Theron, Gerhard, Lin, Bob, Bailer, Robert T, Mascola, John R, Graham, Barney S, Aldrovandi, Grace, Bone, Frederic, Dayton, Dale, Johnston, Benjamin, Morgan, Patricia, Myers, Kathryn, Tobin, Nicole, Zimmer, Bonnie, Rossouw, Magdel, Rossouw, Lindie, Louw, Jeanne, Dobroszycki, Joanna, Burey, Marlene, Auguste, Raphaelle, Graham, Kathleen K, Major-Wilson, Hanna, Mhembere, Tsungai, Maturure, Sukunena, Bwakura-Dangarembizi, Mutsa, Barr, Emily, Dunn, Jennifer, Glenny, Carrie, Chambers, Carrie, Baig, Mahboobullah Mirza, Purswani, Murli, Deville, Jaime G, Nielsen-Saines, Karin, Shin, Christina, Carter, Michele F, Chahroudi, Ann, Ahonen, Alexis, Badell, Martina, Chakraborty, Rana, Agwu, Allison, Golden, W Christopher, Anderson, Thuy, Collinson-Streng, Aleisha, Diaz-Velasco, Rodrigo, Rosario, Nicolas, Pérez, Elvia, Marrero, Wanda I, Febo, Irma, Santos, Ruth, and Zorrilla, Carmen D

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Prevention, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric AIDS, HIV/AIDS, Pediatric, Clinical Research, Immunization, Vaccine Related, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Reproductive health and childbirth, Good Health and Well Being, Africa, Antibodies, Monoclonal, Broadly Neutralizing Antibodies, Female, HIV Antibodies, HIV Infections, HIV-1, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical, Injections, Subcutaneous, Linear Models, Male, United States, broadly neutralizing antibodies, mother-to-child transmission of HIV, neonates, VRC01, IMPAACT P1112 team, Biological Sciences, Medical and Health Sciences, Microbiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAlthough mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission.MethodsA Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis.ResultsForty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1-6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding.ConclusionsSubcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants.

Published
2020

3. Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope

Author

Schoofs, Till, Barnes, Christopher O, Suh-Toma, Nina, Golijanin, Jovana, Schommers, Philipp, Gruell, Henning, West, Anthony P, Bach, Franziska, Lee, Yu Erica, Nogueira, Lilian, Georgiev, Ivelin S, Bailer, Robert T, Czartoski, Julie, Mascola, John R, Seaman, Michael S, McElrath, M Juliana, Doria-Rose, Nicole A, Klein, Florian, Nussenzweig, Michel C, and Bjorkman, Pamela J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Immunization, Vaccine Related, Vaccine Related (AIDS), HIV/AIDS, Prevention, Infection, Good Health and Well Being, Amino Acid Sequence, Antibodies, Neutralizing, Antibody Affinity, B-Lymphocytes, Epitopes, Glycosylation, HIV Antibodies, HIV Envelope Protein gp120, HIV Infections, HIV-1, Humans, Models, Molecular, Phylogeny, Polysaccharides, Protein Binding, Protein Conformation, env Gene Products, Human Immunodeficiency Virus, Env trimer, HIV-1 Env silent face, HIV-1 vaccine, broadly neutralizing antibody, cryo-EM, glycan recognition, humanized mice, immunotherapy
Abstract

Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448gp120 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.

Published
2019

4. Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial

Author

Houser, Katherine V., Chen, Grace L., Carter, Cristina, Crank, Michelle C., Nguyen, Thuy A., Burgos Florez, Maria Claudia, Berkowitz, Nina M., Mendoza, Floreliz, Hendel, Cynthia Starr, Gordon, Ingelise J., Coates, Emily E., Vazquez, Sandra, Stein, Judy, Case, Christopher L., Lawlor, Heather, Carlton, Kevin, Gaudinski, Martin R., Strom, Larisa, Hofstetter, Amelia R., Liang, C. Jason, Narpala, Sandeep, Hatcher, Christian, Gillespie, Rebecca A., Creanga, Adrian, Kanekiyo, Masaru, Raab, Julie E., Andrews, Sarah F., Zhang, Yi, Yang, Eun Sung, Wang, Lingshu, Leung, Kwanyee, Kong, Wing-Pui, Freyn, Alec W., Nachbagauer, Raffael, Palese, Peter, Bailer, Robert T., McDermott, Adrian B., Koup, Richard A., Gall, Jason G., Arnold, Frank, Mascola, John R., Graham, Barney S., and Ledgerwood, Julie E.

Published
2022
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5. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting.

Author

Doria-Rose, Nicole A, Altae-Tran, Han R, Roark, Ryan S, Schmidt, Stephen D, Sutton, Matthew S, Louder, Mark K, Chuang, Gwo-Yu, Bailer, Robert T, Cortez, Valerie, Kong, Rui, McKee, Krisha, O'Dell, Sijy, Wang, Felicia, Abdool Karim, Salim S, Binley, James M, Connors, Mark, Haynes, Barton F, Martin, Malcolm A, Montefiori, David C, Morris, Lynn, Overbaugh, Julie, Kwong, Peter D, Mascola, John R, and Georgiev, Ivelin S

Subjects
Humans, HIV-1, HIV Infections, AIDS Vaccines, HIV Antibodies, Epitopes, Neutralization Tests, Cohort Studies, Epitope Mapping, Antibody Formation, Antibody Specificity, Algorithms, Computer Simulation, Microbiology, Immunology, Medical Microbiology, Virology
Abstract

Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities. At the individual donor level, the next-generation NFP algorithms particularly improved the ability to detect multiple epitope specificities in a sample, as confirmed both for computationally simulated polyclonal sera and for samples from HIV-infected donors. Specifically, the next-generation NFP algorithms detected multiple specificities in twice as many samples of simulated sera. Further, unlike the first-generation NFP, the new algorithms were able to detect both of the previously confirmed antibody specificities, VRC01-like and PG9-like, in donor CHAVI 0219. At the cohort level, analysis of ~150 broadly neutralizing HIV-infected donor samples suggested a potential connection between clade of infection and types of elicited epitope specificities. Most notably, while 10E8-like antibodies were observed in infections from different clades, an enrichment of such antibodies was predicted for clade B samples. Ultimately, such large-scale analyses of antibody responses to HIV-1 infection can help guide the design of epitope-specific vaccines that are tailored to take into account the prevalence of infecting clades within a specific geographic region. Overall, the next-generation NFP technology will be an important tool for the analysis of broadly neutralizing polyclonal antibody responses against HIV-1.

Published
2017

6. Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound

Author

Cale, Evan M., Bai, Hongjun, Bose, Meera, Messina, Michael A., Colby, Donn J., Sanders-Buell, Eric, Dearlove, Bethany, Li, Yifan, Engeman, Emily, Silas, Daniel, O'Sullivan, Anne Marie, Mann, Brendan, Pinyakorn, Suteeraporn, Intasan, Jintana, Benjapornpong, Khunthalee, Sacdalan, Carlo, Kroon, Eugene, Phanuphak, Nittaya, Gramzinski, Robert, Vasan, Sandhya, Robb, Merlin L., Michael, Nelson L., Lynch, Rebecca M., Bailer, Robert T., Pagliuzza, Amelie, Chomont, Nicolas, Pegu, Amarendra, Doria-Rose, Nicole A., Trautmann, Lydie, Crowell, Trevor A., Mascola, John R., Ananworanich, Jintanat, Tovanabutra, Sodsai, and Rolland, Morgane

Subjects
Highly active antiretroviral therapy -- Health aspects, HIV -- Genetic aspects -- Prevention, Antiretroviral agents -- Health aspects, Antibodies -- Genetic aspects -- Health aspects, Antigenic determinants -- Genetic aspects -- Health aspects, Health care industry
Abstract

Infusion of the broadly neutralizing antibody VRC01 has been evaluated in individuals chronically infected with HIV-1. Here, we studied how VRC01 infusions affected viral rebound after cessation of antiretroviral therapy (ART) in 18 acutely treated and durably suppressed individuals. Viral rebound occurred in all individuals, yet VRC01 infusions modestly delayed rebound and participants who showed a faster decay of VRC01 in serum rebounded more rapidly. Participants with strains most sensitive to VRC01 or with VRC01 epitope motifs similar to known VRC01- susceptible strains rebounded later. Upon rebound, HIV-1 sequences were indistinguishable from those sampled at diagnosis. Across the cohort, participant-derived Env showed different sensitivity to VRC01 neutralization (including 2 resistant viruses), yet neutralization sensitivity was similar at diagnosis and after rebound, indicating the lack of selection for VRC01 resistance during treatment interruption. Our results showed that viremia rebounded despite the absence of HIV-1 adaptation to VRC01 and an average VRC01 trough of 221 micro]g/mL. Although VRC01 levels were insufficient to prevent a resurgent infection, knowledge that they did not mediate Env mutations in acute-like viruses is relevant for antibody-based strategies in acute infection., Introduction Analytic treatment interruption (ATI) studies can help evaluate strategies to mediate long-term remission in HIV-1-infected persons. An ATI study tested the impact of the administration of the broadly neutralizing [...]

Published
2020
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7. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial

Author

Mendoza, Floreliz, Novik, Laura, Zephir, Kathy, Whalen, William, Larkin, Brenda, Saunders, Jamie, Cunningham, Jennifer, Levinson, Carol, Wang, Xiaolin, Plummer, Sarah, Victorino, Milalynn, Ola, Abidemi, Boyd, Catina, Jayasinghe, Nilusha, Apte, Preeti, Cartagena, Cora Trelles, Hicks, Renunda, Williams, Pernell, Vasilenko, Olga, Yamshchikov, Galina, Florez, Maria Burgos, Pittman, Iris, Gama, Lucio, Casazza, Joseph, DeCederfelt, Hope, Cheng, KC, Stein, Judy, Gaudinski, Martin R, Houser, Katherine V, Doria-Rose, Nicole A, Chen, Grace L, Rothwell, Ro Shauna S, Berkowitz, Nina, Costner, Pamela, Holman, LaSonji A, Gordon, Ingelise J, Hendel, Cynthia S, Kaltovich, Florence, Conan-Cibotti, Michelle, Gomez Lorenzo, Margarita, Carter, Cristina, Sitar, Sandra, Carlton, Kevin, Gall, Jason, Laurencot, Carolyn, Lin, Bob C, Bailer, Robert T, McDermott, Adrian B, Ko, Sung-Youl, Pegu, Amarendra, Kwon, Young D, Kwong, Peter D, Namboodiri, Aryan M, Pandey, Janardan P, Schwartz, Richard, Arnold, Frank, Hu, Zonghui, Zhang, Lily, Huang, Yunda, Koup, Richard A, Capparelli, Edmund V, Graham, Barney S, Mascola, John R, and Ledgerwood, Julie E

Published
2019
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8. Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial

Author

Ake, Julie A., Akapirat, Siriwat, Bose, Meera, Cale, Evan, Chan, Phillip, Chanthaburanun, Sararut, Churikanont, Nampueng, Dawson, Peter, Dumrongpisutikul, Netsiri, Getchalarat, Saowanit, Jongrakthaitae, Surat, Jongsakul, Krisada, Lerdlum, Sukalaya, Manasnayakorn, Sopark, McCullough, Corinne, Milazzo, Mark, Nuntapinit, Bessara, On, Kier, Ouellette, Madelaine, Phanuphak, Praphan, Sanders-Buell, Eric, Sangnoi, Nongluck, Shangguan, Shida, Sirivichayakul, Sunee, Tragonlugsana, Nipattra, Trichavaroj, Rapee, Ubolyam, Sasiwimol, Vasan, Sandhya, Wattanaboonyongcharoen, Phandee, Yamchuenpong, Thipvadee, Crowell, Trevor A, Colby, Donn J, Pinyakorn, Suteeraporn, Sacdalan, Carlo, Pagliuzza, Amélie, Intasan, Jintana, Benjapornpong, Khunthalee, Tangnaree, Kamonkan, Chomchey, Nitiya, Kroon, Eugène, de Souza, Mark S, Tovanabutra, Sodsai, Rolland, Morgane, Eller, Michael A, Paquin-Proulx, Dominic, Bolton, Diane L, Tokarev, Andrey, Thomas, Rasmi, Takata, Hiroshi, Trautmann, Lydie, Krebs, Shelly J, Modjarrad, Kayvon, McDermott, Adrian B, Bailer, Robert T, Doria-Rose, Nicole, Patel, Bijal, Gorelick, Robert J, Fullmer, Brandie A, Schuetz, Alexandra, Grandin, Pornsuk V, O'Connell, Robert J, Ledgerwood, Julie E, Graham, Barney S, Tressler, Randall, Mascola, John R, Chomont, Nicolas, Michael, Nelson L, Robb, Merlin L, Phanuphak, Nittaya, and Ananworanich, Jintanat

Published
2019
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9. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials

Author

Plummer, Sarah, Costner, Pamela, Zephir, Kathryn, Casazza, Joseph, Ola, Abidemi, Victorino, Milalynn, Levinson, Carol, Whalen, William, Wang, Xiaolin, Cunningham, Jennifer, Vasilenko, Olga, Burgos Florez, Maria, Hickman, Somia, Pittman, Iris, Le, Lam, Larkin, Brenda, Andrews, Charla, Apte, Preeti, Hicks, Renunda, Trelles Cartagena, Cora, Williams, Pernell, Boyd, Catina R, Conan-Cibotti, Michelle, Stein, Judy, Kaltovich, Florence, DeCederfelt, Hope, McAdams, Stacey, Renehan, Phyllis, Chen, Wilbur, Greenberg, Nancy, Wymer, Nancy, Wadsworth, Linda, Billington, Melissa, Robinson, Toni, Boyce, Colleen, Pa'ahana Brown, Faith, Chrisley, Lisa, Kwon, Alyson, Patel, Prashant, Kominou, Panagoita, Dorsey, Brenda, Eddington, Staci, Telscher, Shinyi, Lee, Myoughee, Mosely, Regina, Ross, April, Ford, Geoffrey, Domjahn, Briyana, Xu, Jianguo, Beck, Allison, Fineman, Rebecca, Heeke, Shiela, Winter, Jean, Nagar, Shashi, Kelley, Colleen, Mulligan, Mark, Gaudinski, Martin R, Houser, Katherine V, Morabito, Kaitlyn M, Hu, Zonghui, Yamshchikov, Galina, Rothwell, Ro Shauna, Berkowitz, Nina, Mendoza, Floreliz, Saunders, Jamie G, Novik, Laura, Hendel, Cynthia S, Holman, LaSonji A, Gordon, Ingelise J, Cox, Josephine H, Edupuganti, Srilatha, McArthur, Monica A, Rouphael, Nadine G, Lyke, Kirsten E, Cummings, Ginny E, Sitar, Sandra, Bailer, Robert T, Foreman, Bryant M, Burgomaster, Katherine, Pelc, Rebecca S, Gordon, David N, DeMaso, Christina R, Dowd, Kimberly A, Laurencot, Carolyn, Schwartz, Richard M, Mascola, John R, Graham, Barney S, Pierson, Theodore C, Ledgerwood, Julie E, and Chen, Grace L

Published
2018
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10. Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1

Author

Xu, Kai, Acharya, Priyamvada, Kong, Rui, Cheng, Cheng, Chuang, Gwo-Yu, Liu, Kevin, Louder, Mark K., O’Dell, Sijy, Rawi, Reda, Sastry, Mallika, Shen, Chen-Hsiang, Zhang, Baoshan, Zhou, Tongqing, Asokan, Mangaiarkarasi, Bailer, Robert T., Chambers, Michael, Chen, Xuejun, Choi, Chang W., Dandey, Venkata P., Doria-Rose, Nicole A., Druz, Aliaksandr, Eng, Edward T., Farney, S. Katie, Foulds, Kathryn E., Geng, Hui, Georgiev, Ivelin S., Gorman, Jason, Hill, Kurt R., Jafari, Alexander J., Kwon, Young D., Lai, Yen-Ting, Lemmin, Thomas, McKee, Krisha, Ohr, Tiffany Y., Ou, Li, Peng, Dongjun, Rowshan, Ariana P., Sheng, Zizhang, Todd, John-Paul, Tsybovsky, Yaroslav, Viox, Elise G., Wang, Yiran, Wei, Hui, Yang, Yongping, Zhou, Amy F., Chen, Rui, Yang, Lu, Scorpio, Diana G., McDermott, Adrian B., Shapiro, Lawrence, Carragher, Bridget, Potter, Clinton S., Mascola, John R., and Kwong, Peter D.

Published
2018
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11. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

Author

Kong, Rui, Xu, Kai, Zhou, Tongqing, Acharya, Priyamvada, Lemmin, Thomas, Liu, Kevin, Ozorowski, Gabriel, Soto, Cinque, Taft, Justin D., Bailer, Robert T., Cale, Evan M., Chen, Lei, Choi, Chang W., Chuang, Gwo-Yu, Doria-Rose, Nicole A., Druz, Aliaksandr, Georgiev, Ivelin S., Gorman, Jason, Huang, Jinghe, Joyce, M. Gordon, Louder, Mark K., Ma, Xiaochu, McKee, Krisha, O'Dell, Sijy, Pancera, Marie, Yang, Yongping, Blanchard, Scott C., Mothes, Walther, Burton, Dennis R., Koff, Wayne C., Connors, Mark, Ward, Andrew B., Kwong, Peter D., and Mascola, John R.

Published
2016

12. Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry

Author

Lai, Yen-Ting, Wang, Tao, O’Dell, Sijy, Louder, Mark K., Schön, Arne, Cheung, Crystal S. F., Chuang, Gwo-Yu, Druz, Aliaksandr, Lin, Bob, McKee, Krisha, Peng, Dongjun, Yang, Yongping, Zhang, Baoshan, Herschhorn, Alon, Sodroski, Joseph, Bailer, Robert T., Doria-Rose, Nicole A., Mascola, John R., Langley, David R., and Kwong, Peter D.

Published
2019
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13. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial

Author

Kibuuka, Hannah, Berkowitz, Nina M, Millard, Monica, Enama, Mary E, Tindikahwa, Allan, Sekiziyivu, Arthur B, Costner, Pamela, Sitar, Sandra, Glover, Deline, Hu, Zonghui, Joshi, Gyan, Stanley, Daphne, Kunchai, Meghan, Eller, Leigh Anne, Bailer, Robert T, Koup, Richard A, Nabel, Gary J, Mascola, John R, Sullivan, Nancy J, Graham, Barney S, Roederer, Mario, Michael, Nelson L, Robb, Merlin L, and Ledgerwood, Julie E

Published
2015
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15. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial

Author

Chang, Lee-Jah, Dowd, Kimberly A, Mendoza, Floreliz H, Saunders, Jamie G, Sitar, Sandra, Plummer, Sarah H, Yamshchikov, Galina, Sarwar, Uzma N, Hu, Zonghui, Enama, Mary E, Bailer, Robert T, Koup, Richard A, Schwartz, Richard M, Akahata, Wataru, Nabel, Gary J, Mascola, John R, Pierson, Theodore C, Graham, Barney S, and Ledgerwood, Julie E

Published
2014
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16. Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge

Author

Julg, Boris, Tartaglia, Lawrence J., Keele, Brandon F., Wagh, Kshitij, Pegu, Amarendra, Sok, Devin, Abbink, Peter, Schmidt, Stephen D., Wang, Keyun, Chen, Xuejun, Gordon Joyce, M., Georgiev, Ivelin S., Choe, Misook, Kwong, Peter D., Doria-Rose, Nicole A., Le, Khoa, Louder, Mark K., Bailer, Robert T., Moore, Penny L., Korber, Bette, Seaman, Michael S., Abdool Karim, Salim S., Morris, Lynn, Koup, Richard A., Mascola, John R., Burton, Dennis R., and Barouch, Dan H.

Published
2017
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17. Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide

Author

Alam, S. Munir, Aussedat, Baptiste, Vohra, Yusuf, Ryan Meyerhoff, R., Cale, Evan M., Walkowicz, William E., Radakovich, Nathan A., Anasti, Kara, Armand, Lawrence, Parks, Robert, Sutherland, Laura, Scearce, Richard, Joyce, M. Gordon, Pancera, Marie, Druz, Aliaksandr, Georgiev, Ivelin S., Von Holle, Tarra, Eaton, Amanda, Fox, Christopher, Reed, Steven G., Louder, Mark, Bailer, Robert T., Morris, Lynn, Abdool-Karim, Salim S., Cohen, Myron, Liao, Hua-Xin, Montefiori, David C., Park, Peter K., Fernández-Tejada, Alberto, Wiehe, Kevin, Santra, Sampa, Kepler, Thomas B., Saunders, Kevin O., Sodroski, Joseph, Kwong, Peter D., Mascola, John R., Bonsignori, Mattia, Moody, M. Anthony, Danishefsky, Samuel, and Haynes, Barton F.

Published
2017
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18. Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

Author

Bonsignori, Mattia, Kreider, Edward F., Fera, Daniela, Meyerhoff, R. Ryan, Bradley, Todd, Wiehe, Kevin, Alam, S. Munir, Aussedat, Baptiste, Walkowicz, William E., Hwang, Kwan-Ki, Saunders, Kevin O., Zhang, Ruijun, Gladden, Morgan A., Monroe, Anthony, Kumar, Amit, Xia, Shi-Mao, Cooper, Melissa, Louder, Mark K., McKee, Krisha, Bailer, Robert T., Pier, Brendan W., Jette, Claudia A., Kelsoe, Garnett, Williams, Wilton B., Morris, Lynn, Kappes, John, Wagh, Kshitij, Kamanga, Gift, Cohen, Myron S., Hraber, Peter T., Montefiori, David C., Trama, Ashley, Liao, Hua-Xin, Kepler, Thomas B., Moody, M. Anthony, Gao, Feng, Danishefsky, Samuel J., Mascola, John R., Shaw, George M., Hahn, Beatrice H., Harrison, Stephen C., Korber, Bette T., and Haynes, Barton F.

