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https://www.readbyqxmd.com/read/28635592/type-specific-l1-virus-like-particle-mediated-protection-of-horses-from-experimental-bovine-papillomavirus-1-induced-pseudo-sarcoid-formation-is-long-lasting
#1
Julia Harnacker, Edmund K Hainisch, Saeed Shafti-Keramat, Reinhard Kirnbauer, Sabine Brandt
Equine sarcoids are common therapy-resistant skin tumours induced by bovine papillomavirus type 1 or 2 (BPV1, BPV2) infection. We have previously shown that prophylactic vaccination with BPV1 L1 virus-like particles (VLPs) efficiently protects horses from experimental BPV1-induced pseudo-sarcoid development. Here, we assessed BPV1 L1 VLP vaccine-mediated long-term protection from experimental tumour formation in seven horses 5 years after immunization with three different doses of BPV1 L1 VLPs, and three unvaccinated control animals...
June 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28634781/infectious-disease-surveillance-in-the-woylie-bettongia-penicillata
#2
Kim Skogvold, Kristin S Warren, Bethany Jackson, Carly S Holyoake, Kathryn Stalder, Joanne M Devlin, Simone D Vitali, Adrian F Wayne, Alistair Legione, Ian Robertson, Rebecca J Vaughan-Higgins
Wild populations of the critically endangered woylie (Bettongia penicillata) recently declined by 90% in southwest Western Australia. Increased predation is the leading hypothesis for decline, but disease may be playing a role increasing susceptibility to predation. To explore this possibility, we surveyed woylie populations in the wild, in captivity and in a predator-free sanctuary for exposure to, and infection with, four known pathogens of macropods: herpesviruses, Wallal and Warrego orbiviruses, and Toxoplasma gondii...
June 20, 2017: EcoHealth
https://www.readbyqxmd.com/read/28634748/exposure-response-relationship-of-ramucirumab-in-east-asian-patients-from-rainbow-a-randomized-clinical-trial-in-second-line-treatment-of-gastric-cancer
#3
Tae You Kim, Chia-Jui Yen, Salah-Eddin Al-Batran, David Ferry, Ling Gao, Yanzhi Hsu, Rebecca Cheng, Mauro Orlando, Atsushi Ohtsu
BACKGROUND: Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m(2) paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure-response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial...
June 20, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#4
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28633988/a-cross-clade-h5n1-influenza-a-virus-neutralizing-monoclonal-antibody-binds-to-a-novel-epitope-within-the-vestigial-esterase-domain-of-hemagglutinin
#5
Subha Sankar Paul, Chee-Keng Mok, Tze-Minn Mak, Oi-Wing Ng, James Odame Aboagye, Teddy John Wohlbold, Florian Krammer, Yee-Joo Tan
The sporadic outbreaks of highly pathogenic H5N1 avian influenza virus have raised public health concerns. Monoclonal antibodies (MAbs) against hemagglutinin (HA) have been increasingly used successfully for therapeutic purposes. Previously, MAb 9F4, generated against clade 1 H5N1 HA, was observed to have cross-clade neutralizing efficacy and inhibited viral entry by preventing the pH-mediated conformational change of HA. Furthermore, mouse-human chimeric MAb 9F4 was found to retain high degrees of neutralizing activity...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28633892/seropositivity-to-non-vaccine-incorporated-genotypes-induced-by-the-bivalent-and-quadrivalent-hpv-vaccines-a-systematic-review-and-meta-analysis
#6
Sara L Bissett, Anna Godi, Mark Jit, Simon Beddows
BACKGROUND: Human papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes...
June 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#7
REVIEW
Florian C Kurschus, Sonja Moos
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis...
June 15, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633457/an-ha-stem-antibody-medi8852-prevents-and-controls-disease-and-limits-transmission-of-pandemic-influenza-viruses
#8
C I Paules, S Lakdawala, J M McAuliffe, M Paskel, L Vogel, N L Kallewaard, Q Zhu, K Subbarao
Background: MEDI8852 is a novel MAb which neutralizes both group I and group II influenza A viruses (IAV) in vitro. We evaluated whether MEDI8852 was effective for prophylaxis and therapy against representative group I (H5N1) and group II (H7N9) pandemic IAV in mice and ferrets and could be used to block transmission of influenza H1N1pdm09 in ferrets, compared to an irrelevant control MAb R347 and oseltamivir. Results: MEDI8852 was effective for prophylaxis and treatment of H7N9 and H5N1 infection in mice, with a clear dose-dependent response and treatment with MEDI8852 24, 48 or 72 h post-infection (hpi) was superior to oseltamivir for H5N1...
June 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28632942/the-glycans-mediated-mechanism-on-the-interactions-of-gp120-with-cd4-and-antibody-insights-from-molecular-dynamics-simulation
#9
Yan Zhang, Yuzhen Niu, Jia Qi Tian, Xuewei Liu, Xiaojun Yao, Huanxiang Liu
N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). However, it is unknown the action mechanism of two glycans. To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamics simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan and without glycan were performed...
June 20, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28631594/human-picornaviruses-associated-with-neurological-diseases-and-their-neutralization-by-antibodies
#10
Maria Anastasina, Aušra Domanska, Kaia Palm, Sarah Butcher
Picornaviruses are the most commonly encountered infectious agents in mankind. They typically cause mild infections of the gastrointestinal or respiratory tract, but sometimes also invade the central nervous system. There, they can cause severe diseases with long-term sequelae and even be lethal. The most infamous picornavirus is poliovirus, for which significant epidemics of poliomyelitis were reported from the end of the nineteenth century. A successful vaccination campaign has brought poliovirus close to eradication, but neurological diseases caused by other picornaviruses have increasingly been reported since the late 1990s...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28631593/a-denv-2-type-specific-monoclonal-antibody-binds-to-the-denv-complex-reactive-antigenic-site-on-envelope-protein-domain-3
#11
Vanessa V Sarathy, Trevor J Pitcher, Gregory D Gromowski, John T Roehrig, Alan D T Barrett
The Dengue virus (DENV) envelope (E) protein is the major component of the viral surface and is structurally subdivided into three domains, ED1, ED2 and ED3. ED3 elicits potent neutralizing antibodies and contains two major antigenic sites: the DENV-type-specific and DENV-complex-reactive antigenic sites. Each site is composed of a limited subset of residues that are required for monoclonal antibody (mAb) binding. Here we show that DENV-2-type-specific mAb 9A3D-8 utilizes the functionally critical residues K307, V308, K310, I312, P332, L387, L389 and N390 for ED3 binding...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28630473/impact-of-antigen-density-on-the-binding-mechanism-of-igg-antibodies
#12
Maya Hadzhieva, Anastas D Pashov, Srinivas Kaveri, Sébastien Lacroix-Desmazes, Hugo Mouquet, Jordan D Dimitrov
The density and distribution pattern of epitopes at the surface of pathogens have a profound impact on immune responses. Although multiple lines of evidence highlight the significance of antigen surface density for antibody binding, a quantitative description of its effect on recognition mechanisms is missing. Here, we analyzed binding kinetics and thermodynamics of six HIV-1 neutralizing antibodies as a function of the surface density of envelope glycoprotein gp120. Antibodies that recognize gp120 with low to moderate binding affinity displayed the most pronounced sensitivity to variation in antigen density, with qualitative and substantial quantitative changes in the energetics of the binding process as revealed by non-equilibrium and equilibrium thermodynamic analyses...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630325/convergent-immunological-solutions-to-argentine-hemorrhagic-fever-virus-neutralization
#13
Antra Zeltina, Stefanie A Krumm, Mehmet Sahin, Weston B Struwe, Karl Harlos, Jack H Nunberg, Max Crispin, Daniel D Pinschewer, Katie J Doores, Thomas A Bowden
Transmission of hemorrhagic fever New World arenaviruses from their rodent reservoirs to human populations poses substantial public health and economic dangers. These zoonotic events are enabled by the specific interaction between the New World arenaviral attachment glycoprotein, GP1, and cell surface human transferrin receptor (hTfR1). Here, we present the structural basis for how a mouse-derived neutralizing antibody (nAb), OD01, disrupts this interaction by targeting the receptor-binding surface of the GP1 glycoprotein from Junín virus (JUNV), a hemorrhagic fever arenavirus endemic in central Argentina...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630079/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-lessons-from-the-antibody-response-to-hiv-1
#14
Gabriel D Victora, Hugo Mouquet
Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630077/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-breaking-through-immunity-s-glass-ceiling
#15
Garnett Kelsoe, Barton F Haynes
A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have induced bnAbs and few or none of these vaccine-elicited HIV-1 antibodies carry the high frequencies of V(D)J mutations characteristic of bnAbs. Do the high frequencies of mutations characteristic of naturally induced bnAbs represent a fundamental barrier to the induction of bnAbs by vaccines? Recent studies suggest that high frequencies of V(D)J mutations can be achieved by serial vaccination strategies...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630076/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-is-affinity-maturation-a-self-defeating-process-for-eliciting-broad-protection
#16
Christopher T Stamper, Patrick C Wilson
Vaccinations are one of the greatest success stories of modern medicine, saving millions of lives since their widespread adoption. However, several diseases continue to elude highly effective vaccination strategies. Chief among these are human immunodeficiency virus (HIV) and influenza (flu), both of which will require vaccines that can guide the creation of highly mutated, broadly neutralizing antibodies (bnAbs). The generation of bnAbs is hindered by our inability to effectively drive the high levels of affinity maturation required to achieve them in a large number of cells...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28629988/4-azidocytidine-r1479-inhibits-henipaviruses-and-other-paramyxoviruses-with-high-potency
#17
Anne L Hotard, Biao He, Stuart T Nichol, Christina F Spiropoulou, Michael K Lo
The henipaviruses Nipah virus and Hendra virus are highly pathogenic zoonotic paramyxoviruses which have caused fatal outbreaks of encephalitis and respiratory disease in humans. Despite the availability of a licensed equine Hendra virus vaccine and a neutralizing monoclonal antibody shown to be efficacious against henipavirus infections in non-human primates, there remains no approved therapeutics or vaccines for human use. To explore the possibility of developing small-molecule nucleoside inhibitors against henipaviruses, we evaluated the antiviral activity of 4'-azidocytidine (R1479), a drug previously identified to inhibit flaviviruses, against henipaviruses along with other representative members of the family Paramyxoviridae...
June 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28628616/therapeutic-administration-of-a-recombinant-human-monoclonal-antibody-reduces-the-severity-of-chikungunya-virus-disease-in-rhesus-macaques
#18
Rebecca Broeckel, Julie M Fox, Nicole Haese, Craig N Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois M A Colgin, Rebecca M Ducore, Anne D Lewis, Michael K Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara Carter, Gopal Sapparapau, James E Crowe, Michael S Diamond, Daniel N Streblow
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28628116/cadherin-composition-and-multicellular-aggregate-invasion-in-organotypic-models-of-epithelial-ovarian-cancer-intraperitoneal-metastasis
#19
Y Klymenko, O Kim, E Loughran, J Yang, R Lombard, M Alber, M S Stack
During epithelial ovarian cancer (EOC) progression, intraperitoneally disseminating tumor cells and multicellular aggregates (MCAs) present in ascites fluid adhere to the peritoneum and induce retraction of the peritoneal mesothelial monolayer prior to invasion of the collagen-rich submesothelial matrix and proliferation into macro-metastases. Clinical studies have shown heterogeneity among EOC metastatic units with respect to cadherin expression profiles and invasive behavior; however, the impact of distinct cadherin profiles on peritoneal anchoring of metastatic lesions remains poorly understood...
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28625919/c1q-tnf-related-protein-1-promotes-endothelial-barrier-dysfunction-under-disturbed-flow
#20
Zhu Hui Liu, Chang Li, Jia Wei Chen, Ying Shen, Jie Gao, Wei Feng Shen, Rui Yan Zhang, Xiao Qun Wang, Lin Lu
Endothelial hyper-permeability is a major determinant factor that contributes to the accelerated development of atherosclerotic lesions at hemodynamically disturbed sites. Previously, we showed that C1q/TNF related protein (CTRP) 1 promotes endothelium-leukocyte interactions and inflammatory responses in vascular cells. Here, we sought to investigate the role of CTRP1 in modulation of endothelial permeability under disturbed flow condition. By using en face staining of mouse aorta, we found CTRP1 expression was significantly increased in vascular endothelial cells under disturbed flow as compared to steady laminar flow...
June 15, 2017: Biochemical and Biophysical Research Communications
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