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https://www.readbyqxmd.com/read/28624306/preclinical-assessment-of-safety-of-maternal-vaccination-against-respiratory-syncytial-virus-rsv-in-cotton-rats
#1
Jorge C G Blanco, Lioubov M Pletneva, Raymonde O Otoa, Mira C Patel, Stefanie N Vogel, Marina S Boukhvalova
Maternal immunization directed to control RSV infection in newborns and infants is an appealing vaccination strategy currently under development. In this work we have modeled maternal vaccination against RSV in cotton rats (CR) to answer two fundamental questions on maternal vaccine safety. We tested (i), whether a known, unsafe RSV vaccine (i.e., FI-RSV Lot 100 vaccine) induces vaccine enhanced disease in the presence of passively transferred, RSV maternal immunity, and (ii) whether the same FI-RSV vaccine could induce vaccine enhanced disease in CR litters when used to immunize their RSV-primed mothers...
June 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28574729/respiratory-syncytial-virus-prospects-for-new-and-emerging-therapeutics
#2
Patricia A Jorquera, Ralph A Tripp
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections (LRTI) in infants, the elderly, and the immunocompromised. Although the development of a RSV vaccine has been a priority for >50 years, there is still no vaccine available. Treatment of RSV LRTI has remained mostly supportive, i.e. hydration and oxygenation. Palivizumab and ribavirin are the only options currently available for prevention and treatment of RSV infection, but evidence suggests that they are not fully effective...
June 14, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28558308/age-predicts-cytokine-kinetics-and-innate-immune-cell-activation-following-intranasal-delivery-of-ifn%C3%AE-and-gm-csf-in-a-mouse-model-of-rsv-infection
#3
Katherine M Eichinger, Erin Resetar, Jacob Orend, Kacey Anderson, Kerry M Empey
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and is further associated with increased healthcare utilization and cost of care in the first years of life. Severe RSV disease during infancy has also been linked to the later development of allergic asthma, yet there remains no licensed RSV vaccine or effective treatment. Pre-clinical and clinical studies have shown that disease severity and development of allergic asthma are associated with differences in cytokine production...
May 27, 2017: Cytokine
https://www.readbyqxmd.com/read/28539444/improved-prefusion-stability-optimized-codon-usage-and-augmented-virion-packaging-enhance-the-immunogenicity-of-respiratory-syncytial-virus-rsv-fusion-protein-in-a-vectored-vaccine-candidate
#4
Bo Liang, Joan O Ngwuta, Sonja Surman, Barbora Kabatova, Xiang Liu, Matthias Lingemann, Xueqiao Liu, Lijuan Yang, Richard Herbert, Joanna Swerczek, Man Chen, Syed M Moin, Azad Kumar, Jason S McLellan, Peter D Kwong, Barney S Graham, Peter L Collins, Shirin Munir
Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but lacks a licensed vaccine or suitable antiviral drug. A live-attenuated chimeric bovine/human parainfluenza virus type-3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naïve children, rB/HPIV3 was well-tolerated but the immunogenicity of wildtype RSV F was unsatisfactory...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28525961/passive-and-active-immunization-against-respiratory-syncytial-virus-for-the-young-and-old
#5
Tonya Villafana, Judith Falloon, M Pamela Griffin, Qing Zhu, Mark T Esser
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants worldwide and also causes significant disease in the elderly. Despite 60 years of RSV research and vaccine development, there is only one approved medicine to prevent RSV infections. Palivizumab, a monoclonal antibody (mAb) against the RSV fusion (F) protein, is indicated for preterm infants and children at high-risk for RSV infections. It is an active time in RSV vaccine and mAb development with 14 vaccines and 2 mAbs currently being tested in clinical trials as of 13 February 2017...
July 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28508217/bac-based-recovery-of-recombinant-respiratory-syncytial-virus-rsv
#6
Christopher C Stobart, Anne L Hotard, Jia Meng, Martin L Moore
Respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand RNA virus, which causes lower respiratory tract infections and is a leading cause of mortality in young infants. There is no available RSV vaccine and currently administered prophylactic antibodies are limited to high-risk populations. Current efforts to develop vaccines include development of live-attenuated RSV candidates. We describe here methods for preparation and recovery of recombinant RSV using an efficient bacterial artificial chromosome (BAC)-based system, expansion and plaque purification of recovered virus, and generation of master and working stocks...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28500974/ongoing-developments-in-rsv-prophylaxis-a-clinician-s-analysis
#7
REVIEW
Fariba Rezaee, Debra T Linfield, Terri J Harford, Giovanni Piedimonte
Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. Furthermore, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma...
May 10, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28476625/a-multi-laboratory-study-of-diverse-rsv-neutralization-assays-indicates-feasibility-for-harmonization-with-an-international-standard
#8
Nancy Hosken, Brian Plikaytis, Carrie Trujillo, Kutub Mahmood, Deborah Higgins
A current barrier to the standardized evaluation of respiratory syncytial virus (RSV) vaccine candidates is the wide variety of virus neutralization assay formats currently in use for assessing immunogenicity. