1,536 results on '"Michael, Nelson L"'
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2. Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG
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Wieczorek, Lindsay, Chang, David, Sanders-Buell, Eric, Zemil, Michelle, Martinez, Elizabeth, Schoen, Jesse, Chenine, Agnes-Laurence, Molnar, Sebastian, Barrows, Brittani, Poltavee, Kultida, Charurat, Man E., Abimiku, Alash’le, Blattner, William, Iroezindu, Michael, Kokogho, Afoke, Michael, Nelson L., Crowell, Trevor A., Ake, Julie A., Tovanabutra, Sodsai, and Polonis, Victoria R.
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- 2024
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3. Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy
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Julg, Boris, Stephenson, Kathryn E., Tomaka, Frank, Walsh, Stephen R., Sabrina Tan, C., Lavreys, Ludo, Sarnecki, Michal, Ansel, Jessica L., Kanjilal, Diane G., Jaegle, Kate, Speidel, Tessa, Nkolola, Joseph P., Borducchi, Erica N., Braams, Esmee, Pattacini, Laura, Burgess, Eleanor, Ilan, Shlomi, Bartsch, Yannic, Yanosick, Katherine E., Seaman, Michael S., Stieh, Daniel J., van Duijn, Janine, Willems, Wouter, Robb, Merlin L., Michael, Nelson L., Walker, Bruce D., Pau, Maria Grazia, Schuitemaker, Hanneke, and Barouch, Dan H.
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- 2024
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4. Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques
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Sankhala, Rajeshwer S., Lal, Kerri G., Jensen, Jaime L., Dussupt, Vincent, Mendez-Rivera, Letzibeth, Bai, Hongjun, Wieczorek, Lindsay, Mayer, Sandra V., Zemil, Michelle, Wagner, Danielle A., Townsley, Samantha M., Hajduczki, Agnes, Chang, William C., Chen, Wei-Hung, Donofrio, Gina C., Jian, Ningbo, King, Hannah A. D., Lorang, Cynthia G., Martinez, Elizabeth J., Rees, Phyllis A., Peterson, Caroline E., Schmidt, Fabian, Hart, Tricia J., Duso, Debra K., Kummer, Lawrence W., Casey, Sean P., Williams, Jazmean K., Kannan, Shruthi, Slike, Bonnie M., Smith, Lauren, Swafford, Isabella, Thomas, Paul V., Tran, Ursula, Currier, Jeffrey R., Bolton, Diane L., Davidson, Edgar, Doranz, Benjamin J., Hatziioannou, Theodora, Bieniasz, Paul D., Paquin-Proulx, Dominic, Reiley, William W., Rolland, Morgane, Sullivan, Nancy J., Vasan, Sandhya, Collins, Natalie D., Modjarrad, Kayvon, Gromowski, Gregory D., Polonis, Victoria R., Michael, Nelson L., Krebs, Shelly J., and Joyce, M. Gordon
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- 2024
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5. SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity
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Martinez, Elizabeth J., Chang, William C., Chen, Wei-Hung, Hajduczki, Agnes, Thomas, Paul V., Jensen, Jaime L., Choe, Misook, Sankhala, Rajeshwer S., Peterson, Caroline E., Rees, Phyllis A., Kimner, Jordan, Soman, Sandrine, Kuklis, Caitlin, Mendez-Rivera, Letzibeth, Dussupt, Vincent, King, Jocelyn, Corbett, Courtney, Mayer, Sandra V., Fernandes, Aldon, Murzello, Kripa, Cookenham, Tres, Hvizdos, Janine, Kummer, Larry, Hart, Tricia, Lanzer, Kathleen, Gambacurta, Julian, Reagan, Matthew, Duso, Debbie, Vasan, Sandhya, Collins, Natalie D., Michael, Nelson L., Krebs, Shelly J., Gromowski, Gregory D., Modjarrad, Kayvon, Kaundinya, John, and Joyce, M. Gordon
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- 2024
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6. Clinical, molecular, and drug resistance epidemiology of HIV in Jordan, 2019-2021: A national study
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Bakri, Faris G., Mukattash, Heyam H., Esmeiran, Hiam, Schluck, Glenna, Storme, Casey K., Broach, Erica, Mebrahtu, Tsedal, Alhawarat, Mohammad, Valencia-Ruiz, Anais, M'Hamdi, Oussama, Malia, Jennifer A., Hassen, Zebiba, Shafei, Mah'd M.S., Alkhatib, Ala Y., Gazo, Mahmoud, Jaradat, Saied A., Gomez, Yessenia, McGeehon, Samantha, McCauley, Melanie D., Moreland, Sarah C., Darden, Janice M., Amare, Mihret, Crowell, Trevor A., Vasan, Sandhya, Michael, Nelson L., Ake, Julie A., Modjarrad, Kayvon, Scott, Paul T., Peel, Sheila A., and Hakre, Shilpa
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- 2024
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7. SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial
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Gebrehana, Beza, Greenleaf, Melissa E, Hamer, Melinda J, Jansen, Nathan K, Jing, Xiaotang, Kagai, Jael, Kourbanova, Kamila, Koren, Michael A, Martin, Monica L, Wuertz, Kathryn McGuckin, Regules, Jason A, Sanborn, Aaron D, Wallace, David, Zhu, Lei, Gromowski, Gregory D, Corbitt, Courtney, Darden, Janice M, Dussupt, Vincent, Golub, Emily S, Headley, Jarrett A, Jarral, Umair M, King, Jocelyn, Krebs, Shelly J, Lay, Jenny, Lilly, Regina, Lynch, Jennifer, Martinez, Elizabeth J, Mayer, Sandra V, McGeehon, Samantha, Lee, Hyunna, Schech, Steven, Tadesse, Mekdi, Thomas, Paul V, Romem, Yahel, Zografos, Erifile, Lin, Bob C, Narpala, Sandeep R, Wang, Lingshu, Doria-Rose, Nicole A, Carroll, Robin E, Eaton, Amanda, Badraslioglu, Emily D, Koontz, Jason M, Nwaeze, Ugo E, Dawson, Peter, Noll, Alexander J, Orndahl, Christine M, Bray, Amy, Carrion, Ricardo, Jr., Patterson, Jean, Kulkarni, Viraj, Hallam, Cory, Gonzalez, Olga, Gazi, Michal, Ober Shepherd, Brittany L, Scott, Paul T, Hutter, Jack N, Lee, Christine, McCauley, Melanie D, Guzman, Ivelese, Bryant, Christopher, McGuire, Sarah, Kennedy, Jessie, Chen, Wei-Hung, Hajduczki, Agnes, Mdluli, Thembi, Valencia-Ruiz, Anais, Amare, Mihret F, Matyas, Gary R, Rao, Mangala, Rolland, Morgane, Mascola, John R, De Rosa, Stephen C, McElrath, M Juliana, Montefiori, David C, Serebryannyy, Leonid, McDermott, Adrian B, Peel, Sheila A, Collins, Natalie D, Joyce, M Gordon, Robb, Merlin L, Michael, Nelson L, Vasan, Sandhya, and Modjarrad, Kayvon
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- 2024
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8. SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies
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Shrivastava, Shikha, Carmen, Joshua M., Lu, Zhongyan, Basu, Shraddha, Sankhala, Rajeshwer S., Chen, Wei-Hung, Nguyen, Phuong, Chang, William C., King, Jocelyn, Corbitt, Courtney, Mayer, Sandra, Bolton, Jessica S., Anderson, Alexander, Swafford, Isabella, Terriquez, Guillermo D., Trinh, Hung V., Kim, Jiae, Jobe, Ousman, Paquin-Proulx, Dominic, Matyas, Gary, R., Gromowski, Gregory D., Currier, Jeffrey R., Bergmann-Leitner, Elke, Modjarrad, Kayvon, Michael, Nelson L., Joyce, M. Gordon, Malloy, Allison M. W., and Rao, Mangala
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- 2023
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9. Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain
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Sankhala, Rajeshwer S., Dussupt, Vincent, Chen, Wei-Hung, Bai, Hongjun, Martinez, Elizabeth J., Jensen, Jaime L., Rees, Phyllis A., Hajduczki, Agnes, Chang, William C., Choe, Misook, Yan, Lianying, Sterling, Spencer L., Swafford, Isabella, Kuklis, Caitlin, Soman, Sandrine, King, Jocelyn, Corbitt, Courtney, Zemil, Michelle, Peterson, Caroline E., Mendez-Rivera, Letzibeth, Townsley, Samantha M., Donofrio, Gina C., Lal, Kerri G., Tran, Ursula, Green, Ethan C., Smith, Clayton, de Val, Natalia, Laing, Eric D., Broder, Christopher C., Currier, Jeffrey R., Gromowski, Gregory D., Wieczorek, Lindsay, Rolland, Morgane, Paquin-Proulx, Dominic, van Dyk, Dewald, Britton, Zachary, Rajan, Saravanan, Loo, Yueh Ming, McTamney, Patrick M., Esser, Mark T., Polonis, Victoria R., Michael, Nelson L., Krebs, Shelly J., Modjarrad, Kayvon, and Joyce, M. Gordon
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- 2024
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10. Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study
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Marichannegowda, Manukumar Honnayakanahalli, Zemil, Michelle, Wieczorek, Lindsay, Sanders-Buell, Eric, Bose, Meera, O'Sullivan, Anne Marie, King, David, Francisco, Leilani, Diaz-Mendez, Felisa, Setua, Saini, Chomont, Nicolas, Phanuphak, Nittaya, Ananworanich, Jintanat, Hsu, Denise, Vasan, Sandhya, Michael, Nelson L., Eller, Leigh Anne, Tovanabutra, Sodsai, Tagaya, Yutaka, Robb, Merlin L., Polonis, Victoria R., and Song, Hongshuo
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- 2023
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11. Priming with Japanese encephalitis virus or yellow fever virus vaccination led to the recognition of multiple flaviviruses without boosting antibody responses induced by an inactivated Zika virus vaccine
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Li, Yifan, Merbah, Mélanie, Wollen-Roberts, Suzanne, Beckman, Bradley, Mdluli, Thembi, Curtis, Daniel J., Currier, Jeffrey R., Mendez-Rivera, Letzibeth, Dussupt, Vincent, Krebs, Shelly J., De La Barrera, Rafael, Michael, Nelson L., Paquin-Proulx, Dominic, Eller, Michael A., Koren, Michael A., Modjarrad, Kayvon, and Rolland, Morgane
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- 2023
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12. Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial
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Abalos, Karina, Accini, Jose, Aloysia, Naveena, Amuasi, John Humphrey, Ansah, Nana Akosua, Benkeser, David, Berge, Aude, Beyko, Hanna, Bilotkach, Oleksandra, Breuer, Thomas, Bonfanti, Alberto Cadena, Bukusi, Elisabeth, Canter, Richard, Carrillo, Jaime Augusto, Chansinghakul, Danaya, Coux, Florence, Das, Chandan, Das, Santa Kumar, Devlin, Louis, Espinoza, Luis, Fay, Michael, Follmann, Dean, Frago, Carina, Garinga, Agnes, Gilbert, Peter B, Gonzalez, Claudia, Granados, Maria Angelica, Guillery, Lea, Huang, Ying, Hudzina, Kathy, Jain, Manish, Kanodia, Piush, Khandelwal, Nitin, Mutuluuza, Cissy Kityo, Kiweewa, Francis, Kiwanuka, Noah, Kosolsak, Chalit, Kukian, Darshna, Kushwaha, Jitendra Singh, Laot, Thelma, Lopez-Medina, Eduardo, Macareno Arroyo, Hugo, Mandaliya, Kishorchandra, Mamod, Stephanie, Mangarule, Somnath, Martínez, Javier, McClelland, Scott, Menard, Lisa, Mendoza, Sandra, Mohapatra, Satyajit, Moreau, Catherine, Mugo, Nelly, Nduba, Videlis, Noriega, Fernando, Ntege, Patricia Nahirya, Okech, Brenda, Otero, Maria, Ouma, Samuel Gurrion, Oyieko, Janet, Paredes, Mercedes, Pardo, Erwin, Postol, Svitlana, Pekala, David, Peng, Penny, Py, Marie-Laure, Rivas, Enrique, Rivero, Rafael, Rodriguez, Edith, Saleh, Mansoor, Sánchez, Pedro, Sater, Nessryne, Shah, Jinen, Shrestha, Rajeev, Siika, Abraham, Singh, Chandramani, Singh, Veer Bahadur, Tamrakar, Dipesh, Tavares Da-Silva, Fernanda, Otieno Tina, Lucas, Velasquez, Hector, Wabwire, Deo, Wajja, Anne, Zaworski, Elodie, Zhang, Nianxian, Dayan, Gustavo H, Rouphael, Nadine, Walsh, Stephen R, Chen, Aiying, Grunenberg, Nicole, Allen, Mary, Antony, Johannes, Asante, Kwaku Poku, Bhate, Amit Suresh, Beresnev, Tatiana, Bonaparte, Matthew I, Celle, Médéric, Ceregido, Maria Angeles, Corey, Lawrence, Dobrianskyi, Dmytro, Fu, Bo, Grillet, Marie-Helene, Keshtkar-Jahromi, Maryam, Juraska, Michal, Kee, Jia Jin, Kibuuka, Hannah, Koutsoukos, Marguerite, Masotti, Roger, Michael, Nelson L, Neuzil, Kathleen M, Reynales, Humberto, Robb, Merlin L, Villagómez Martínez, Sandra M, Sawe, Fredrick, Schuerman, Lode, Tong, Tina, Treanor, John, Wartel, T Anh, Diazgranados, Carlos A, Chicz, Roman M, Gurunathan, Sanjay, Savarino, Stephen, and Sridhar, Saranya
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- 2023
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13. Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study
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Abalos, Karina, Adams, Michael, Allaw, Mohamed, Aloysia, Naveena, Amuasi, John Humphrey, Ansah, Nana Akosua, Asante, Kwaku Poku, Benkeser, David, Berge, Aude, Breuer, Thomas, Briesemeister, Liz, Broder, Gail, Bonfanti, Alberto Cadena, Calinescu, Cornell, Canter, Richard, Carrillo, Jaime Augusto, Chansinghakul, Danaya, Coux, Florence, Das, Chandan, Davies, Matthew, Devlin, Louis, Fay, Michael, Follmann, Dean, Frago, Carina, Fukase, Hiroyuki, Garinga, Agnes, Gilbert, Peter B., Gonzalez, Claudia, Granados, Maria Angelica, Greiwe, Cathy, Guillery, Lea, Hall, Jessicalee, Henderson, Jeffrey, Huang, Ying, Hudzina, Kathy, Hural, John, Hutchens, Mark, Jain, Manish, Jennings, William, Kanodia, Piush, Kimmel, Murray, Kirby, William, Khandelwal, Nitin, Kopp, James, Kosolsak, Chalit, Kublin, Jim, Kukian, Darshna, Kushwaha, Jitendra Singh, Laot, Thelma, Lopez-Medina, Eduardo, Arroyo, Hugo Macareno, Mamod, Stephanie, Mangarule, Somnath, Martin, Troy, Menard, Lisa, Mendoza, Sandra, Meyer, Robert, Middleton, Randle, Miracle, Jill, Mizuyama, Kazuyuki, Mohapatra, Satyajit, Moreau, Catherine, Murray, Linda, Nagamatsu, Shinya, Newberg, Joseph, Noriega, Fernando, Nugent, Paul, Peake-Andrasik, Michele, Pekala, David, Peng, Penny, Py, Marie-Laure, Ramirez, Shelly, Reddy, Chinthaparthi Prabhakar, Reynolds, Michelle, Rivas, Enrique, Sater, Nessryne, Shah, Jinen, Sher, Lawrence, Sieger, Silva, Singh, Chandramani, Singh, Veer Bahadur, Sirisuphmitr, Nuchra, Starkey, Thomas, Suzuki, Kazuo, Tamrakar, Dipesh, Tangemen, Cayce, Da-Silva, Fernanda Tavares, Taylor, David, Tharenos, Leslie, Wartel, T. Anh, Zaworski, Elodie, Zhang, Nianxian, Dayan, Gustavo H., Rouphael, Nadine, Walsh, Stephen R., Chen, Aiying, Grunenberg, Nicole, Allen, Mary, Antony, Johannes, Bhate, Amit Suresh, Beresnev, Tatiana, Bonaparte, Matthew I., Celle, Médéric, Ceregido, Maria Angeles, Corey, Lawrence, Fu, Bo, Grillet, Marie-Helene, Keshtkar-Jahromi, Maryam, Juraska, Michal, Kee, Jia Jin, Kaali, Seyram, Koutsoukos, Marguerite, Masotti, Roger, Michael, Nelson L., Neuzil, Kathleen M., Reynales, Humberto, Robb, Merlin L., Uchiyama, Akiyoshi, Sawe, Fredrick, Schuerman, Lode, Shrestha, Rajeev, Tong, Tina, Treanor, John, Diazgranados, Carlos A., Chicz, Roman M., Gurunathan, Sanjay, Savarino, Stephen, and Sridhar, Saranya
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- 2023
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14. Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in adults primed with a Japanese encephalitis virus or yellow fever virus vaccine in the USA: a phase 1, randomised, double-blind, placebo-controlled clinical trial
