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https://www.readbyqxmd.com/read/29048990/title-site-specific-glycosylation-profile-of-influenza-a-h1n1-hemagglutinin-through-tandem-mass-spectrometry
#1
Esteban Cruz, Joel Cain, Ben Crossett, Veysel Kayser
The study of influenza virus evolution in humans has revealed a significant role of glycosylation profile alterations in the viral glycoproteins - hemagglutinin (HA) and neuraminidase (NA), in the emergence of both seasonal and pandemic strains. Viral antigenic drift can modify the number and location of glycosylation sites, altering a wide range of biological activities and the antigenic properties of the strain. In view of the key role of glycans in determining antigenicity, elucidating the glycosylation profiles of influenza strains is a requirement towards the development of improved vaccines...
October 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29046448/in-vitro-neutralization-is-not-predictive-of-prophylactic-efficacy-of-broadly-neutralizing-monoclonal-antibodies-cr6261-and-cr9114-against-lethal-h2-influenza-virus-challenge-in-mice
#2
Troy C Sutton, Elaine W Lamirande, Kevin W Bock, Ian N Moore, Wouter Koudstaal, Muniza Rehman, Gerrit Jan Weverling, Jaap Goudsmit, Kanta Subbarao
Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused previous pandemics. H2 influenza viruses represent a pandemic threat due to continued circulation in wild birds and limited immunity in the human population. In the event of a pandemic, anti-viral agents are the mainstay for treatment, but broadly neutralizing antibodies (bNAbs) may be a viable alternative for short-term prophylaxis or treatment. The hemagglutinin stem binding bNAbs CR6261 and CR9114 have been shown to protect mice from severe disease following challenge with H1N1 and H5N1, and H1N1, H3N2, and influenza B viruses, respectively...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29034314/targeting-an-oncolytic-influenza-a-virus-to-tumor-tissue-by-elastase
#3
Irina Kuznetsova, Tobias Arnold, Thomas Aschacher, Cornelia Schwager, Balazs Hegedus, Tamas Garay, Marina Stukova, Maria Pisareva, Stephan Pleschka, Michael Bergmann, Andrej Egorov
Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29023601/adenovirus-vector-based-multi-epitope-vaccine-provides-partial-protection-against-h5-h7-and-h9-avian-influenza-viruses
#4
Ahmed O Hassan, Omar Amen, Ekramy E Sayedahmed, Sai V Vemula, Samuel Amoah, Ian York, Shivaprakash Gangappa, Suryaprakash Sambhara, Suresh K Mittal
The emergence of H5, H7, and H9 avian influenza virus subtypes in humans reveals their pandemic potential. Although human-to-human transmission has been limited, the genetic reassortment of the avian and human/porcine influenza viruses or mutations in some of the genes resulting in virus replication in the upper respiratory tract of humans could generate novel pandemic influenza viruses. Current vaccines do not provide cross protection against antigenically distinct strains of the H5, H7, and H9 influenza viruses...
2017: PloS One
https://www.readbyqxmd.com/read/29018438/antibody-immunity-induced-by-h7n9-avian-influenza-vaccines-evaluation-criteria-affecting-factors-and-implications-for-rational-vaccine-design
#5
Zenglei Hu, Xinan Jiao, Xiufan Liu
Severe H7N9 avian influenza virus (AIV) infections in humans have public health authorities around the world on high alert for the potential development of a human influenza pandemic. Currently, the newly-emerged highly pathogenic avian influenza A (H7N9) virus poses a dual challenge for public health and poultry industry. Numerous H7N9 vaccine candidates have been generated using various platforms. Immunization trials in animals and humans showed that H7N9 vaccines are apparently poorly immunogenic because they induced low hemagglutination inhibition and virus neutralizing antibody titers...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28993601/potency-of-an-inactivated-influenza-vaccine-prepared-from-a-duck-hokkaido-162-2013-h2n1-against-a-challenge-with-a-swine-missouri-2124514-2006-h2n3-in-mice
#6
Mizuho Suzuki, Masatoshi Okamatsu, Takahiro Hiono, Keita Matsuno, Yoshihiro Sakoda
H2N2 influenza virus caused a pandemic starting in 1957 but has not been detected in humans since 1968. Thus, most people are immunologically naive to viruses of the H2 subtype. In contrast, H2 influenza viruses are continually isolated from wild birds, and H2N3 viruses were isolated from pigs in 2006. H2 influenza viruses could cause a pandemic if re-introduced into humans. In the present study, a vaccine against H2 influenza was prepared as an effective control measure against a future human pandemic. A/duck/Hokkaido/162/2013 (H2N1), which showed broad antigenic cross-reactivity, was selected from the candidate H2 influenza viruses recently isolated from wild birds in Asian countries...
October 7, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28987424/strategies-to-obtain-multiple-recombinant-modified-vaccinia-ankara-vectors-applications-to-influenza-vaccines
#7
Andrea Barbieri, Maddalena Panigada, Elisa Soprana, Giuseppina Di Mario, Francesco Gubinelli, Valentina Bernasconi, Marta Recagni, Isabella Donatelli, Maria R Castrucci, Antonio G Siccardi
As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion ΔIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion ΔVI...
October 4, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28983731/viral-metagenomics-of-six-bat-species-in-close-contact-with-humans-in-southern-china
#8
Xue-Yan Zheng, Min Qiu, Wei-Jie Guan, Jin-Ming Li, Shao-Wei Chen, Ming-Ji Cheng, Shu-Ting Huo, Zhong Chen, Yi Wu, Li-Na Jiang, Qing Chen
Accumulating studies have shown that bats could harbor various important pathogenic viruses that could be transmitted to humans and other animals. Extensive metagenomic studies of different organs/tissues from bats have revealed a large number of novel or divergent viruses. To elucidate viral diversity and epidemiological and phylogenetic characteristics, six pooled fecal samples from bats were generated (based on bat species and geographic regions characteristic for virome analysis). These contained 500 fecal samples from six bat species, collected in four geographic regions...
October 5, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28978709/elicitation-of-protective-antibodies-against-a-broad-panel-of-h1n1-viruses-in-ferrets-pre-immune-to-historical-h1n1-influenza-viruses
#9
Donald M Carter, Christopher A Darby, Scott K Johnson, Michael A Carlock, Greg A Kirchenbaum, Joshua DiNapoli, Harold Kleanthous, Ted M Ross
Most pre-clinical animal studies test influenza vaccines in immunologically naïve animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have pre-existing immunity to influenza. In this study, novel, broadly-reactive influenza vaccine candidates were assessed in pre-immune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive HA antigens (COBRA) for H1N1 isolates...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28966056/a-potent-germline-like-human-monoclonal-antibody-targets-a-ph-sensitive-epitope-on-h7n9-influenza-hemagglutinin
#10
Fei Yu, He Song, Yanling Wu, So Young Chang, Lili Wang, Wei Li, Binbin Hong, Shuai Xia, Chunyu Wang, Surender Khurana, Yang Feng, Yanping Wang, Zhiwu Sun, Biao He, Dongni Hou, Jody Manischewitz, Lisa R King, Yuanlin Song, Ji-Young Min, Hana Golding, Xinhua Ji, Lu Lu, Shibo Jiang, Dimiter S Dimitrov, Tianlei Ying
The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28956760/genesis-and-spread-of-newly-emerged-highly-pathogenic-h7n9-avian-viruses-in-mainland-china
#11
Lei Yang, Wenfei Zhu, Xiyan Li, Minmei Chen, Jie Wu, Pengbo Yu, Shunxiang Qi, Yiwei Huang, Weixian Shi, Jie Dong, Xiang Zhao, Weijuan Huang, Zi Li, Xiaoxu Zeng, Hong Bo, Tao Chen, Wenbing Chen, Jia Liu, Ye Zhang, Zhenli Liang, Wei Shi, Yuelong Shu, Dayan Wang
The novel low pathogenic H7N9 avian influenza A viruses (LPAI H7N9) have caused a threat to public health for their high mortality and morbidity since their emergence in 2013. Recently, highly pathogenic variants of these H7N9 viruses (HPAI H7N9) have emerged and caused human infections and poultry outbreaks in Mainland China. However, it is still unclear how the HPAI H7N9 virus was generated and how it evolved and spread in China. Here, we show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze Delta Region and spread southward to the Pearl Delta Region, possibly through live poultry trades...
