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Virus-specific T cell

Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
March 13, 2018: Journal of Infectious Diseases
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
D Lapuente, M Storcksdieck Genannt Bonsmann, A Maaske, V Stab, V Heinecke, K Watzstedt, R Heß, A M Westendorf, W Bayer, C Ehrhardt, M Tenbusch
A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1β or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1β enhanced HA-specific antibody responses including strain-specific neutralizing antibodies...
March 15, 2018: Mucosal Immunology
Matthew J Atherton, Kyle B Stephenson, Jake K Nikota, Qian N Hu, Andrew Nguyen, Yonghong Wan, Brian D Lichty
Human papilloma virus (HPV)-associated cancer is a significant global health burden and despite the presence of viral transforming antigens within neoplastic cells, therapeutic vaccinations are ineffective for advanced disease. HPV positive TC1 cells are susceptible to viral oncolysis by MG1-E6E7, a custom designed oncolytic Maraba virus. Epitope mapping of mice vaccinated with MG1-E6E7 enabled the rational design of synthetic long peptide (SLP) vaccines against HPV16 and HPV18 antigens. SLPs were able to induce specific CD8+ immune responses and the magnitude of these responses significantly increased when boosted by MG1-E6E7...
March 12, 2018: Vaccine
Weiping Cao, Margarita Mishina, Samuel Amoah, Wadzanai P Mboko, Caitlin Bohannon, James McCoy, Suresh K Mittal, Shivaprakash Gangappa, Suryaprakash Sambhara
Avian influenza virus infection is a serious public health threat and preventive vaccination is the most cost-effective public health intervention strategy. Unfortunately, currently available unadjuvanted avian influenza vaccines are poorly immunogenic and alternative vaccine formulations and delivery strategies are in urgent need to reduce the high risk of avian influenza pandemics. Cationic polymers have been widely used as vectors for gene delivery in vitro and in vivo. In this study, we formulated H5N1 influenza vaccines with GenJet™ or in vivo-jetPEI® , and showed that these formulations significantly enhanced the immunogenicity of H5N1 vaccines and conferred protective immunity in a mouse model...
November 2018: Drug Delivery
Lina Rustanti, Hongping Jin, Dongsheng Li, Mary Lor, Haran Sivakumaran, David Harrich
Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral mRNA from the nucleus to the cytoplasm and transcription of viral mRNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2 (a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-ZsGreen1 to human T cells...
March 14, 2018: Virologica Sinica
Mathew A Cherian, Sydney Olson, Hemalatha Sundaramoorthi, Kitra Cates, Xiaogang Cheng, John Harding, Andrew Martens, Grant A Challen, Manoj Tyagi, Lee Ratner, Daniel Rauch
The human T cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, likely as a result of specific immuno-editing, Tax expression is downregulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL, and the K59R mutation is the most common single-nucleotide variation in IRF4 and is found exclusively in ATL...
March 14, 2018: Journal of Biological Chemistry
Denise C Hsu, Kimberly F Breglio, Luxin Pei, Chun-Shu Wong, Bruno B Andrade, Virginia Sheikh, Margery Smelkinson, Constantinos Petrovas, Adam Rupert, Leonardo Gil-Santana, Adrian Zelazny, Steven M Holland, Kenneth Olivier, Daniel Barber, Irini Sereti
Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods: We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with pulmonary MAC infection...
March 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
J Jeong, I Kang, S Kim, S-J Park, K H Park, T Oh, S Yang, C Chae
The objective of this study was to determine the efficacy of a commercially available porcine reproductive and respiratory syndrome virus (PRRSV)-1 modified-live virus (MLV) vaccine against PRRSV-1 and PRRSV-2 challenge in late-term pregnancy gilts. Gilts were vaccinated with the PRRSV-1 MLV vaccine at 4 weeks prior to breeding and then challenged intranasally with PRRSV-1 or PRRSV-2 at 93 days of gestation. After PRRSV-1 challenge, vaccinated pregnant gilts had a significantly longer gestation period, significantly higher numbers of live-born and weaned piglets and a significantly lower number of stillborn piglets at birth compared to unvaccinated pregnant gilts...
March 13, 2018: Transboundary and Emerging Diseases
Hiroyuki Abe, Ruri Saito, Takashi Ichimura, Akiko Iwasaki, Sho Yamazawa, Aya Shinozaki-Ushiku, Teppei Morikawa, Tetsuo Ushiku, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) frequently harbors dense lymphocytic infiltration, suggesting a specific microenvironment allowing coexistence with tumor immunity. CD47, which mediates the "do not eat me" signal in innate immunity, is also important in adaptive anti-tumor immunity. We investigated the significance of CD47 in EBVaGC compared with EBV-negative gastric cancer and the correlation with various immune cells. By immunohistochemistry of CD47, high, low, and negative expression was observed in 24, 63, and 12% of EBVaGC (n = 41), while 11, 49, and 39% of EBV-negative gastric cancer (n = 262), respectively, indicating that high expression of CD47 in cancer cells was significantly frequent and increased in EBVaGC (P = 0...
March 13, 2018: Virchows Archiv: An International Journal of Pathology
C G Bien
The paraneoplastic and autoimmune encephalitides are now well-established entities. Detection of neural autoantibodies enables specific diagnoses, provides information on the underlying disease pathophysiology, immunological treatability and the likelihood of a tumor being the underlying cause. This is true for the "high ranking" neural antibodies that have been established in the context of circumscribed clinical images and in consideration of large control groups, have been found in the same way by other laboratories and they respond to immunotherapy...