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Koren, Michael A, Lin, Leyi, Eckels, Kenneth H, De La Barrera, Rafael, Dussupt, Vincent, Donofrio, Gina, Sondergaard, Erica L, Mills, Kristin T, Robb, Merlin L, Lee, Christine, Adedeji, Oluwaseun, Keiser, Paul B, Curley, Justin M, Copeland, Nathanial K, Crowell, Trevor A, Hutter, Jack N, Hamer, Melinda J, Valencia-Ruiz, Anais, Darden, Janice, Peel, Sheila, Amare, Mihret F, Mebrahtu, Tsedal, Costanzo, Margaret, Krebs, Shelly J, Gromowski, Gregory D, Jarman, Richard G, Thomas, Stephen J, Michael, Nelson L, and Modjarrad, Kayvon
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- 2023
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15. Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes
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Sankhala, Rajeshwer S., Dussupt, Vincent, Donofrio, Gina, Gromowski, Gregory D., De La Barrera, Rafael A., Larocca, Rafael A., Mendez-Rivera, Letzibeth, Lee, Anna, Choe, Misook, Zaky, Weam, Mantus, Grace, Jensen, Jaime L., Chen, Wei-Hung, Gohain, Neelakshi, Bai, Hongjun, McCracken, Michael K., Mason, Rosemarie D., Leggat, David, Slike, Bonnie M., Tran, Ursula, Jian, Ningbo, Abbink, Peter, Peterson, Rebecca, Mendes, Erica Araujo, Freitas de Oliveira Franca, Rafael, Calvet, Guilherme Amaral, Bispo de Filippis, Ana Maria, McDermott, Adrian, Roederer, Mario, Hernandez, Mayda, Albertus, Amie, Davidson, Edgar, Doranz, Benjamin J., Rolland, Morgane, Robb, Merlin L., Lynch, Rebecca M., Barouch, Dan H., Jarman, Richard G., Thomas, Stephen J., Modjarrad, Kayvon, Michael, Nelson L., Krebs, Shelly J., and Joyce, M. Gordon
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- 2023
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16. Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study
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de Bruyn, Guy, Wang, Joyce, Purvis, Annie, Ruiz, Martin Sanchez, Adhikarla, Haritha, Alvi, Saad, Bonaparte, Matthew I., Brune, Daniel, Bueso, Agustin, Canter, Richard M., Ceregido, Maria Angeles, Deshmukh, Sachin, Diemert, David, Finn, Adam, Forrat, Remi, Fu, Bo, Gallais, Julie, Griffin, Paul, Grillet, Marie-Helene, Haney, Owen, Henderson, Jeffrey A., Koutsoukos, Marguerite, Launay, Odile, Torres, Federico Martinon, Masotti, Roger, Michael, Nelson L., Park, Juliana, Rivera-Medina, Doris Maribel, Romanyak, Natalya, Rook, Chris, Schuerman, Lode, Sher, Lawrence D., Tavares-Da-Silva, Fernanda, Whittington, Ashley, Chicz, Roman M., Gurunathan, Sanjay, Savarino, Stephen, Sridhar, Saranya, Mohammed, Allaw, Valérie, Babin, Jennifer, Babyak, Ben-Ghezala, Ines, Breuer, Thomas, Breymeier, Corinne, Conrad, Anne, Holmqvist, Ciarrah, Costa-Araujo, Cristiana, Coux, Florence, Dellanno, Christine, Dussol, Bertrand, Essink, Brandon, Garrido, Jesús, Girodet, Pierre-Olivier, Gonzalez, Claudia, Grosbois, Marie-Ange, Hammond, Justin, He, Chelsea, Homlqvist, Ciarrah, Hudzina, Kathy, Hutchens, Mark, Jackson Booth, Peta-Gay, Joaquin, Arnel, Kandasamy, Rama, Kasztejna, Jennifer, Keefer, Michael, Kimmel, Murray, Kresge, Matthew, Laine, Fabrice, Lefebvre, Maeva, Lopez, Denise, Lourdes, Malaborbor Perpetua, Maakaroun-Vermesse, Zoha, Malishchak, Caitlin, Menard, Lisa, Mendoza, Sandra, Moore, Patrick, Mulamalla, Mounika, Mulholland, Patrick, Nicolas, Jean-Francois, Ogbuagu, Onyema, Ortiz, Juan, Perroud, Ana Paula, Peyton, Gina, Purvis, Ya-Fen, Raabe, Vanessa, Rivas, Enrique, Rouphael, Nadine, Roy, Beatrice, Sagot, Lola, Sater, Nessryne, Schwartz, Howard, Severance, Randall, Shi, Jiayuan, Sobieszczyk, Magdalena, Stevens, Charlene, Thuy, Tran Phuong, Toma, Ramy, Tong, Tina, Tourneux, Sophie, Treanor, John, Turet, Núria, Froget, Rachel, Walsh, Stephen, White, Judith, del Campo Perez, Victor, Perez Breva, Lina, Rojo Conejo, Pablo, Ruiz Antoraz, Maria Belen, Chin, Toong, Fribbens, Charlotte, Phillipson, Adrian, Kaminski, Rachel, Emmett, Stevan, Hebert, Corey, Birch, Thomas, Roberson, Russell, Zacher, Jeffrey, Gelu-Maury, Sophie, Loryne, Loron, and Davis, Yvonne
- Published
- 2023
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17. Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.
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Lal, Kerri G, Kim, Dohoon, Costanzo, Margaret C, Creegan, Matthew, Leeansyah, Edwin, Dias, Joana, Paquin-Proulx, Dominic, Eller, Leigh Anne, Schuetz, Alexandra, Phuang-Ngern, Yuwadee, Krebs, Shelly J, Slike, Bonnie M, Kibuuka, Hannah, Maganga, Lucas, Nitayaphan, Sorachai, Kosgei, Josphat, Sacdalan, Carlo, Ananworanich, Jintanat, Bolton, Diane L, Michael, Nelson L, Shacklett, Barbara L, Robb, Merlin L, Eller, Michael A, and Sandberg, Johan K
- Abstract
Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality.
- Published
- 2020
18. Preferential and persistent impact of acute HIV-1 infection on CD4⁺ iNKT cells in colonic mucosa
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RV217, RV254/SEARCH010, RV304/SEARCH013 StudyGroup, Paquin-Proulx, Dominic, Lal, Kerri G., Phuang-Ngern, Yuwadee, Creegan, Matthew, Tokarev, Andrey, Suhkumvittay, Suchada, Alrubayyi, Aljawharah, Kroon, Eugène, Pinyakorn, Suteeraporn, Slike, Bonnie M., Bolton, Diane L., Krebs, Shelly J., Eller, Leigh Anne, Sajjaweerawan, Chayada, Pagliuzza, Amélie, Chomont, Nicolas, Rerknimitr, Rungsun, Chomchey, Nitiya, Phanuphak, Nittaya, de Souza, Mark S., Michael, Nelson L., Robb, Merlin L., Ananworanich, Jintanat, Sandberg, Johan K., Eller, Michael A., and Schuetz, Alexandra
- Published
- 2021
19. Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques
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Yu, Jingyou, Thomas, Paul V., Sciacca, Michaela, Wu, Cindy, Liu, Jinyan, He, Xuan, Miller, Jessica, Hachmann, Nicole P., Surve, Nehalee, McMahan, Katherine, Jacob-Dolan, Catherine, Powers, Olivia, Hall, Kevin, Barrett, Julia, Hope, David, Mazurek, Camille R., Murdza, Tetyana, Chang, William C., Golub, Emily, Rees, Phyllis A., Peterson, Caroline E., Hajduczki, Agnes, Chen, Wei-Hung, Martinez, Elizabeth J., Hussin, Elizabeth, Lange, Camille, Gong, Hua, Matyas, Gary R., Rao, Mangala, Suthar, Mehul, Boursiquot, Mona, Cook, Anthony, Pessaint, Laurent, Lewis, Mark G., Andersen, Hanne, Bolton, Diane L., Michael, Nelson L., Joyce, M. Gordon, Modjarrad, Kayvon, and Barouch, Dan H.
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- 2023
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20. Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques
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King, Hannah A. D., Joyce, M. Gordon, Lakhal-Naouar, Ines, Ahmed, Aslaa, Cincotta, Camila Macedo, Subra, Caroline, Peachman, Kristina K., Hack, Holly R., Chen, Rita E., Thomas, Paul V., Chen, Wei-Hung, Sankhala, Rajeshwer S., Hajduczki, Agnes, Martinez, Elizabeth J., Peterson, Caroline E., Chang, William C., Choe, Misook, Smith, Clayton, Headley, Jarrett A., Elyard, Hanne A., Cook, Anthony, Anderson, Alexander, Wuertz, Kathryn McGuckin, Dong, Ming, Swafford, Isabella, Case, James B., Currier, Jeffrey R., Lal, Kerri G., Amare, Mihret F., Dussupt, Vincent, Molnar, Sebastian, Daye, Sharon P., Zeng, Xiankun, Barkei, Erica K., Alfson, Kendra, Staples, Hilary M., Carrion, Ricardo, Krebs, Shelly J., Paquin-Proulx, Dominic, Karasavvas, Nicos, Polonis, Victoria R., Jagodzinski, Linda L., Vasan, Sandhya, Scott, Paul T., Huang, Yaoxing, Nair, Manoj S., Ho, David D., de Val, Natalia, Diamond, Michael S., Lewisi, Mark G., Rao, Mangala, Matyas, Gary R., Gromowski, Gregory D., Peel, Sheila A., Michael, Nelson L., Modjarrad, Kayvon, and Bolton, Diane L.
- Published
- 2021
21. SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial
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Ober Shepherd, Brittany L, primary, Scott, Paul T, additional, Hutter, Jack N, additional, Lee, Christine, additional, McCauley, Melanie D, additional, Guzman, Ivelese, additional, Bryant, Christopher, additional, McGuire, Sarah, additional, Kennedy, Jessie, additional, Chen, Wei-Hung, additional, Hajduczki, Agnes, additional, Mdluli, Thembi, additional, Valencia-Ruiz, Anais, additional, Amare, Mihret F, additional, Matyas, Gary R, additional, Rao, Mangala, additional, Rolland, Morgane, additional, Mascola, John R, additional, De Rosa, Stephen C, additional, McElrath, M Juliana, additional, Montefiori, David C, additional, Serebryannyy, Leonid, additional, McDermott, Adrian B, additional, Peel, Sheila A, additional, Collins, Natalie D, additional, Joyce, M Gordon, additional, Robb, Merlin L, additional, Michael, Nelson L, additional, Vasan, Sandhya, additional, Modjarrad, Kayvon, additional, Gebrehana, Beza, additional, Greenleaf, Melissa E, additional, Hamer, Melinda J, additional, Jansen, Nathan K, additional, Jing, Xiaotang, additional, Kagai, Jael, additional, Kourbanova, Kamila, additional, Koren, Michael A, additional, Martin, Monica L, additional, Wuertz, Kathryn McGuckin, additional, Regules, Jason A, additional, Sanborn, Aaron D, additional, Wallace, David, additional, Zhu, Lei, additional, Gromowski, Gregory D, additional, Corbitt, Courtney, additional, Darden, Janice M, additional, Dussupt, Vincent, additional, Golub, Emily S, additional, Headley, Jarrett A, additional, Jarral, Umair M, additional, King, Jocelyn, additional, Krebs, Shelly J, additional, Lay, Jenny, additional, Lilly, Regina, additional, Lynch, Jennifer, additional, Martinez, Elizabeth J, additional, Mayer, Sandra V, additional, McGeehon, Samantha, additional, Lee, Hyunna, additional, Schech, Steven, additional, Tadesse, Mekdi, additional, Thomas, Paul V, additional, Romem, Yahel, additional, Zografos, Erifile, additional, Lin, Bob C, additional, Narpala, Sandeep R, additional, Wang, Lingshu, additional, Doria-Rose, Nicole A, additional, Carroll, Robin E, additional, Eaton, Amanda, additional, Badraslioglu, Emily D, additional, Koontz, Jason M, additional, Nwaeze, Ugo E, additional, Dawson, Peter, additional, Noll, Alexander J, additional, Orndahl, Christine M, additional, Bray, Amy, additional, Carrion, Ricardo, additional, Patterson, Jean, additional, Kulkarni, Viraj, additional, Hallam, Cory, additional, Gonzalez, Olga, additional, and Gazi, Michal, additional
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- 2024
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22. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting
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Julg, Boris, Dee, Lynda, Ananworanich, Jintanat, Barouch, Dan H, Bar, Katharine, Caskey, Marina, Colby, Donn J, Dawson, Liza, Dong, Krista L, Dubé, Karine, Eron, Joseph, Frater, John, Gandhi, Rajesh T, Geleziunas, Romas, Goulder, Philip, Hanna, George J, Jefferys, Richard, Johnston, Rowena, Kuritzkes, Daniel, Li, Jonathan Z, Likhitwonnawut, Udom, van Lunzen, Jan, Martinez-Picado, Javier, Miller, Veronica, Montaner, Luis J, Nixon, Douglas F, Palm, David, Pantaleo, Giuseppe, Peay, Holly, Persaud, Deborah, Salzwedel, Jessica, Salzwedel, Karl, Schacker, Timothy, Sheikh, Virginia, Søgaard, Ole S, Spudich, Serena, Stephenson, Kathryn, Sugarman, Jeremy, Taylor, Jeff, Tebas, Pablo, Tiemessen, Caroline T, Tressler, Randall, Weiss, Carol D, Zheng, Lu, Robb, Merlin L, Michael, Nelson L, Mellors, John W, Deeks, Steven G, and Walker, Bruce D
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Infection ,Anti-Retroviral Agents ,HIV Infections ,Humans ,Sustained Virologic Response ,Viral Load ,Withholding Treatment ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.
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- 2019
23. Dissecting drivers of immune activation in chronic HIV-1 infection
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Streeck, Hendrik, Maestri, Alvino, Habermann, Daniel, Crowell, Trevor A., Esber, Allahna L., Son, Gowoon, Eller, Leigh Anne, Eller, Michael A., Parikh, Ajay P., Horn, Peter A., Maganga, Lucas, Bahemana, Emmanuel, Adamu, Yakubu, Kiweewa, Francis, Maswai, Jonah, Owuoth, John, Robb, Merlin L., Michael, Nelson L., Polyak, Christina S., Hoffmann, Daniel, and Ake, Julie A.
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- 2022
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24. Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study
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Sridhar, Saranya, Joaquin, Arnel, Bonaparte, Matthew I, Bueso, Agustin, Chabanon, Anne-Laure, Chen, Aiying, Chicz, Roman M, Diemert, David, Essink, Brandon J, Fu, Bo, Grunenberg, Nicole A, Janosczyk, Helene, Keefer, Michael C, Rivera M, Doris M, Meng, Ya, Michael, Nelson L, Munsiff, Sonal S, Ogbuagu, Onyema, Raabe, Vanessa N, Severance, Randall, Rivas, Enrique, Romanyak, Natalya, Rouphael, Nadine G, Schuerman, Lode, Sher, Lawrence D, Walsh, Stephen R, White, Judith, von Barbier, Dalia, de Bruyn, Guy, Canter, Richard, Grillet, Marie-Helene, Keshtkar-Jahromi, Maryam, Koutsoukos, Marguerite, Lopez, Denise, Masotti, Roger, Mendoza, Sandra, Moreau, Catherine, Ceregido, Maria Angeles, Ramirez, Shelly, Said, Ansoyta, Tavares-Da-Silva, Fernanda, Shi, Jiayuan, Tong, Tina, Treanor, John, Diazgranados, Carlos A, and Savarino, Stephen
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- 2022
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25. Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques
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Ventura, John D., Nkolola, Joseph P., Chandrashekar, Abishek, Borducchi, Erica N., Liu, Jinyan, Mercado, Noe B., Hope, David L., Giffin, Victoria M., McMahan, Katherine, Geleziunas, Romas, Murry, Jeffrey P., Yang, Yunling, Lewis, Mark G., Pau, Maria G., Wegmann, Frank, Schuitemaker, Hanneke, Fray, Emily J., Kumar, Mithra R., Siliciano, Janet D., Siliciano, Robert F., Robb, Merlin L., Michael, Nelson L., and Barouch, Dan H.
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- 2022
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26. Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques
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Walker-Sperling, Victoria E. K., Mercado, Noe B., Chandrashekar, Abishek, Borducchi, Erica N., Liu, Jinyan, Nkolola, Joseph P., Lewis, Mark, Murry, Jeffrey P., Yang, Yunling, Geleziunas, Romas, Robb, Merlin L., Michael, Nelson L., Pau, Maria G., Wegmann, Frank, Schuitemaker, Hanneke, Fray, Emily J., Kumar, Mithra R., Siliciano, Janet D., Siliciano, Robert F., and Barouch, Dan H.
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- 2022
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27. Neurocognitive impact of Zika virus infection in adult rhesus macaques
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Hsu, Denise C., Chumpolkulwong, Kesara, Corley, Michael J., Hunsawong, Taweewun, Inthawong, Dutsadee, Schuetz, Alexandra, Imerbsin, Rawiwan, Silsorn, Decha, Nadee, Panupat, Sopanaporn, Jumpol, Phuang-Ngern, Yuwadee, Klungthong, Chonticha, Reed, Matthew, Fernandez, Stefan, Ndhlovu, Lishomwa C., Paul, Robert, Lugo-Roman, Luis, Michael, Nelson L., Modjarrad, Kayvon, and Vasan, Sandhya
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- 2022
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28. Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand
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Thomas, Rasmi, Chansinghakul, Danaya, Limkittikul, Kriengsak, Gilbert, Peter B., Hattasingh, Weerawan, Moodie, Zoe, Shangguan, Shida, Frago, Carina, Dulyachai, Wut, Li, Shuying Sue, Jarman, Richard G., Geretz, Aviva, Bouckenooghe, Alain, Sabchareon, Arunee, Juraska, Michal, Ehrenberg, Philip, Michael, Nelson L., Bailleux, Fabrice, Bryant, Chris, and Gurunathan, Sanjay
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- 2022
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29. HLA tapasin independence : broader peptide repertoire and HIV control
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Bashirova, Arman A., Viard, Mathias, Naranbhai, Vivek, Grifoni, Alba, Garcia-Beltran, Wilfredo, Akdag, Marjan, Yuki, Yuko, Gao, Xiaojiang, O’hUigin, Colm, Raghavan, Malini, Wolinsky, Steven, Bream, Jay H., Duggal, Priya, Martinson, Jeremy, Michael, Nelson L., Kirk, Gregory D., Buchbinder, Susan P., Haas, David, Goedert, James J., Deeks, Steven G., Fellay, Jacques, Walker, Bruce, Goulder, Philip, Cresswell, Peter, Elliott, Tim, Sette, Alessandro, Carlson, Jonathan, and Carrington, Mary
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- 2020
30. Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations
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Dussupt, Vincent, Sankhala, Rajeshwer S., Mendez-Rivera, Letzibeth, Townsley, Samantha M., Schmidt, Fabian, Wieczorek, Lindsay, Lal, Kerri G., Donofrio, Gina C., Tran, Ursula, Jackson, Nathaniel D., Zaky, Weam I., Zemil, Michelle, Tritsch, Sarah R., Chen, Wei-Hung, Martinez, Elizabeth J., Ahmed, Aslaa, Choe, Misook, Chang, William C., Hajduczki, Agnes, Jian, Ningbo, Peterson, Caroline E., Rees, Phyllis A., Rutkowska, Magdalena, Slike, Bonnie M., Selverian, Christopher N., Swafford, Isabella, Teng, I-Ting, Thomas, Paul V., Zhou, Tongqing, Smith, Clayton J., Currier, Jeffrey R., Kwong, Peter D., Rolland, Morgane, Davidson, Edgar, Doranz, Benjamin J., Mores, Christopher N., Hatziioannou, Theodora, Reiley, William W., Bieniasz, Paul D., Paquin-Proulx, Dominic, Gromowski, Gregory D., Polonis, Victoria R., Michael, Nelson L., Modjarrad, Kayvon, Joyce, M. Gordon, and Krebs, Shelly J.
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- 2021
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31. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells
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Ramsuran, Veron, Naranbhai, Vivek, Horowitz, Amir, Qi, Ying, Martin, Maureen P, Yuki, Yuko, Gao, Xiaojiang, Walker-Sperling, Victoria, Del Prete, Gregory Q, Schneider, Douglas K, Lifson, Jeffrey D, Fellay, Jacques, Deeks, Steven G, Martin, Jeffrey N, Goedert, James J, Wolinsky, Steven M, Michael, Nelson L, Kirk, Gregory D, Buchbinder, Susan, Haas, David, Ndung’u, Thumbi, Goulder, Philip, Parham, Peter, Walker, Bruce D, Carlson, Jonathan M, and Carrington, Mary
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,HIV/AIDS ,Women's Health ,Infectious Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Infection ,Alleles ,CD4 Lymphocyte Count ,Cohort Studies ,HIV ,HIV Infections ,HLA Antigens ,Humans ,Killer Cells ,Natural ,Ligands ,NK Cell Lectin-Like Receptor Subfamily C ,Protein Sorting Signals ,Viremia ,General Science & Technology - Abstract
The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.
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- 2018
32. Differential Inhibitory Receptor Expression on T Cells Delineates Functional Capacities in Chronic Viral Infection
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Teigler, Jeffrey E, Zelinskyy, Gennadiy, Eller, Michael A, Bolton, Diane L, Marovich, Mary, Gordon, Alexander D, Alrubayyi, Aljawharah, Alter, Galit, Robb, Merlin L, Martin, Jeffrey N, Deeks, Steven G, Michael, Nelson L, Dittmer, Ulf, and Streeck, Hendrik
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Emerging Infectious Diseases ,HIV/AIDS ,Sexually Transmitted Infections ,Immunotherapy ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Animals ,Antibodies ,CD4-Positive T-Lymphocytes ,CTLA-4 Antigen ,Costimulatory and Inhibitory T-Cell Receptors ,Cytokines ,Enterotoxins ,Friend murine leukemia virus ,Gene Expression ,HIV Infections ,Humans ,Interferon-gamma ,Mice ,Programmed Cell Death 1 Receptor ,Retroviridae Infections ,Tumor Necrosis Factor-alpha ,CD4 T cells ,CTLA-4 ,HIV ,PD-1 ,inhibitory receptors ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
Inhibitory receptors have been extensively described for their importance in regulating immune responses in chronic infections and cancers. Blocking the function of inhibitory receptors such as PD-1, CTLA-4, 2B4, Tim-3, and LAG-3 has shown promise for augmenting CD8 T cell activity and boosting pathogen-specific immunity. However, the prevalence of inhibitory receptors on CD4 T cells and their relative influence on CD4 T cell functionality in chronic HIV infection remains poorly described. We therefore determined and compared inhibitory receptor expression patterns of 2B4, CTLA-4, LAG-3, PD-1, and Tim-3 on virus-specific CD4 and CD8 T cells in relation to their functional T cell profile. In chronic HIV infection, inhibitory receptor distribution differed markedly between cytokine-producing T cell subsets with, gamma interferon (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-producing cells displaying the highest and lowest prevalence of inhibitory receptors, respectively. Blockade of inhibitory receptors differentially affected cytokine production by cells in response to staphylococcal enterotoxin B stimulation. CTLA-4 blockade increased IFN-γ and CD40L production, while PD-1 blockade strongly augmented IFN-γ, interleukin-2 (IL-2), and TNF-α production. In a Friend retrovirus infection model, CTLA-4 blockade in particular was able to improve control of viral replication. Together, these results show that inhibitory receptor distribution on HIV-specific CD4 T cells varies markedly with respect to the functional subset of CD4 T cells being analyzed. Furthermore, the differential effects of receptor blockade suggest novel methods of immune response modulation, which could be important in the context of HIV vaccination or therapeutic strategies.IMPORTANCE Inhibitory receptors are important for limiting damage by the immune system during acute infections. In chronic infections, however, their expression limits immune system responsiveness. Studies have shown that blocking inhibitory receptors augments CD8 T cell functionality in HIV infection, but their influence on CD4 T cells remains unclear. We assessed the expression of inhibitory receptors on HIV-specific CD4 T cells and their relationship with T cell functionality. We uncovered differences in inhibitory receptor expression depending on the CD4 T cell function. We also found differences in functionality of CD4 T cells following blocking of different inhibitory receptors, and we confirmed our results in a Friend virus retroviral model of infection in mice. Our results show that inhibitory receptor expression on CD4 T cells is linked to CD4 T cell functionality and could be sculpted by blockade of specific inhibitory receptors. These data reveal exciting possibilities for the development of novel treatments and immunotherapeutics.
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- 2017
33. A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants
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Dearlove, Bethany, Lewitus, Eric, Bai, Hongjun, Li, Yifan, Reeves, Daniel B., Joyce, M. Gordon, Scott, Paul T., Amare, Mihret F., Vasan, Sandhya, Michael, Nelson L., Modjarrad, Kayvon, and Rolland, Morgane
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- 2020
34. The transcription factor CREB1 is a mechanistic driver of immunogenicity and reduced HIV-1 acquisition following ALVAC vaccination
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Tomalka, Jeffrey Alan, Pelletier, Adam Nicolas, Fourati, Slim, Latif, Muhammad Bilal, Sharma, Ashish, Furr, Kathryn, Carlson, Kevin, Lifton, Michelle, Gonzalez, Ana, Wilkinson, Peter, Franchini, Genoveffa, Parks, Robert, Letvin, Norman, Yates, Nicole, Seaton, Kelly, Tomaras, Georgia, Tartaglia, Jim, Robb, Merlin L., Michael, Nelson L., Koup, Richard, Haynes, Barton, Santra, Sampa, and Sekaly, Rafick Pierre
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- 2021
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35. Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults
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Cohen, Kristen W., Fiore-Gartland, Andrew, Walsh, Stephen R., Yusim, Karina, Frahm, Nicole, Elizaga, Marnie L., Maenza, Janine, Scott, Hyman, Mayer, Kenneth H., Goepfert, Paul A., Edupuganti, Srilatha, Pantaleo, Giuseppe, Hutter, Julia, Morris, Daryl E., de Rosa, Stephen C., Geraghty, Daniel E., Robb, Merlin L., Michael, Nelson L., Fischer, Will, Giorgi, Elena E., Malhi, Harmandeep, Pensiero, Michael N., Ferrari, Guido, Tomaras, Georgia D., Montefiori, David C., Gilbert, Peter B., McElrath, M. Juliana, Haynes, Barton F., Korber, Bette T., and Baden, Lindsey R.
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Cellular immunity -- Health aspects ,Immune response -- Health aspects ,DNA vaccines -- Testing ,Antigens -- Health aspects ,AIDS vaccines -- Testing ,HIV infection -- Drug therapy ,Health care industry - Abstract
BACKGROUND. Mosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models. METHODS. This double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara-vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped. RESULTS. Env-specific [CD4.sup.+] T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2-4.2) for mosaic recipients, 1.6 (95% CI, 0.82-2.6) for CON-S recipients, and 1.1 (95% CI, 0.62-1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific [CD4.sup.+] T cell responses. CONCLUSION. Priming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1. TRIAL REGISTRATION. ClinicalTrials.gov NCT02296541. FUNDING. US NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill & Melinda Gates Foundation grant OPP52282., Introduction The tremendous global genetic diversity of HIV-1 poses a formidable challenge in the development of a globally effective HIV-1 vaccine (1, 2). Several vaccine concepts have completed efficacy trials [...]
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- 2023
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36. A tale of four studies: HIV vaccine immunogenicity and efficacy in clinical trials
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Zolla-Pazner, Susan, Michael, Nelson L, and Kim, Jerome H
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- 2021
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37. Immune correlates of protection for dengue: State of the art and research agenda
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Katzelnick, Leah C, Harris, Eva, Baric, Ralph, Coller, Beth-Ann, Coloma, Josefina, Crowe, James E, Cummings, Derek AT, Dean, Hansi, de Silva, Aravinda, Diamond, Michael S, Durbin, Anna, Ferguson, Neil, Gilbert, Peter B, Gordon, Aubree, Gubler, Duane J, Guy, Bruno, Halloran, M Elizabeth, Halstead, Scott, Jackson, Nicholas, Jarman, Richard, Lok, Shee-mei, Michael, Nelson L, Ooi, Eng Eong, Papadopoulos, Athanasios, Plotkin, Stanley, Precioso, Alexander R, Reiner, Robert, Rey, Felix A, Rodríguez-Barraquer, Isabel, Rothman, Alan, Schmidt, Alexander C, Screaton, Gavin, Sette, Alessandro, Simmons, Cameron, St. John, Ashley L, Sun, Wellington, Thomas, Stephen, Torresi, Joseph, Tsang, John S, Vannice, Kirsten, Whitehead, Stephen, Wilder-Smith, Annelies, and Kyu Yoon, In
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Infectious Diseases ,Vector-Borne Diseases ,Rare Diseases ,Vaccine Related ,Biodefense ,Immunization ,Prevention ,Emerging Infectious Diseases ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,Infection ,Good Health and Well Being ,Antibodies ,Neutralizing ,Antibodies ,Viral ,Clinical Trials ,Phase II as Topic ,Clinical Trials ,Phase III as Topic ,Congresses as Topic ,Dengue ,Dengue Vaccines ,Dengue Virus ,Humans ,Severe Dengue ,Dengue virus ,Immune correlates of protection ,Immune correlates of risk ,Natural infection ,Vaccine ,Participants in the Summit on Dengue Immune Correlates of Protection ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology - Abstract
Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely. At the "Summit on Dengue Immune Correlates of Protection", held in Annecy, France, on March 8-9, 2016, dengue experts from diverse fields came together to discuss the current understanding of the immune response to and protection from DENV infection and disease, identify key unanswered questions, discuss data on immune correlates and plans for comparison of results across assays/consortia, and propose a research agenda for investigation of dengue immune correlates, all in the context of both natural infection studies and vaccine trials.
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- 2017
38. Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers
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Buranapraditkun, Supranee, Pissani, Franco, Teigler, Jeffrey E, Schultz, Bruce T, Alter, Galit, Marovich, Mary, Robb, Merlin L, Eller, Michael A, Martin, Jeff, Deeks, Steven, Michael, Nelson L, and Streeck, Hendrik
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Vaccine Related (AIDS) ,Vaccine Related ,Sexually Transmitted Infections ,Immunization ,Infectious Diseases ,Prevention ,HIV/AIDS ,Health Disparities ,Clinical Research ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Adult ,B-Lymphocytes ,CD4-Positive T-Lymphocytes ,Female ,Germinal Center ,HIV Envelope Protein gp120 ,HIV Infections ,HIV Long-Term Survivors ,Humans ,Immunophenotyping ,Interleukins ,Male ,Middle Aged ,Receptors ,CXCR5 ,T-Lymphocytes ,Helper-Inducer ,B cell memory ,CD4 T cells ,IL-21 ,Tfh cells ,elite controllers ,human immunodeficiency virus ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion. Counterintuitively, the factors associated with perturbation of the B cell compartment seem to be favorable for the generation of highly affinity-matured Env-specific antibodies in a minority of HIV-infected individuals. Thus, the impact of HIV antigenemia on B cells and Tfh cell interactions warrants further exploration. We therefore studied immunophenotypes of HIV-specific B cells in individuals with differing levels of viral control using HIV Env gp120 probes and characterized the functionality of matched T cells in peripheral blood. While CXCR5+ CD4+ T cells were significantly diminished in HIV progressors, we found that a small subset of gp120-specific interleukin-21 (IL-21)-secreting CXCR5+ CD4+ T cells were significantly associated with gp120-specific B cell frequencies. In contrast, neither bulk CXCR5+ CD4+ T cells nor other HIV antigen specificities were associated with gp120-specific B cell levels. HIV-specific B cells derived from elite controllers displayed greater amounts of gp120-specific B cells in the resting memory subset, whereas HIV-specific B cells in progressors accumulated in tissue-like and activated memory subsets. Furthermore, CXCR5+ CD4+ T cells from elite controllers showed a stronger ex vivo capacity to induce B cell maturation and immunoglobulin class switching than cells from HIV progressors.IMPORTANCE Dissecting the factors that are involved in B cell maturation and antibody development is important for HIV vaccine design. In this study, we found that HIV Env-specific CXCR5+ CD4+ T cells that secrete interleukin-21 are strongly associated with B cell memory phenotypes and function. Moreover, we found that the immune responses of HIV controllers showed intrinsically better helper activity than those of HIV progressors.
- Published
- 2017
39. Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial
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Stephenson, Kathryn E, Tan, Chen Sabrina, Walsh, Stephen R, Hale, Andrew, Ansel, Jessica L, Kanjilal, Diane G, Jaegle, Kate, Peter, Lauren, Borducchi, Erica N, Nkolola, Joseph P, Makoni, Tatenda, Fogel, Rachel, Bradshaw, Connor, Tyler, Anna, Moseley, Edward, Chandrashekar, Abishek, Yanosick, Katherine E, Seaman, Michael S, Eckels, Kenneth H, De La Barrera, Rafael A, Thompson, Jason, Dawson, Peter, Thomas, Stephen J, Michael, Nelson L, Modjarrad, Kayvon, and Barouch, Dan H
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- 2020
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40. Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial
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Pitisuthitham, Arom, Sabmee, Yupa, Sirisopana, Narongrid, Eamsila, Chirapa, Savaraj, Prapaporn, Labwech, Wanlaya, Teerachia, Siriluck, Chotirosniramit, Nuntisa, Supindham, Taweewat, Pruenglampoo, Boonlure, Sugandhavesa, Patcharaphan, Kosashunhanan, Natthapol, Kaewthip, Oranitcha, Sroysuwan, Piyathida, Jarujareet, Pawinee, Ratto-Kim, Silvia, Molnar, Sebastian, Schoen, Jesse, Churikanont, Nampueng, Getchalarat, Saowanit, Sangnoi, Nongluck, Nuntapinit, Bessara, Phramtong, Anant, Grandin, Pornsuk V., Madnote, Sirinan, Rittiroongrad, Surawach, Kaewboon, Boot, Trichavaroj, Rapee, Puangkaew, Jiraporn, Chantakulkij, Somsak, Rakyat, Phiromrat, Panjapornsuk, Pornchanok, Tragonlugsana, Nipattra, Chuenarom, Weerawan, de Souza, Mark, Ngauy, Viseth, Phanuphak, Nittaya, Chomchey, Nitiya, Saengtawan, Puttachard, Teeratakulpisarn, Nipat, Rerknimitr, Rungsun, Kroon, Eugene, Lee, Carter A., Chinaworapong, Suchada, Pitisuttithum, Punnee, Nitayaphan, Sorachai, Chariyalertsak, Suwat, Kaewkungwal, Jaranit, Dawson, Peter, Dhitavat, Jittima, Phonrat, Benjaluck, Akapirat, Siriwat, Karasavvas, Nicos, Wieczorek, Lindsay, Polonis, Victoria, Eller, Michael A, Pegu, Poonam, Kim, Dohoon, Schuetz, Alexandra, Jongrakthaitae, Surat, Zhou, Yingjun, Sinangil, Faruk, Phogat, Sanjay, Diazgranados, Carlos A, Tartaglia, James, Heger, Elizabeth, Smith, Kirsten, Michael, Nelson L, Excler, Jean-Louis, Robb, Merlin L, Kim, Jerome H, O'Connell, Robert J, and Vasan, Sandhya
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- 2020
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41. Impact of HLA class I functional divergence on HIV control
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Viard, Mathias, primary, O’hUigin, Colm, additional, Yuki, Yuko, additional, Bashirova, Arman A., additional, Collins, David R., additional, Urbach, Jonathan M., additional, Wolinsky, Steven, additional, Buchbinder, Susan, additional, Kirk, Gregory D., additional, Goedert, James J., additional, Michael, Nelson L., additional, Haas, David W., additional, Deeks, Steven G., additional, Walker, Bruce D., additional, Yu, Xu, additional, and Carrington, Mary, additional
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- 2024
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42. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition
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Vaccari, Monica, Gordon, Shari N, Fourati, Slim, Schifanella, Luca, Liyanage, Namal PM, Cameron, Mark, Keele, Brandon F, Shen, Xiaoying, Tomaras, Georgia D, Billings, Erik, Rao, Mangala, Chung, Amy W, Dowell, Karen G, Bailey-Kellogg, Chris, Brown, Eric P, Ackerman, Margaret E, Vargas-Inchaustegui, Diego A, Whitney, Stephen, Doster, Melvin N, Binello, Nicolo, Pegu, Poonam, Montefiori, David C, Foulds, Kathryn, Quinn, David S, Donaldson, Mitzi, Liang, Frank, Loré, Karin, Roederer, Mario, Koup, Richard A, McDermott, Adrian, Ma, Zhong-Min, Miller, Christopher J, Phan, Tran B, Forthal, Donald N, Blackburn, Matthew, Caccuri, Francesca, Bissa, Massimiliano, Ferrari, Guido, Kalyanaraman, Vaniambadi, Ferrari, Maria G, Thompson, DeVon, Robert-Guroff, Marjorie, Ratto-Kim, Silvia, Kim, Jerome H, Michael, Nelson L, Phogat, Sanjay, Barnett, Susan W, Tartaglia, Jim, Venzon, David, Stablein, Donald M, Alter, Galit, Sekaly, Rafick-Pierre, and Franchini, Genoveffa
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Biomedical and Clinical Sciences ,Immunology ,Good Health and Well Being ,Adaptive Immunity ,Adjuvants ,Immunologic ,Alum Compounds ,Animals ,Immunity ,Innate ,Immunity ,Mucosal ,Immunogenicity ,Vaccine ,Immunoglobulin G ,Interleukin-17 ,Lymphocytes ,Macaca mulatta ,Membrane Glycoproteins ,Random Allocation ,SAIDS Vaccines ,Signal Transduction ,Simian Acquired Immunodeficiency Syndrome ,Simian Immunodeficiency Virus ,Transcriptome ,Viral Envelope Proteins ,Viral Vaccines ,ras Proteins ,Simian immunodeficiency virus ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.