September 27, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28952435/virus-host-interactions-new-insights-and-advancements-in-drug-development-against-viral-pathogens
#12
Minakshi Prasad, Koushlesh Ranjan, Basanti Brar, Ikbal Shah, Upendra Lalmbe, J Manimegalai, Bhavya Vashisht, Madhusudan Gaury, Pawan Kumar, Sandip Kumar Khurana, Gaya Prasad, Jagveer Rawat, Vikas Yadav, Sunil Kumar, Rekha Rao
Viruses are the most devastating pathogens of almost all life forms including humans and animals. Viruses can replicate very fast and may affect any metabolic and physiological function of the host cell. Therefore, it has been a challenge to develop a universal and common treatment against viral pathogens, in contrast to bacterial pathogens. Virus-host interaction is a complex phenomenon and often is virus- and host cell-specific. Exciting new insights into the molecular pathogenesis and host-virus interactions have been gained over the past few decades...
September 24, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28947234/recombinant-hemagglutinin-proteins-formulated-in-a-novel-pelc-cpg-adjuvant-for-h7n9-subunit-vaccine-development
#13
Ting-Hsuan Chen, Ying-Yu Liu, Jia-Tsrong Jan, Ming-Hsi Huang, Maureen Spearman, Michael Butler, Suh-Chin Wu
Humans infected with H7N9 avian influenza viruses can result in severe pneumonia and acute respiratory syndrome with an approximately 40% mortality rate, and there is an urgent need to develop an effective vaccine to reduce its pandemic potential. In this study, we used a novel PELC/CpG adjuvant for recombinant H7HA (rH7HA) subunit vaccine development. After immunizing BALB/c mice intramuscularly, rH7HA proteins formulated in this adjuvant instead of an alum adjuvant elicited higher IgG, hemagglutination-inhibition, and virus neutralizing antibodies in sera; induced higher numbers of H7HA-specific IFN-γ-secreting T cells and antibody secreting cells in spleen; and provided improved protection against live virus challenges...
September 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28931922/efficacy-of-recombinant-measles-virus-expressing-highly-pathogenic-avian-influenza-virus-hpaiv-antigen-against-hpaiv-infection-in-monkeys
#14
Tomoko Fujiyuki, Ryo Horie, Misako Yoneda, Takeshi Kuraishi, Fumihiko Yasui, Hyun-Jeong Kwon, Keisuke Munekata, Fusako Ikeda, Miho Hoshi, Yuri Kiso, Mio Omi, Hiroki Sato, Hiroshi Kida, Shosaku Hattori, Michinori Kohara, Chieko Kai
Highly pathogenic avian influenza virus (HPAIV) is a serious threat not only to domestic fowls but also to humans. Vaccines inducing long-lasting immunity against HPAIV are required. In the present study, we generated recombinant measles virus (MV) expressing the hemagglutinin protein of HPAIV without the multibasic site necessary for its pathogenicity in chickens using the backbone of an MV vaccine strain (rMV-Ed-H5HA) or a wild-type MV-derived mutant (rMV-HL-Vko-H5HA). We examined protective efficacy of the candidate vaccines in the monkey infection model by the challenge with a HPAIV (H5N1)...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931689/vaccination-with-recombinant-parainfluenza-virus-5-expressing-neuraminidase-protects-against-homologous-and-heterologous-influenza-virus-challenge
#15
Alaina J Mooney, Jon D Gabbard, Zhuo Li, Daniel A Dlugolenski, Scott K Johnson, Ralph A Tripp, Biao He, S Mark Tompkins
Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) along with other emerging influenzas continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enables evasion of virus-inhibiting antibody responses, resulting in vaccine failure...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931687/a-dna-vaccine-that-targets-hemagglutinin-to-antigen-presenting-cells-protects-mice-against-h7-influenza