March 13, 2018: Der Nervenarzt
Monica Vaccari, Genoveffa Franchini
Germinal centers (GCs) are organized lymphoid tissue microstructures where B cells proliferate and differentiate into memory B cells and plasma cells. A few distinctive subsets of highly specialized T cells gain access to the GCs by expressing the B cell zone-homing C-X-C chemokine receptor type 5 (CXCR5) while losing the T cell zone-homing chemokine receptor CCR7. Help from T cells is critical to induce B cell proliferation and somatic hyper mutation and to limit GC reactions. CD4+ T follicular helper (TFH ) cells required for the formation of GCs and for the generation of long-lived, high-affinity B cells...
2018: Frontiers in Immunology
Tetsuo Koshizuka, Takahiro Kobayashi, Ken Ishioka, Tatsuo Suzutani
Nedd4 is a family of ubiquitin E3 ligases that regulate numerous cellular processes. In this report, we showed that alpha- and beta-herpesviruses have membrane proteins that regulate the function of the Nedd4 family members. Although the homology search score was quite low, UL56 of herpes simplex virus type 1 and 2, ORF0 of varicella-zoster virus, UL42 of human cytomegalovirus, and U24 of human herpesvirus 6A, 6B, and 7 all possess at least one PPxY (PY) motif in their cytoplasmic domain, and are able to bind with Itch, a member of the Nedd4 family...
March 13, 2018: Scientific Reports
Li Liu, Xuyan Zhang, Sizhou Feng
Epstein-Barr virus related post-transplant lymphoproliferative disorders (EBV-PTLDs) are rare but potentially fatal complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by uncontrolled proliferation of EBV-infected lymphocytes. The most frequent risk factors include T cell depletion of graft, HLA mismatch, severe graft versus host disease (GVHD), EBV sero-mismatch (recipient-/donor+) and so on. EBV-PTLDs commonly manifest as fever and lymphadenopathy and may rapidly progress to multi-organ failure and even death...
March 9, 2018: Biology of Blood and Marrow Transplantation
Anthony L Cunningham, Thomas C Heineman, Himal Lal, Olivier Godeaux, Roman Chlibek, Shinn-Jang Hwang, Janet E McElhaney, Timo Vesikari, Charles Andrews, Won Suk Choi, Meral Esen, Hideyuki Ikematsu, Martina Kovac Choma, Karlis Pauksens, Stéphanie Ravault, Bruno Salaun, Tino F Schwarz, Jan Smetana, Carline Vanden Abeele, Peter Van den Steen, Ilse Vastiau, Lily Yin Weckx, Myron J Levin
Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials ( NCT01165177; NCT01165229). We present immunogenicity results from those trials. Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months (M) apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of the 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in sub-cohorts for humoral (n=3293) and cell-mediated (n=466) immunogenicity...
February 26, 2018: Journal of Infectious Diseases
Elisenda Alari-Pahissa, Antía Moreira, Ana Zabalza, Roberto Alvarez-Lafuente, Elvira Munteis, Andrea Vera, Rafael Arroyo, Jose C Alvarez-Cermeño, Luisa Maria Villar, Miguel López-Botet, Jose E Martínez-Rodríguez
BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has been recently associated with a lower multiple sclerosis (MS) susceptibility, remaining controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in early MS as compared to non-early MS patients, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses...
March 12, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
John J Miles, Mai Ping Tan, Garry Dolton, Emily Sj Edwards, Sarah Ae Galloway, Bruno Laugel, Mathew Clement, Julia Makinde, Kristin Ladell, Katherine K Matthews, Thomas S Watkins, Katie Tungatt, Yide Wong, Han Siean Lee, Richard J Clark, Johanne M Pentier, Meriem Attaf, Anya Lissina, Ann Ager, Awen Gallimore, Pierre J Rizkallah, Stephanie Gras, Jamie Rossjohn, Scott R Burrows, David K Cole, David A Price, Andrew K Sewell
Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic "mimics" using subunits that do not exist in the natural world. We developed a platform based on D-amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus...
March 12, 2018: Journal of Clinical Investigation
John Joseph Heath, Neva Jennifer Fudge, Maureen Elizabeth Gallant, Michael David Grant
Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, age-related morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other age-related morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIV-infected individuals seropositive for anti-CMV antibodies...
2018: Frontiers in Immunology
Maite Ramírez, Saritza Santos, Osmarie Martínez, Ricardo Rodríguez, Eric Miranda, Willy D Ramos-Perez, Miguel Otero
Poxviruses are complex dsDNA viruses with over 200 genes, many of them with unknown role in the stimulation of immune responses. Among these, the vaccinia virus (VACV) L3L ORF encodes an essential protein for the transcription of the VACV early genes. To the best of our knowledge, the immune response elicited by L3 has not been characterized. In this regard, our data describes a DNA L3-coding plasmid (pL3L) that stimulates both, humoral- and cell-mediated immune responses in a mouse model. Cell-mediated immune responses were measured by IFN-γ and IL-4 ELISPOT assays...
March 7, 2018: Vaccine
Waranyoo Phoolcharoen, Ashley C Banyard, Christophe Prehaud, David Selden, Guanghui Wu, Colin P D Birch, Tim H Szeto, Monique Lafon, Anthony R Fooks, Julian K-C Ma
Rabies causes more than 60,000 human deaths annually in areas where the virus is endemic. Importantly, rabies is one of the few pathogens for which there is no treatment following the onset of clinical disease with the outcome of infection being death in almost 100% of cases. Whilst vaccination, and the combination of vaccine and rabies immunoglobulin treatment for post-exposure administration are available, no tools have been identified that can reduce or prevent rabies virus replication once clinical disease has initiated...
March 6, 2018: Vaccine
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