Published
2017
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19. Supplemental Materials for Safety and Immunogenicity of Chimpanzee Adenovirus Vector Ebola Vaccine

Author

Ledgerwood, Julie E., DeZure, Adam D., Stanley, Daphne A., Novik, Laura, Enama, Mary E., Berkowitz, Nina M., Hu, Zonghui, Joshi, Gyan, Ploquin, Aurélie, Sitar, Sandra, Gordon, Ingelise J., Plummer, Sarah A., Holman, LaSonji A., Hendel, Cynthia S., Yamshchikov, Galina, Roman, Francois, Nicosia, Alfredo, Colloca, Stefano, Cortese, Riccardo, Bailer, Robert T., Schwartz, Richard M., Roederer, Mario, Mascola, John R., Koup, Richard A., Sullivan, Nancy J., and Graham, Barney S.

Published
2017

20. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma

Author

Williams, LaTonya D., Ofek, Gilad, Schätzle, Sebastian, McDaniel, Jonathan R., Lu, Xiaozhi, Nicely, Nathan I., Wu, Liming, Lougheed, Caleb S., Bradley, Todd, Louder, Mark K., McKee, Krisha, Bailer, Robert T., O’Dell, Sijy, Georgiev, Ivelin S., Seaman, Michael S., Parks, Robert J., Marshall, Dawn J., Anasti, Kara, Yang, Guang, Nie, Xiaoyan, Tumba, Nancy L., Wiehe, Kevin, Wagh, Kshitij, Korber, Bette, Kepler, Thomas B., Munir Alam, S., Morris, Lynn, Kamanga, Gift, Cohen, Myron S., Bonsignori, Mattia, Xia, Shi-Mao, Montefiori, David C., Kelsoe, Garnett, Gao, Feng, Mascola, John R., Moody, M. Anthony, Saunders, Kevin O., Liao, Hua-Xin, Tomaras, Georgia D., Georgiou, George, and Haynes, Barton F.

Published
2017
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23. Therapeutic Vaccination Expands and Improves the Function of the HIV-Specific Memory T-Cell Repertoire

Author

VRC 101 Study Team, Casazza, Joseph P., Bowman, Kathryn A., Adzaku, Selorm, Smith, Emily C., Enama, Mary E., Bailer, Robert T., Price, David A., Gostick, Emma, Gordon, Ingelise J., Ambrozak, David R., Nason, Martha C., Roederer, Mario, Andrews, Charla A., Maldarelli, Frank M., Wiegand, Ann, Kearney, Mary F., Persaud, Deborah, Ziemniak, Carrie, Gottardo, Raphael, Ledgerwood, Julie E., Graham, Barney S., and Koup, Richard A.

Published
2013
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24. Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization

Author

Georgiev, Ivelin S., Doria-Rose, Nicole A., Zhou, Tongqing, Kwon, Young Do, Staupe, Ryan P., Moquin, Stephanie, Chuang, Gwo-Yu, Louder, Mark K., Schmidt, Stephen D., Altae-Tran, Han R., Bailer, Robert T., McKee, Krisha, Nason, Martha, O'Dell, Sijy, Ofek, Gilad, Pancera, Marie, Srivatsan, Sanjay, Shapiro, Lawrence, Connors, Mark, Migueles, Stephen A., Morris, Lynn, Nishimura, Yoshiaki, Martin, Malcolm A., Mascola, John R., and Kwong, Peter D.

Published
2013
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25. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques

Author

Xu, Ling, Pegu, Amarendra, Rao, Ercole, Doria-Rose, Nicole, Beninga, Jochen, McKee, Krisha, Lord, Dana M., Wei, Ronnie R., Deng, Gejing, Louder, Mark, Schmidt, Stephen D., Mankoff, Zachary, Wu, Lan, Asokan, Mangaiarkarasi, Beil, Christian, Lange, Christian, Leuschner, Wulf Dirk, Kruip, Jochen, Sendak, Rebecca, Do Kwon, Young, Zhou, Tongqing, Chen, Xuejun, Bailer, Robert T., Wang, Keyun, Choe, Misook, Tartaglia, Lawrence J., Barouch, Dan H., OʼDell, Sijy, Todd, John-Paul, Burton, Dennis R., Roederer, Mario, Connors, Mark, Koup, Richard A., Kwong, Peter D., Yang, Zhi-yong, Mascola, John R., and Nabel, Gary J.

Published
2017
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26. Chimpanzee Adenovirus Vector Ebola Vaccine

Author

Ledgerwood, Julie E., DeZure, Adam D., Stanley, Daphne A., Coates, Emily E., Novik, Laura, Enama, Mary E., Berkowitz, Nina M., Hu, Zonghui, Joshi, Gyan, Ploquin, Aurélie, Sitar, Sandra, Gordon, Ingelise J., Plummer, Sarah A., Holman, LaSonji A., Hendel, Cynthia S., Yamshchikov, Galina, Roman, Francois, Nicosia, Alfredo, Colloca, Stefano, Cortese, Riccardo, Bailer, Robert T., Schwartz, Richard M., Roederer, Mario, Mascola, John R., Koup, Richard A., Sullivan, Nancy J., and Graham, Barney S.

Published
2017
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28. An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial

Author

DeZure, Adam D., Coates, Emily E., Hu, Zonghui, Yamshchikov, Galina V., Zephir, Kathryn L., Enama, Mary E., Plummer, Sarah H., Gordon, Ingelise J., Kaltovich, Florence, Andrews, Sarah, McDermott, Adrian, Crank, Michelle C., Koup, Richard A, Schwartz, Richard M., Bailer, Robert T., Sun, Xiangjie, Mascola, John R., Tumpey, Terrence M., Graham, Barney S., and Ledgerwood, Julie E.

Published
2017
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29. A West Nile Virus DNA Vaccine Induces Neutralizing Antibody in Healthy Adults during a Phase 1 Clinical Trial

Author

Vaccine Research Center 302 Study Team, Martin, Julie E., Pierson, Theodore C., Hubka, Sarah, Rucker, Steve, Gordon, Ingelise J., Enama, Mary E., Andrews, Charla A., Xu, Qing, Davis, Brent S., Nason, Martha C., Fay, Michael P., Koup, Richard A., Roederer, Mario, Bailer, Robert T., Gomez, Phillip L., Mascola, John R., Chang, Gwong-Jen J., Nabel, Gary J., and Graham, Barney S.

Published
2007
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31. Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV-1 Candidate Vaccine Delivered by a Replication-Defective Recombinant Adenovirus Vector

Author

The Vaccine Research Center 006 Study Team, Catanzaro, Andrew T., Koup, Richard A., Roederer, Mario, Bailer, Robert T., Enama, Mary E., Moodie, Zoe, Gu, Lin, Martin, Julie E., Novik, Laura, Chakrabarti, Bimal K., Butman, Bryan T., Gall, Jason G. D., King, Richter, Andrews, Charla A., Sheets, Rebecca, Gomez, Phillip L., Mascola, John R., Nabel, Gary J., and Graham, Barney S.

Published
2006

32. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

Author

Huang, Jinghe, Kang, Byong H., Pancera, Marie, Lee, Jeong Hyun, Tong, Tommy, Feng, Yu, Imamichi, Hiromi, Georgiev, Ivelin S., Chuang, Gwo-Yu, Druz, Aliaksandr, Doria-Rose, Nicole A., Laub, Leo, Sliepen, Kwinten, van Gils, Marit J., de la Pena, Alba Torrents, Derking, Ronald, Klasse, Per-Johan, Migueles, Stephen A., Bailer, Robert T., Alam, Munir, Pugach, Pavel, Haynes, Barton F., Wyatt, Richard T., Sanders, Rogier W., Binley, James M., Ward, Andrew B., Mascola, John R., Kwong, Peter D., and Connors, Mark

Subjects
Viral antibodies -- Physiological aspects -- Research, Antigenic determinants -- Physiological aspects -- Research, Antibodies -- Physiological aspects -- Research, HIV infection -- Genetic aspects -- Care and treatment -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration ([IC.sub.50]), Induction of a potent neutralizing antibody response capable of recognizing highly diverse isolates of HIV-1 is one of the most important goals of HIV vaccine research. This represents a considerable [...]

Published
2014

33. Structure and immune recognition of trimeric pre-fusion HIV-1 Env

Author

Pancera, Marie, Zhou, Tongqing, Druz, Aliaksandr, Georgiev, Ivelin S., Soto, Cinque, Gorman, Jason, Huang, Jinghe, Acharya, Priyamvada, Chuang, Gwo-Yu, Ofek, Gilad, Stewart-Jones, Guillaume B.E., Stuckey, Jonathan, Bailer, Robert T., Joyce, M. Gordon, Louder, Mark K., Tumba, Nancy, Yang, Yongping, Zhang, Baoshan, Cohen, Myron S., Haynes, Barton F., Mascola, John R., Morris, Lynn, Munro, James B., Blanchard, Scott C., Mothes, Walther, Connors, Mark, and Kwong, Peter D.

Subjects
HIV antibodies -- Physiological aspects, Viral proteins -- Structure -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 sub-units, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 A resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the prefusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy- terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence- variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation., Over the last 50 years, more than 70 million people have been infected or killed by the human immunodeficiency virus type 1 (HIV-1) (1). A dominant contributing factor has been [...]

Published
2014
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34. Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV

Author

Roederer, Mario, Keele, Brandon F., Schmidt, Stephen D., Mason, Rosemarie D., Welles, Hugh C., Fischer, Will, Labranche, Celia, Foulds, Kathryn E., Louder, Mark K., Yang, Zhi-Yong, Todd, John-Paul M., Buzby, Adam P., Mach, Linh V., Shen, Ling, Seaton, Kelly E., Ward, Brandy M., Bailer, Robert T., Gottardo, Raphael, Gu, Wenjuan, Ferrari, Guido, Alam, S. Munir, Denny, Thomas N., Montefiori, David C., Tomaras, Georgia D., Korber, Bette T., Nason, Martha C., Seder, Robert A., Koup, Richard A., Letvin, Norman L., Rao, Srinivas S., Nabel, Gary J., and Mascola, John R.

Subjects
Antigen-antibody reactions -- Research, Immune complexes -- Research, AIDS (Disease) -- Research, AIDS research, Monoclonal antibodies -- Health aspects -- Analysis -- Physiological aspects, AIDS vaccines -- Health aspects -- Analysis -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials., Among the five human efficacy trials of HIV-1 vaccines, only one has shown some success in preventing HIV infection. In the RV144 trial, a combination viral vector and protein immunization [...]

Published
2014
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35. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults

Author

Gaudinski, Martin R., Coates, Emily E., Houser, Katherine V., Chen, Grace L., Yamshchikov, Galina, Saunders, Jamie G., Holman, LaSonji A., Gordon, Ingelise, Plummer, Sarah, Hendel, Cynthia S., Conan-Cibotti, Michelle, Lorenzo, Margarita Gomez, Sitar, Sandra, Carlton, Kevin, Laurencot, Carolyn, Bailer, Robert T., Narpala, Sandeep, McDermott, Adrian B., Namboodiri, Aryan M., Pandey, Janardan P., Schwartz, Richard M., Hu, Zonghui, Koup, Richard A., Capparelli, Edmund, Graham, Barney S., Mascola, John R., and Ledgerwood, Julie E.

Subjects
United States. National Institutes of Health, HIV (Viruses) -- Research -- Drug therapy -- Prevention, Clinical trials -- Analysis, Adults -- Health aspects, Vaccines -- Health aspects, Monoclonal antibodies -- Health aspects, HIV infection -- Health aspects -- Prevention, Biological sciences
Abstract

Background VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb) against the CD4-binding site of the HIV-1 envelope glycoprotein (Env) that is currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial. VRC01LS is a modified version of VRC01, designed for extended serum half-life by increased binding affinity to the neonatal Fc receptor. Methods and findings This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was conducted by the Vaccine Research Center (VRC) at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD). The age range of the study volunteers was 21-50 years; 51% of study volunteers were male and 49% were female. Primary objectives were safety and tolerability of VRC01LS intravenous (IV) infusions at 5, 20, and 40 mg/kg infused once, 20 mg/kg given three times at 12-week intervals, and subcutaneous (SC) delivery at 5 mg/kg delivered once, or three times at 12-week intervals. Secondary objectives were pharmacokinetics (PK), serum neutralization activity, and development of antidrug antibodies. Enrollment began on November 16, 2015, and concluded on August 23, 2017. This report describes the safety data for the first 37 volunteers who received administrations of VRC01LS. There were no serious adverse events (SAEs) or dose-limiting toxicities. Mild malaise and myalgia were the most common adverse events (AEs). There were six AEs assessed as possibly related to VRC01LS administration, and all were mild in severity and resolved during the study. PK data were modeled based on the first dose of VRC01LS in the first 25 volunteers to complete their schedule of evaluations. The mean (±SD) serum concentration 12 weeks after one IV administration of 20 mg/kg or 40 mg/kg were 180 ± 43 [mu]g/mL (n = 7) and 326 ± 35 [mu]g/mL (n = 5), respectively. The mean (±SD) serum concentration 12 weeks after one IV and SC administration of 5 mg/kg were 40 ± 3 [mu]g/mL (n = 2) and 25 ± 5 [mu]g/mL (n = 9), respectively. Over the 5-40 mg/kg IV dose range (n = 16), the clearance was 36 ± 8 mL/d with an elimination half-life of 71 ± 18 days. VRC01LS retained its expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. Potential limitations of this study include the small sample size typical of Phase I trials and the need to further describe the PK properties of VRC01LS administered on multiple occasions. Conclusions The human bnMAb VRC01LS was safe and well tolerated when delivered intravenously or subcutaneously. The half-life was more than 4-fold greater when compared to wild-type VRC01 historical data. The reduced clearance and extended half-life may make it possible to achieve therapeutic levels with less frequent and lower-dose administrations. This would potentially lower the costs of manufacturing and improve the practicality of using passively administered monoclonal antibodies (mAbs) for the prevention of HIV-1 infection. Trial registration ClinicalTrials.gov NCT02599896, Author(s): Martin R. Gaudinski 1, Emily E. Coates 1, Katherine V. Houser 1, Grace L. Chen 1, Galina Yamshchikov 1, Jamie G. Saunders 1, LaSonji A. Holman 1, Ingelise Gordon [...]

Published
2018
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37. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody

Author

Huang, Jinghe, Ofek, Gilad, Laub, Leo, Louder, Mark K., Doria-Rose, Nicole A., Longo, Nancy S., Imamichi, Hiromi, Bailer, Robert T., Chakrabarti, Bimal, Sharma, Shailendra K., Alam, S. Munir, Wang, Tao, Yang, Yongping, Zhang, Baoshan, Migueles, Stephen A., Wyatt, Richard, Haynes, Barton F., Kwong, Peter D., Mascola, John R., and Connors, Mark

Published
2012
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38. Immune Correlates Analysis of an HIV-1 Vaccine Efficacy Trial

Author

Haynes, Barton F., Gilbert, Peter B., Juliana McElrath, M., Zolla-Pazner, Susan, Tomaras, Georgia D., Munir Alam, S., Evans, David, Montefiori, David, Karnasuta, Chitraporn, Sutthent, Ruengpueng, Liao, Hua-Xin, DeVico, Anthony, Lewis, George, Williams, Constance, Pinter, Abraham, Fong, Youyi, Janes, Holly, DeCamp, Allan, Huang, Yunda, Rao, Mangala, Billings, Erik, Karasavvas, Nicos, Robb, Merlin L., Ngauy, Viseth, de Souza, Mark S., Paris, Robert, Ferrari, Guido, Bailer, Robert T., Soderberg, Kelly A., Andrews, Charla, Berman, Phillip, Frahm, Nicole, De Rosa, Stephen C., Alpert, Michael D., Yates, Nicole L., Shen, Xiaoying, Koup, Richard A., Pitisuttithum, Punnee, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Rerks-Ngarm, Supachai, Michael, Nelson L., and Kim, Jerome H.

Published
2012

40. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies

Author

Doria-Rose, Nicole A., Schramm, Chaim A., Gorman, Jason, Moore, Penny L., Bhiman, Jinal N., DeKosky, Brandon J., Ernandes, Michael J., Georgiev, Ivelin S., Kim, Helen J., Pancera, Marie, Staupe, Ryan P., Altae-Tran, Han R., Bailer, Robert T., Crooks, Ema T., Cupo, Albert, Druz, Aliaksandr, Garrett, Nigel J., Hoi, Kam H., Kong, Rui, Louder, Mark K., Longo, Nancy S., McKee, Krisha, Nonyane, Molati, O’Dell, Sijy, Roark, Ryan S., Rudicell, Rebecca S., Schmidt, Stephen D., Sheward, Daniel J., Soto, Cinque, Wibmer, Constantinos Kurt, Yang, Yongping, Zhang, Zhenhai, Mullikin, James C., Binley, James M., Sanders, Rogier W., Wilson, Ian A., Moore, John P., Ward, Andrew B., Georgiou, George, Williamson, Carolyn, Abdool Karim, Salim S., Morris, Lynn, Kwong, Peter D., Shapiro, Lawrence, and Mascola, John R.

Published
2014
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43. Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial

Author

Mayer, Kenneth H., Seaton, Kelly E., Huang, Yunda, Grunenberg, Nicole, Isaacs, Abby, Allen, Mary, Ledgerwood, Julie E., Frank, Ian, Sobieszczyk, Magdalena E., Baden, Lindsey R., Rodriguez, Benigno, Van Tieu, Hong, Tomaras, Georgia D., Deal, Aaron, Goodman, Derrick, Bailer, Robert T., Ferrari, Guido, Jensen, Ryan, Hural, John, Graham, Barney S., Mascola, John R., Corey, Lawrence, and Montefiori, David C.

Subjects
AIDS (Disease) -- Research, AIDS research, Monoclonal antibodies -- Testing, HIV infection -- Care and treatment, Biological sciences
Abstract

Background VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. Methods and findings HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18-50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 [mu]g/ml (95% CI: 1,033, 1,340) and 420 [mu]g/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 [mu]g/ml (95% CI: 10, 27) and 6 [mu]g/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration [IC50] > 5 [mu]g/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits. Conclusions VRC01 administered as either an IV infusion (10-40 mg/kg) given monthly or bimonthly, or as an SC injection (5 mg/kg) every 2 weeks, was found to be safe and well tolerated. In addition to maintaining drug concentrations consistent with neutralization of the majority of tested HIV strains, VRC01 concentrations from participants' sera were found to avidly capture HIV virions and to mediate antibody-dependent cellular phagocytosis, suggesting a range of anti-HIV immunological activities, warranting further clinical trials. Trial registration Clinical Trials Registration: NCT02165267, Author(s): Kenneth H. Mayer 1,*, Kelly E. Seaton 2, Yunda Huang 3, Nicole Grunenberg 3, Abby Isaacs 3, Mary Allen 4, Julie E. Ledgerwood 5, Ian Frank 6, Magdalena E. [...]

Published
2017
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44. Safety and immunogenicity of a gag-pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1-seronegative subjects

Author

Tavel, Jorge A., Martin, Julie E., Kelly, Grace G., Enama, Mary E., Shen, Jean M., Gomez, Phillip L., Andrews, Charla A., Koup, Richard A., Bailer, Robert T., Stein, Judy A., Roederer, Mario, Nabel, Gary J., and Graham, Barney S.

Subjects
DNA vaccines -- Dosage and administration, HIV infection -- Care and treatment, Hypodermic jet injectors -- Usage, Health
Abstract

The safety and immunogenicity of a candidate HIV DNA vaccine administered by using a needle-free device is evaluated. The results have shown that the HIV DNA vaccine is safe and well tolerated and it has led to the development of a 4-plasmid multiclade HIV DNA Vaccine Research Center vaccine candidate in which envelope genes expressing Env from clades A, B, and C and Nef gene from clade B is added.

Published
2007

48. A West Nile virus dna vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial

Author

Martin, Julie E., Pierson, Theodore C., Hubka, Sarah, Rucker, Steve, Gordon, Ingelise J., Enama, Mary E., Andrews, Charla A., Xu, Qing, Davis, Brent S., Nason, Martha C., Fay, Michael P., Koup, Richard A., Roederer, Mario, Bailer, Robert T., Gomez, Phillip L., Mascola, John R., Chang, Gwong-Jen J., Nabel, Gary J., and Graham, Barney S.

Subjects
West Nile virus -- Physiological aspects, West Nile virus -- Research, DNA vaccines -- Dosage and administration, DNA vaccines -- Physiological aspects, DNA vaccines -- Research, Human immunogenetics -- Research, Clinical trials -- Reports, Health
Published
2007

49. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine

Author

Graham, Barney S., Koup, Richard A., Roederer, Mario, Bailer, Robert T., Enama, Mary E., Moodie, Zoe, Martin, Julie E., McCluskey, Margaret M., Chakrabarti, Bimal K., Lamoreaux, Laurie, Andrews, Charla A., Gomez, Phillip L., Mascola, John R., and Nabel, Gary J.

Subjects
AIDS vaccines -- Research, Immunogenetics -- Research, Health
Published
2006

50. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector

Author

Catanzaro, Andrew T., Koup, Richard A., Roederer, Mario, Bailer, Robert T., Enama, Mary E., Moodie, Zoe, Gu, Lin, Martin, Julie E., Novik, Laura, Chakrabarti, Bimal K., Butman, Bryan T., Gall, Jason G.D., King, C. Richter, Andrews, Charla A., Sheets, Rebecca, Gomez, Phillip L., Mascola, John R., Nabel, Gary J., and Graham, Barney S.

Subjects
AIDS vaccines -- Dosage and administration, AIDS vaccines -- Research, Adenoviruses, Human -- Research, Health
Published
2006

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