#16
Tor Kristian Andersen, Fan Zhou, Rebecca Cox, Bjarne Bogen, Gunnveig Grødeland
Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we have constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1)...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28928215/influenza-virus-hemagglutinin-stalk-specific-antibodies-in-human-serum-are-a-surrogate-marker-for-in-vivo-protection-in-a-serum-transfer-mouse-challenge-model
#17
Henning Jacobsen, Madhusudan Rajendran, Angela Choi, Haakon Sjursen, Karl A Brokstad, Rebecca J Cox, Peter Palese, Florian Krammer, Raffael Nachbagauer
The immunogenicity of current influenza virus vaccines is assessed by measuring an increase of influenza virus-specific antibodies in a hemagglutination inhibition assay. This method exclusively measures antibodies against the hemagglutinin head domain. While this domain is immunodominant, it has been shown that hemagglutination inhibition titers do not always accurately predict protection from disease. In addition, several novel influenza virus vaccines that are currently under development do not target the hemagglutinin head domain, but rather more conserved sites, including the hemagglutinin stalk...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28928207/a-perfect-storm-increased-colonization-and-failure-of-vaccination-leads-to-severe-secondary-bacterial-infection-in-influenza-virus-infected-obese-mice
#18
Erik A Karlsson, Victoria A Meliopoulos, Nicholas C van de Velde, Lee-Ann van de Velde, Beth Mann, Geli Gao, Jason Rosch, Elaine Tuomanen, Jon McCullers, Peter Vogel, Stacey Schultz-Cherry
Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Streptococcus pneumoniae Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28912784/comparison-of-the-protective-efficacy-of-neutralizing-epitopes-of-2009-pandemic-h1n1-influenza-hemagglutinin
#19
Bo Peng, Na Peng, Yanan Zhang, Fenghua Zhang, Xuguang Li, Haiyan Chang, Fang Fang, Fuyan Wang, Fangguo Lu, Ze Chen
The 2009 H1N1 influenza (Pdm09) pandemic has been referred to as the first influenza pandemic of the twenty-first century. There is a marked difference in antigenicity between the pandemic H1N1 virus and past seasonal H1N1 viruses, which allowed the pandemic virus to spread rapidly in humans. Antibodies (Abs) against hemagglutinin (HA), especially neutralizing Abs against epitopes in the head of HA, play critical roles in defending the host against the virus. Some preexisting neutralizing Abs that recognize neutralizing epitopes of Pdm09 HA, thereby affording cross-protection, have been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28912070/recombinant-influenza-h7-hemagglutinin-containing-cfllc-minidomain-in-the-transmembrane-domain-showed-enhanced-cross-protection-in-mice
#20
Yang Wang, Yun Zhang, Jialing Wu, Ying Lin, Zhihui Wu, Ying Wei, Xiaona Wei, Jianru Qin, Chunyi Xue, George Dacai Liu, Yongchang Cao
Since February 2013, H7N9 influenza virus, causing human infections with high mortality in China, has been a potential pandemic threat. The H7N9 viruses are found to diverge into distinct genotypes as other influenza viruses; thus a vaccine that can provide sufficient cross-protection against different genotypes of H7N9 viruses is urgently needed. Our previous studies demonstrated that the HA-based structural design approach by introducing a CFLLC minidomain into transmembrane domain (TM) of H1, H5 or H9 hemagglutinin (HA) proteins by replacing with H3 subtype HA TM could enhance their cross-protection...
September 12, 2017: Virus Research
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