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- 2016
43. Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial
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Dayan, Gustavo H, primary, Rouphael, Nadine, additional, Walsh, Stephen R, additional, Chen, Aiying, additional, Grunenberg, Nicole, additional, Allen, Mary, additional, Antony, Johannes, additional, Asante, Kwaku Poku, additional, Bhate, Amit Suresh, additional, Beresnev, Tatiana, additional, Bonaparte, Matthew I, additional, Celle, Médéric, additional, Ceregido, Maria Angeles, additional, Corey, Lawrence, additional, Dobrianskyi, Dmytro, additional, Fu, Bo, additional, Grillet, Marie-Helene, additional, Keshtkar-Jahromi, Maryam, additional, Juraska, Michal, additional, Kee, Jia Jin, additional, Kibuuka, Hannah, additional, Koutsoukos, Marguerite, additional, Masotti, Roger, additional, Michael, Nelson L, additional, Neuzil, Kathleen M, additional, Reynales, Humberto, additional, Robb, Merlin L, additional, Villagómez Martínez, Sandra M, additional, Sawe, Fredrick, additional, Schuerman, Lode, additional, Tong, Tina, additional, Treanor, John, additional, Wartel, T Anh, additional, Diazgranados, Carlos A, additional, Chicz, Roman M, additional, Gurunathan, Sanjay, additional, Savarino, Stephen, additional, Sridhar, Saranya, additional, Abalos, Karina, additional, Accini, Jose, additional, Aloysia, Naveena, additional, Amuasi, John Humphrey, additional, Ansah, Nana Akosua, additional, Benkeser, David, additional, Berge, Aude, additional, Beyko, Hanna, additional, Bilotkach, Oleksandra, additional, Breuer, Thomas, additional, Bonfanti, Alberto Cadena, additional, Bukusi, Elisabeth, additional, Canter, Richard, additional, Carrillo, Jaime Augusto, additional, Chansinghakul, Danaya, additional, Coux, Florence, additional, Das, Chandan, additional, Das, Santa Kumar, additional, Devlin, Louis, additional, Espinoza, Luis, additional, Fay, Michael, additional, Follmann, Dean, additional, Frago, Carina, additional, Garinga, Agnes, additional, Gilbert, Peter B, additional, Gonzalez, Claudia, additional, Granados, Maria Angelica, additional, Guillery, Lea, additional, Huang, Ying, additional, Hudzina, Kathy, additional, Jain, Manish, additional, Kanodia, Piush, additional, Khandelwal, Nitin, additional, Mutuluuza, Cissy Kityo, additional, Kiweewa, Francis, additional, Kiwanuka, Noah, additional, Kosolsak, Chalit, additional, Kukian, Darshna, additional, Kushwaha, Jitendra Singh, additional, Laot, Thelma, additional, Lopez-Medina, Eduardo, additional, Macareno Arroyo, Hugo, additional, Mandaliya, Kishorchandra, additional, Mamod, Stephanie, additional, Mangarule, Somnath, additional, Martínez, Javier, additional, McClelland, Scott, additional, Menard, Lisa, additional, Mendoza, Sandra, additional, Mohapatra, Satyajit, additional, Moreau, Catherine, additional, Mugo, Nelly, additional, Nduba, Videlis, additional, Noriega, Fernando, additional, Ntege, Patricia Nahirya, additional, Okech, Brenda, additional, Otero, Maria, additional, Ouma, Samuel Gurrion, additional, Oyieko, Janet, additional, Paredes, Mercedes, additional, Pardo, Erwin, additional, Postol, Svitlana, additional, Pekala, David, additional, Peng, Penny, additional, Py, Marie-Laure, additional, Rivas, Enrique, additional, Rivero, Rafael, additional, Rodriguez, Edith, additional, Saleh, Mansoor, additional, Sánchez, Pedro, additional, Sater, Nessryne, additional, Shah, Jinen, additional, Shrestha, Rajeev, additional, Siika, Abraham, additional, Singh, Chandramani, additional, Singh, Veer Bahadur, additional, Tamrakar, Dipesh, additional, Tavares Da-Silva, Fernanda, additional, Otieno Tina, Lucas, additional, Velasquez, Hector, additional, Wabwire, Deo, additional, Wajja, Anne, additional, Zaworski, Elodie, additional, and Zhang, Nianxian, additional
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- 2023
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44. SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses
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Carmen, Joshua M., Shrivastava, Shikha, Lu, Zhongyan, Anderson, Alexander, Morrison, Elaine B., Sankhala, Rajeshwer S., Chen, Wei-Hung, Chang, William C., Bolton, Jessica S., Matyas, Gary R., Michael, Nelson L., Joyce, M. Gordon, Modjarrad, Kayvon, Currier, Jeffrey R., Bergmann-Leitner, Elke, Malloy, Allison M. W., and Rao, Mangala
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- 2021
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45. Determinants of suboptimal [CD4.sup.+] T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV-1 infection
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Handoko, Ryan, Colby, Donn J., Kroon, Eugene, Sacdalan, Carlo, Desouza, Mark, Pinyakorn, Suteeraporn, Prueksakaew, Peeriya, Munkong, Chutharat, Ubolyam, Sasiwimol, Akapirat, Siriwat, Chiarella, Jennifer, Krebs, Shelly, Sereti, Irini, Valcour, Victor, Paul, Robert, Michael, Nelson L., Phanuphak, Nittaya, Ananworanich, Jintanat, and Spudich, Serena
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HIV infections -- Drug therapy -- Physiological aspects ,Antiretroviral agents -- Usage -- Physiological aspects ,CD4 lymphocytes -- Health aspects -- Measurement ,Health - Abstract
Introduction: Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/[mm.sup.3] despite plasma viral suppression. We investigated the frequency and associations of suboptima CD4 recovery after ART started during acute HIV infection (AHI). Methods: Participants who started ART in Fiebig I to V AHI with [greater than or equal to]48 weeks of continuous documented HIV-RNA< 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/[mm.sup.3]), intermediate immune recovery (IIR; 350 [less than or equal to] CD4 < 500) and complete immune recovery (CIR; CD4 [greater than or equal to] 500). Clinical and laboratory parameters were assessed at pre-ART baseline and latest study visit. Additional inflammatory and neurobehavioral end-points were examined at baseline and 96 weeks. Results: Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post-exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre-ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/[mm.sup.3] (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the [CD8.sup.+]T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL-6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. Conclusions: Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre-ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment. Keywords: ARV; Asia; men who have sex with men; LMIC; immunology; HIV care continuum Additional information may be found under the Supporting Information tab for this article., 1 | INTRODUCTION In the era of potent antiretroviral therapy (ART), ongoing HIV replication is adequately suppressed to undetectable levels in appropriately treated individuals. However, up to 30% of ART-treated [...]
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- 2020
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46. Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound
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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
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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 [...]
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- 2020
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47. Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption
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Mitchell, Julie L., Takata, Hiroshi, Muir, Roshell, Colby, Donn J., Kroon, Eugene, Crowell, Trevor A., Sacdalan, Carlo, Pinyakorn, Suteeraporn, Puttamaswin, Suwanna, Benjapornpong, Khunthalee, Trichavaroj, Rapee, Tressler, Randall L., Fox, Lawrence, Polonis, Victoria R., Bolton, Diane L., Maldarelli, Frank, Lewin, Sharon R., Haddad, Elias K., Phanuphak, Praphan, Robb, Merlin L., Michael, Nelson L., de Souza, Mark, Phanuphak, Nittaya, Ananworanich, Jintanat, and Trautmann, Lydie
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Thermo Fisher Scientific Inc. ,Highly active antiretroviral therapy -- Health aspects ,Vorinostat -- Health aspects ,Viremia -- Health aspects ,HIV tests -- Health aspects ,HIV -- Health aspects ,Infection -- Health aspects ,Dendritic cells -- Health aspects ,Maraviroc -- Health aspects ,Virus replication -- Health aspects ,Scientific equipment industry -- Health aspects ,Health care industry - Abstract
Plasmacytoid dendritic cells (pDCs) are robust producers of IFN[alpha] and one of the first immune cells to respond to SIV infection. To elucidate responses to early HIV-1 replication, we studied blood pDCs in 29 HIV-infected participants who initiated antiretroviral therapy during acute infection and underwent analytic treatment interruption (ATI). We observed an increased frequency of partially activated pDCs in the blood before detection of HIV RNA. Concurrent with peak pDC frequency, we detected a transient decline in the ability of pDCs to produce IFN[alpha] in vitro, which correlated with decreased phosphorylation of IFN regulatory factory 7 (IRF7) and NF-[kappa]B. The levels of phosphorylated IRF7 and NF-[kappa]B inversely correlated with plasma IFNA2 levels, implying that pDCs were refractory to in vitro stimulation after IFN[alpha] production in vivo. After ATI, decreased expression of IFN genes in pDCs inversely correlated with the time to viral detection, suggesting that pDC IFN loss is part of an effective early immune response. These data from a limited cohort provide a critical first step in understanding the earliest immune response to HIV-1 and suggest that changes in blood pDC frequency and function can be used as an indicator of viral replication before detectable plasma viremia., Introduction Plasmacytoid dendritic cells (pDCs) are important mediators of the early innate immune response to viral infection through robust production of type I IFNs, particularly IFN[alpha] (1, 2). pDCs recognize [...]
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- 2020
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48. Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor
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Dussupt, Vincent, Sankhala, Rajeshwer S., Gromowski, Gregory D., Donofrio, Gina, De La Barrera, Rafael A., Larocca, Rafael A., Zaky, Weam, Mendez-Rivera, Letzibeth, Choe, Misook, Davidson, Edgar, McCracken, Michael K., Brien, James D., Abbink, Peter, Bai, Hongjun, Bryan, Aubrey L., Bias, Candace Hope, Berry, Irina Maljkovic, Botero, Nubia, Cook, Tanya, Doria-Rose, Nicole A., Escuer, Ariadna Grinyo i, Frimpong, Justice Akuoku, Geretz, Aviva, Hernandez, Mayda, Hollidge, Bradley S., Jian, Ningbo, Kabra, Kareem, Leggat, David J., Liu, Jinyan, Pinto, Amelia K., Rutvisuttinunt, Wiriya, Setliff, Ian, Tran, Ursula, Townsley, Samantha, Doranz, Benjamin J., Rolland, Morgane, McDermott, Adrian B., Georgiev, Ivelin S., Thomas, Rasmi, Robb, Merlin L., Eckels, Kenneth H., Barranco, Elizabeth, Koren, Michael, Smith, Darci R., Jarman, Richard G., George, Sarah L., Stephenson, Kathryn E., Barouch, Dan H., Modjarrad, Kayvon, Michael, Nelson L., Joyce, M. Gordon, and Krebs, Shelly J.
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- 2020
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49. Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques
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Santra, Sampa, Tomaras, Georgia D, Warrier, Ranjit, Nicely, Nathan I, Liao, Hua-Xin, Pollara, Justin, Liu, Pinghuang, Alam, S. Munir, Zhang, Ruijun, Cocklin, Sarah L, Shen, Xiaoying, Duffy, Ryan, Xia, Shi-Mao, Schutte, Robert J, Pemble IV, Charles W, Dennison, S. Moses, Li, Hui, Chao, Andrew, Vidnovic, Kora, Evans, Abbey, Klein, Katja, Kumar, Amit, Robinson, James, Landucci, Gary, Forthal, Donald N, Montefiori, David C, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Rerks-Ngarm, Supachai, Robb, Merlin L, Michael, Nelson L, Kim, Jerome H, Soderberg, Kelly A, Giorgi, Elena E, Blair, Lily, Korber, Bette T, Moog, Christiane, Shattock, Robin J, Letvin, Norman L, Schmitz, Joern E, Moody, M. A, Gao, Feng, Ferrari, Guido, Shaw, George M, Haynes, Barton F, and Douek, Daniel C
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- 2015
50. Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research
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Wieczorek, Lindsay, Krebs, Shelly J, Kalyanaraman, Vaniambadi, Whitney, Stephen, Tovanabutra, Sodsai, Moscoso, Carlos G, Sanders-Buell, Eric, Williams, Constance, Slike, Bonnie, Molnar, Sebastian, Dussupt, Vincent, Alam, S Munir, Chenine, Agnes-Laurence, Tong, Tina, Hill, Edgar L, Liao, Hua-Xin, Hoelscher, Michael, Maboko, Leonard, Zolla-Pazner, Susan, Haynes, Barton F, Pensiero, Michael, McCutchan, Francine, Malek-Salehi, Shawyon, Cheng, R Holland, Robb, Merlin L, VanCott, Thomas, Michael, Nelson L, Marovich, Mary A, Alving, Carl R, Matyas, Gary R, Rao, Mangala, and Polonis, Victoria R
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Vaccine Related ,Infectious Diseases ,Biotechnology ,Prevention ,Immunization ,Vaccine Related (AIDS) ,HIV/AIDS ,3.4 Vaccines ,Prevention of disease and conditions ,and promotion of well-being ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,AIDS Vaccines ,Animals ,Drug Evaluation ,Preclinical ,HIV Antibodies ,HIV Infections ,HIV-1 ,Humans ,Leukocytes ,Mononuclear ,Molecular Sequence Data ,Neutralization Tests ,Rabbits ,Vaccination ,env Gene Products ,Human Immunodeficiency Virus ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
UnlabelledEliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 infections are subtype C, and novel antigenic properties have been described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was developed as a research reagent and candidate immunogen. The gp145 envelope is a novel immunogen with a fully intact membrane-proximal external region (MPER), extended by a polylysine tail. Soluble gp145 was enriched for trimers that yielded the expected "fan blade" motifs when visualized by cryoelectron microscopy. CO6980v0c22 gp145 reacts with the 4E10, PG9, PG16, and VRC01 HIV-1 neutralizing monoclonal antibodies (MAbs), as well as the V1/V2-specific PGT121, 697, 2158, and 2297 MAbs. Different gp145 oligomers were tested for immunogenicity in rabbits, and purified dimers, trimers, and larger multimers elicited similar levels of cross-subtype binding and neutralizing antibodies to tier 1 and some tier 2 viruses. Immunized rabbit sera did not neutralize the highly resistant CO6980v0c22 pseudovirus but did inhibit the homologous infectious molecular clone in a peripheral blood mononuclear cell (PBMC) assay. This Env is currently in good manufacturing practice (GMP) production to be made available for use as a clinical research tool and further evaluation as a candidate vaccine.ImportanceAt present, the product pipeline for HIV vaccines is insufficient and is limited by inadequate capacity to produce large quantities of vaccine to standards required for human clinical trials. Such products are required to evaluate critical questions of vaccine formulation, route, dosing, and schedule, as well as to establish vaccine efficacy. The gp145 Env protein presented in this study forms physical trimers, binds to many of the well-characterized broad neutralizing MAbs that target conserved Env epitopes, and induce cross-subtype neutralizing antibodies as measured in both cell line and primary cell assays. This subtype C Env gp145 protein is currently undergoing good manufacturing practice production for use as a reagent for preclinical studies and for human clinical research. This product will serve as a reagent for comparative studies and may represent a next-generation candidate HIV immunogen.
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- 2015
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