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1. Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication

Author

Huanbin Xu, Anne-Marie Andersson, Emeline Ragonnaud, Ditte Boilesen, Anders Tolver, Benjamin Anderschou Holbech Jensen, James L. Blanchard, Alfredo Nicosia, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Allan Randrup Thomsen, Jan Pravsgaard Christensen, Ronald S. Veazey, and Peter Johannes Holst

Subjects
Heterologous viral vectored prime-boost immunization, Genetic adjuvant, Medicine, Medicine (General), R5-920
Abstract

Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P = 0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia.

Published
2017
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2. Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication

Author

Alfredo Nicosia, James Blanchard, Benjamin A. H. Jensen, Ronald S. Veazey, Stefano Colloca, Jan Pravsgaard Christensen, Emeline Ragonnaud, Allan Randrup Thomsen, Anders Tolver, Antonella Folgori, Peter Johannes Holst, Ditte Rahbæk Boilesen, Huanbin Xu, Anne-Marie C. Andersson, Riccardo Cortese, Xu, H, Andersson, Am, Ragonnaud, E, Boilesen, D, Tolver, A, Jensen, Bah, Blanchard, Jl, Nicosia, A, Folgori, A, Colloca, S, Cortese, R, Thomsen, Ar, Christensen, Jp, Veazey, R, and Holst, Pj.

Subjects
0301 basic medicine, Naive T cell, T cell, lcsh:Medicine, Viremia, Heterologous viral vectored prime-boost immunization, Genetic adjuvant, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, medicine, lcsh:R5-920, lcsh:R, virus diseases, General Medicine, medicine.disease, Virology, 3. Good health, Vaccination, 030104 developmental biology, medicine.anatomical_structure, Viral replication, Immunology, lcsh:Medicine (General), T-cell vaccine, 030215 immunology
Abstract

Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naive T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia.

Published
2017
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3. Contributors

