Journal ArticleDOI
Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination
Dan H. Barouch,Sampa Santra,Jörn E. Schmitz,Marcelo J. Kuroda,Tong-Ming Fu,Wendeline Wagner,Miroslawa Bilska,Abie Craiu,Xin Xiao Zheng,Georgia R. Krivulka,Kristin Beaudry,Michelle A. Lifton,Christine E. Nickerson,Wendy L. Trigona,Kara Punt,Dan C. Freed,Liming Guan,Sheri Dubey,Danilo R. Casimiro,Adam J. Simon,Mary-Ellen Davies,Michael Chastain,Terry B. Strom,Rebecca Gelman,David C. Montefiori,Mark G. Lewis,Emilio A. Emini,John W. Shiver,Norman L. Letvin +28 more
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TLDR
The protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys is reported, with no evidence of clinical disease or mortality after challenge.Abstract:
With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+ T cells, no virus-specific CD4+ T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+ T cell counts, preserved virus-specific CD4+ T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge.read more
Citations
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Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity.
John W. Shiver,Tong-Ming Fu,Ling Chen,Danilo R. Casimiro,Mary-Ellen Davies,Robert K. Evans,Zhiqiang Zhang,Adam J. Simon,Wendy L. Trigona,Sheri Dubey,Lingyi Huang,Virginia Harris,Romnie Long,Xiaoping Liang,Larry Handt,William A. Schleif,Lan Zhu,Daniel C. Freed,Natasha Persaud,Liming Guan,Kara Punt,Aimin Tang,Minchun Chen,Keith A. Wilson,Kelly B. Collins,Gwendolyn J. Heidecker,V. Rose Fernandez,Helen C. Perry,Joseph G. Joyce,Karen M. Grimm,James C. Cook,Paul M. Keller,Denise S. Kresock,Henryk Mach,Robert D. Troutman,Lynne Isopi,Donna M. Williams,Zheng Xu,Kathryn E. Bohannon,David B. Volkin,David C. Montefiori,Ayako Miura,Georgia R. Krivulka,Michelle A. Lifton,Marcelo J. Kuroda,Jörn E. Schmitz,Norman L. Letvin,Michael J. Caulfield,Andrew J. Bett,Rima Youil,David C. Kaslow,Emilio A. Emini +51 more
TL;DR: The replication-defective adenovirus is a promising vaccine vector for development of an HIV-1 vaccine and elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector.
Journal ArticleDOI
Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine.
Rama Rao Amara,Francois Villinger,John D. Altman,Shari L. Lydy,Shawn P. O'Neil,Silvija I. Staprans,David C. Montefiori,Yan Xu,James G. Herndon,Linda S. Wyatt,Maria Angelito Candido,Natalia Kozyr,Patricia L. Earl,James M. Smith,Hak-Ling Ma,Hak-Ling Ma,Bennett D. Grimm,Michael L. Hulsey,Joseph I. Miller,Harold M. McClure,Janet M. McNicholl,Bernard Moss,Harriet L. Robinson +22 more
TL;DR: DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster controlled a highly pathogenic immunodeficiency virus challenge in a rhesus macaque model, providing hope that a relatively simple multiprotein DNA/MVA vaccine can help to control the acquired immune deficiency syndrome epidemic.
Journal ArticleDOI
DNA vaccines: ready for prime time?
TL;DR: A productive future for DNA vaccine technology is suggested as more optimized constructs, better trial designs and improved platforms are being brought into the clinic.
Journal ArticleDOI
Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level
Corey Moore,Mina John,Ian James,Frank T. Christiansen,Frank T. Christiansen,Campbell S. Witt,Simon Mallal +6 more
TL;DR: A fundamental role is supported for HLA-restricted immune responses in driving and shaping HIV-1 evolution in vivo and at a population level the degree of HLA–associated selection in viral sequence was predictive of viral load.
Journal ArticleDOI
Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: relationship to viral load in untreated HIV infection
Michael R. Betts,David R. Ambrozak,Daniel C. Douek,Sebastian Bonhoeffer,Jason M. Brenchley,Joseph P. Casazza,Richard A. Koup,Louis J. Picker +7 more
TL;DR: Overall frequencies of HIV-specific T cells are not the sole determinant of immune-mediated protection in HIV-infection, and a positive correlation was identified between the plasma viral load and the total HIV-, Env-, and Nef-specific CD8+ T-cell frequency.
References
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TL;DR: It is suggested that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and a role for CTL in protective immunity to HIV- 1 in vivo is indicated.
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Heterologous protection against influenza by injection of DNA encoding a viral protein
Jeffrey B. Ulmer,John J. Donnelly,Suezanne E. Parker,Gary Rhodes,Philip L. Felgner,V. J. Dwarki,Stanislaw H. Gromkowski,R. Randall Deck,Corrille M. DeWitt,Arthur Friedman,Linda A. Hawe,Karen R. Leander,Douglas Martinez,Helen C. Perry,John W. Shiver,Donna L. Montgomery,Margaret A. Liu +16 more
TL;DR: To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleop protein was injected into the quadriceps of BALB/c mice and resulted in the generation of nucleoprotein-specific CTLs.
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