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https://www.readbyqxmd.com/read/28413132/development-of-an-intradermal-dna-vaccine-delivery-strategy-to-achieve-single-dose-immunity-against-respiratory-syncytial-virus
#1
Trevor R F Smith, Katherine Schultheis, Matthew P Morrow, Kimberly A Kraynyak, Jay R McCoy, Kevin C Yim, Karuppiah Muthumani, Laurent Humeau, David B Weiner, Niranjan Y Sardesai, Kate E Broderick
Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon® DNA-based vaccine encoding engineered RSV-F antigen using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model...
April 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28410812/cd4-t-cells-support-establishment-of-rsv-specific-igg-and-iga-antibody-secreting-cells-in-the-upper-and-lower-murine-respiratory-tract-following-rsv-infection
#2
Robert E Sealy, Sherri L Surman, Julia L Hurwitz
The RSV vaccine field suffered a major set-back when children were vaccinated with a formalin-inactivated RSV vaccine (FI-RSV). Unexpectedly, the vaccinated children fared worse than unvaccinated children when they were naturally infected with RSV. Mouse models were then developed that implicated the CD4(+) T helper cell population as a contributor to adverse events. Today, the T cell is viewed with much caution in the RSV field, and its induction by vaccination is sometimes discouraged. Here we re-emphasize the beneficial role of the CD4(+) T cell...
May 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28404847/characterization-of-pre-f-gcn4t-a-modified-human-respiratory-syncytial-virus-fusion-protein-stabilized-in-a-non-cleaved-pre-fusion-conformation
#3
Normand Blais, Martin Gagné, Yoshitomo Hamuro, Patrick Rheault, Martine Boyer, Ann-Muriel Steff, Guy Baudoux, Vincent Dewar, Josée Demers, Jean-Louis Ruelle, Denis Martin
Human respiratory syncytial virus (hRSV) fusion protein (F) is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from pre- (pre-F) to post-fusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state may be a superior target for neutralizing antibodies than post-F. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28302410/meeting-report-who-consultation-on-respiratory-syncytial-virus-rsv-vaccine-development-geneva-25-26-april-2016
#4
Birgitte K Giersing, Ruth A Karron, Johan Vekemans, David C Kaslow, Vasee S Moorthy
Respiratory syncytial virus (RSV) is a leading viral cause of respiratory morbidity and mortality in infants and young children worldwide. Low and middle income countries (LMICs) account for approximately 99% of the global mortality estimates in this population, with up to 200,000 RSV deaths per year. The vaccine product development pipeline is diverse with the most advanced clinical candidate currently in phase III efficacy testing in pregnant women. In addition, a long-acting RSV-neutralizing monoclonal antibody (mAb) to be administered at birth to prevent serious RSV-related respiratory disease is in late stage clinical development, as are additional conventional mAb for use in high-risk infants...
March 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28298602/a-single-dose-recombinant-piv5-expressing-respiratory-syncytial-virus-f-and-g-proteins-protected-cotton-rats-and-african-green-monkeys-from-rsv-challenge
#5
Dai Wang, Shannon Phan, Daniel J DiStefano, Michael P Citron, Cheryl L Callahan, Lani Indrawati, Sheri A Dubey, Gwendolyn J Heidecker, Dhanasekaran Govindarajan, Xiaoping Liang, Biao He, Amy S Espeseth
Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) proteins in the cotton rat and African green monkey models for their replication, immunogenicity and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275196/mutating-the-cx3c-motif-in-the-g-protein-should-make-a-live-respiratory-syncytial-virus-vaccine-safer-and-more-effective
#6
S Boyoglu-Barnum, S O Todd, J Meng, T R Barnum, T Chirkova, L M Haynes, S J Jadhao, R A Tripp, A G Oomens, M L Moore, L J Anderson
Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif ((182)CWAIC(186)) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine A(186) within the CX3C motif to CX4C ((182)CWAIAC(187)), known to block binding to CX3CR1, might decrease disease...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275186/cpg-in-combination-with-an-inhibitor-of-notch-signaling-suppresses-fi-rsv-enhanced-airway-hyperresponsiveness-and-inflammation-through-inhibiting-th17-memory-responses-and-promoting-tissue-resident-memory-cells-in-lungs
#7
Lei Zhang, Hongyong Li, Yan Hai, Wei Yin, Wenjian Li, Boyang Zheng, Xiaomin Du, Na Li, Zhengzheng Zhang, Yuqing Deng, Ruihong Zeng, Lin Wei
Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross-talk between TLR and Notch signaling pathways results in fine tuning of TLR-triggered innate inflammatory responses...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275185/broadly-reactive-anti-rsv-g-antibodies-from-exposed-individuals-effectively-inhibit-infection-of-primary-airway-epithelial-cells
#8
B Cortjens, E Yasuda, X Yu, K Wagner, Y B Claassen, A Q Bakker, J B M van Woensel, T Beaumont
Respiratory syncytial virus (RSV) causes severe respiratory disease in young children. Antibodies specific for the RSV prefusion F protein have guided RSV vaccine research and in human serum these antibodies attribute to >90% of the neutralization response, however detailed insight in the composition of the human B cell repertoire against RSV is still largely unknown. In order to study the B cell repertoire of 3 healthy donors for specificity against RSV, CD27(+) memory B cells were isolated and immortalized using BCL6 and Bcl-xL...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28262332/report-from-the-world-health-organization-s-third-product-development-for-vaccines-advisory-committee-pdvac-meeting-geneva-8-10th-june-2016
#9
Birgitte K Giersing, Johan Vekemans, Samantha Nava, David C Kaslow, Vasee Moorthy
The third meeting of WHO's Product Development for Vaccines Advisory Committee (PDVAC) was held in June 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. Since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase III trials of a respiratory syncytial virus (RSV) vaccine candidate has started in the elderly and pregnant women...
March 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28250126/respiratory-syncytial-virus-rsv-vaccine-vectored-by-a-stable-chimeric-and-replication-deficient-sendai-virus-protects-mice-without-inducing-enhanced-disease
#10
Marian Alexander Wiegand, Gianni Gori-Savellini, Claudia Gandolfo, Guido Papa, Christine Kaufmann, Eva Felder, Alessandro Ginori, Maria Giulia Disanto, Donatella Spina, Maria Grazia Cusi
Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known as a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. Exchanging the ectodomain of the SeV F protein with its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28243940/modulation-of-the-host-immune-response-by-respiratory-syncytial-virus-proteins
#11
REVIEW
Megan E Schmidt, Steven M Varga
Respiratory syncytial virus (RSV) causes severe respiratory disease in both the very young and the elderly. Nearly all individuals become infected in early childhood, and reinfections with the virus are common throughout life. Despite its clinical impact, there remains no licensed RSV vaccine. RSV infection in the respiratory tract induces an inflammatory response by the host to facilitate efficient clearance of the virus. However, the host immune response also contributes to the respiratory disease observed following an RSV infection...
March 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28226227/protective-and-harmful-immunity-to-rsv-infection
#12
Peter J M Openshaw, Chris Chiu, Fiona J Culley, Cecilia Johansson
Respiratory syncytial virus (RSV) is an exceptional mucosal pathogen. It specializes in infection of the ciliated respiratory epithelium, causing disease of variable severity with little or no direct systemic effects. It infects virtually all children by the age of three years and then repeatedly infects throughout life; this it does despite relatively slight variations in antigenicity, apparently by inducing selective immunological amnesia. Inappropriate or dysregulated responses to RSV can be pathogenic, causing disease-enhancing inflammation that contributes to short- and long-term effects...
February 6, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28182741/etiology-of-severe-pneumonia-in-ecuadorian-children
#13
Sivani Jonnalagadda, Oswaldo Rodríguez, Bertha Estrella, Lora L Sabin, Fernando Sempértegui, Davidson H Hamer
BACKGROUND: In Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador. METHODS: This observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2-59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction...
2017: PloS One
https://www.readbyqxmd.com/read/28148790/immunization-with-low-doses-of-recombinant-postfusion-or-prefusion-respiratory-syncytial-virus-f-primes-for-vaccine-enhanced-disease-in-the-cotton-rat-model-independently-of-the-presence-of-a-th1-biasing-gla-se-or-th2-biasing-alum-adjuvant
#14
Kirsten Schneider-Ohrum, Corinne Cayatte, Angie Snell Bennett, Gaurav Manohar Rajani, Patrick McTamney, Krystal Nacel, Leigh Hostetler, Lily Cheng, Kuishu Ren, Terrence O'Day, Gregory A Prince, Michael P McCarthy
Respiratory syncytial virus (RSV) infection of children previously immunized with a nonlive, formalin-inactivated (FI)-RSV vaccine has been associated with serious enhanced respiratory disease (ERD). Consequently, detailed studies of potential ERD are a critical step in the development of nonlive RSV vaccines targeting RSV-naive children and infants. The fusion glycoprotein (F) of RSV in either its postfusion (post-F) or prefusion (pre-F) conformation is a target for neutralizing antibodies and therefore an attractive antigen candidate for a pediatric RSV subunit vaccine...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28134924/a-novel-pre-fusion-conformation-specific-neutralizing-epitope-on-the-respiratory-syncytial-virus-fusion-protein
#15
Jarrod J Mousa, Nurgun Kose, Pranathi Matta, Pavlo Gilchuk, James E Crowe
Respiratory syncytial virus (RSV) remains a major human pathogen, infecting the majority of infants before age two and causing re-infection throughout life. Despite decades of RSV research, there is no licensed RSV vaccine. Most candidate vaccines studied to date have incorporated the RSV fusion (F) surface glycoprotein, because the sequence of F is highly conserved among strains of RSV. To better define the human B cell response to RSV F, we isolated from a single donor 13 new neutralizing human monoclonal antibodies (mAbs) that recognize the RSV F protein in the pre-fusion conformation...
January 30, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28129031/virus-like-particle-vaccines-containing-f-or-f-and-g-proteins-confer-protection-against-respiratory-syncytial-virus-without-pulmonary-inflammation-in-cotton-rats
#16
Hye Suk Hwang, Ki-Hye Kim, Youri Lee, Young-Tae Lee, Eun-Ju Ko, SooJin Park, Jong Seok Lee, Byung-Cheol Lee, Young-Man Kwon, Martin L Moore, Sang-Moo Kang
Vaccine-enhanced disease has been a major obstacle in developing a safe vaccine against respiratory syncytial virus (RSV). This study demonstrates the immunogenicity, efficacy, and safety of virus-like particle (VLP) vaccines containing RSV F (F VLP), G (G VLP), or F and G proteins (FG VLP) in cotton rats. RSV specific antibodies were effectively induced by vaccination of cotton rats with F VLP or FG VLP vaccines. After challenge, lung RSV clearance was observed with RSV F, G, FG VLP, and formalin inactivated RSV (FI-RSV) vaccines...
January 27, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28111638/rapid-profiling-of-rsv-antibody-repertoires-from-the-memory-b-cells-of-naturally-infected-adult-donors
#17
Morgan S A Gilman, Carlos A Castellanos, Man Chen, Joan O Ngwuta, Eileen Goodwin, Syed M Moin, Vicente Mas, José A Melero, Peter F Wright, Barney S Graham, Jason S McLellan, Laura M Walker
Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in young children and the elderly. There are currently no licensed RSV vaccines, and passive prophylaxis with the monoclonal antibody palivizumab is restricted to high-risk infants in part due to its modest efficacy. Although it is widely agreed that an effective RSV vaccine will require the induction of a potent neutralizing antibody response against the RSV fusion (F) glycoprotein, little is known about the specificities and functional activities of RSV F-specific antibodies induced by natural infection...
December 16, 2016: Science Immunology
https://www.readbyqxmd.com/read/28092107/rsv-associated-hospitalizations-in-children-in-karachi-pakistan-implications-for-vaccine-prevention-strategies
#18
Asad Ali, Mohammad Tahir Yousafzai, Rabbia Waris, Fatima Jafri, Fatima Aziz, Imran Naeem Abbasi, Anita Zaidi
Major progress is being made in vaccines against Respiratory Syncytial Virus (RSV), with multiple vaccine candidates currently in the clinical phase of development. Making an investment case for public sector financing of RSV vaccine will require estimation of burden, cost-effectiveness, and impact. The aim of this study is to determine the proportion, age distribution and clinical spectrum of RSV associated hospitalizations in children in Karachi, Pakistan. A three years prospective study was conducted at the Aga Khan University Hospital in Karachi, a city of 20 million in south Pakistan, from August 2009 to June 2012...
January 16, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28058797/estimating-the-burden-of-respiratory-syncytial-virus-rsv-on-respiratory-hospital-admissions-in-children-less-than-five-years-of-age-in-england-2007-2012
#19
Rachel Melanie Reeves, Pia Hardelid, Ruth Gilbert, Fiona Warburton, Joanna Ellis, Richard G Pebody
BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of hospital admission in young children. With several RSV vaccines candidates undergoing clinical trials, recent estimates of RSV burden are required to provide a baseline for vaccine impact studies. OBJECTIVES: To estimate the number of RSV-associated hospital admissions in children aged <5 years in England over a 5-year period from 2007 using ecological time series modelling of national hospital administrative data...
March 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28049853/genetic-stability-of-genome-scale-deoptimized-rna-virus-vaccine-candidates-under-selective-pressure
#20
Cyril Le Nouën, Thomas McCarty, Michael Brown, Melissa Laird Smith, Roberto Lleras, Michael A Dolan, Masfique Mehedi, Lijuan Yang, Cindy Luongo, Bo Liang, Shirin Munir, Joshua M DiNapoli, Steffen Mueller, Eckard Wimmer, Peter L Collins, Ursula J Buchholz
Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. Codon pair deoptimized (CPD) versions of RSV were attenuated and temperature-sensitive...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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