Author

Valérie Abadie, Clara Abraham, David H. Adams, William W. Agace, Jennifer Alexander-Brett, Omar Alkhairy, Ines Ambite, Deborah J. Anderson, David Artis, Robert L. Atmar, Laetitia Aymeric, Claus Bachert, Jantine E. Bakema, Kristi Baker, Kenneth W. Beagley, A.D. Befus, Mats Bemark, M. Cecilia Berin, Margot Berings, Jay A. Berzofsky, Martin Bilej, Nabanita Biswas, Richard S. Blumberg, John Bienenstock, Dimitrios Bogdanos, Monica Boirivant, Kobporn Boonnak, Ken R. Bracke, Per Brandtzaeg, Jonathan Braun, Marie-Agnès Bringer, Andrew J. Broadbent, Richard Bronson, Guy G. Brusselle, Judith N. Bulmer, J.E. Butler, Paul A. Cardenas, John J. Cebra, Marina Cella, Andrea Cerutti, Stephen J. Challacombe, Kuldeep Chattha, Hilde Cheroutre, Tsutomu Chiba, Alejo Chorny, John D. Clements, Marco Colonna, William O.C. Cookson, Lynette B. Corbeil, Blaise Corthésy, Allan W. Cripps, Koen van Crombruggen, Andre Pires da Cunha, Susanna Cunningham-Rundles, Roy Curtiss, Arlette Darfeuille-Michaud, Wouter J. de Jonge, Livija Deban, Timothy L. Denning, James P. Di Santo, Andreas Diefenbach, Victor J. DiRita, Jordan Downey, Ming-Qing Du, Karen L. Edelblum, Marjolein van Egmond, H.-J. Epple, Sidonia Fagarasan, John V. Fahey, Michael J. Ferris, Stefan Fichtner-Feigl, Paul L. Fidel, Melanie Flach, Richard Flavell, Howard B. Fleit, Genoveffa Franchini, Lucy C. Freytag, Anja Fuchs, kohtaro Fujihashi, Ivan J. Fuss, Nicola Gagliani, Marta Rodriguez Garcia, Wendy S. Garrett, M. Eric Gershwin, Philippe Gevaert, Maree Gleeson, Gabriela Godaly, Randall M. Goldblum, Naina Gour, Mayda Gursel, George Hajishengallis, Hamida Hammad, Lennart Hammarström, Arno Hänninen, Lars Å. Hanson, Adrian Hayday, Ronit Herzog, Douglas C. Hodgins, Stephen T. Holgate, Jan Holmgren, Michael J. Holtzman, Edward W. Hook, Samuel Huber, Julia L. Hurwitz, Juraj Ivanyi, Akiko Iwasaki, Bana Jabri, Susan Jackson, Jonathan Jacobs, Sirpa Jalkanen, Edward N. Janoff, Ann E. Jerse, Mangalakumari Jeyanathan, Bruce A. Julian, Imre Kacskovics, Charlotte S. Kaetzel, Charu Kaushic, Brian L. Kelsall, Sarah Kessans, Rebecca Kesselring, Mogens Kilian, Hiroshi Kiyono, Dennis M. Klinman, Marina Korotkova, Mitchell Kronenberg, Olga Krysko, Yuichi Kurono, Miloslav Kverka, Bart N. Lambrecht, Michael E. Lamm, Olivier Lantz, Gendie E. Lash, E.C. Lavelle, Leo Lefrancois, Patrick S.C. Leung, Myron M. Levine, David J. Lim, John Lippolis, Nancy A. Louis, Andrew D. Luster, Nataliya Lutay, Nils Lycke, Andrew J. Macpherson, Nicholas J. Mantis, Harold Marcotte, David H. Martin, Hugh S. Mason, Helen M. Massa, Nobuyuki Matoba, Lloyd Mayer, Craig L. Maynard, M. Juliana McElrath, C. McEntee, Jerry R. McGhee, Michael A. McGuckin, Jiri Mestecky, Zamaneh Mikhak, Robert D. Miller, Zina Moldoveanu, Paul C. Montgomery, Tsafrir Mor, Markus F. Neurath, Katrijn Neyt, Lindsay K. Nicholson, Jan Novak, Stella Nowicki, D.T. O’Hagan, Nancy L. O’Sullivan, Pearay Ogra, Carlos Orihuela, André J. Ouellette, Robert L. Owen, Oliver Pabst, Charles A. Parkos, Viviana Parreño, Mickey V. Patel, Claudina Perez-Novo, Darren J. Perkins, Calman Prussin, Jeffrey Pudney, Sukanya Raghavan, Pascal Rainard, Sasirekha Ramani, Troy D. Randall, Milan Raska, Gourapura J. Renukaradhya, Maria Rescigno, Kenneth L. Rosenthal, Marc E. Rothenberg, Frank M. Ruemmele, Michael W. Russell, Linda J. Saif, Irene Salinas, Marko Salmi, Henri Salmon, Hugh A. Sampson, Philippe Sansonetti, T. Schneider, Nicolas Serafini, Dolly Sharma, Zheng Shen, Hai Ning Shi, Penelope J. Shirlaw, Sourima B. Shivhare, Phillip D. Smith, Patrick M. Smith, Daniel J. Smith, Lesley E. Smythies, Jo Spencer, Warren Strober, Kanta Subbarao, Catharina Svanborg, Ann-Mari Svennerholm, Martin A. Taubman, Esbjörn Telemo, Martin H. Thornhill, David J. Thornton, Eva Thuenemann, Helena Tlaskalova-Hogenova, Debra Tristram, Palak Trivedi, Elaine Tuomanen, Jaroslav Turanek, Jerrold R. Turner, Brian J. Underdown, Mary J. van Helden, Ronald S. Veazey, Elena F. Verdu, Anastasia Vlasova, Harissios Vliagoftis, Stefanie N. Vogel, W. Allan Walker, Xiaolei Wang, Tomohiro Watanabe, Casey T. Weaver, Howard L. Weiner, Jerry M. Wells, Ting Wen, Judith Whittum-Hudson, Jeffrey A. Whitsett, Ifor R. Williams, Marsha Wills-Karp, Charles R. Wira, Jenny M. Woof, Andrew C. Wotherspoon, Zhou Xing, Huanbin Xu, Colby Zaph, Sebastian Zeissig, and M. Zeitz

Published
2015
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4. Simian Immunodeficiency Virus Infection and Mucosal Immunity

Author

Ronald S. Veazey, Xiaolei Wang, and Huanbin Xu

Subjects
Innate immune system, animal diseases, viruses, T cell, Human immunodeficiency virus (HIV), virus diseases, Simian immunodeficiency virus, Biology, Acquired immune system, medicine.disease_cause, Virology, Immune system, medicine.anatomical_structure, Mucosal immunology, Infectious disease (medical specialty), Immunology, medicine
Abstract

Research into human immunodeficiency virus (HIV) and its predecessor simian immunodeficiency virus (SIV) has fundamentally changed the way we think about infectious disease. SIV and its predecessors have co-evolved with primates for millennia and have become adapted to thwart virtually every arm of the immune system, particularly key aspects of the immune system that nature and vaccines utilize to combat infections. These viruses also replicate and mutate at a phenomenal rate, further evading the much slower adaptive immune system. On the positive side, advances in biomedical research, largely spawned by research into these viruses, have led to remarkable advances in genetic engineering, medicine, and biology. However, it is increasingly clear that SIV and its relatives have shaped the evolution of primate immune systems for millennia, and significant breakthroughs in technology, immunology, and vaccinology will be required to eradicate the latest deadly version of SIV, better known as HIV-1.

Published
2015
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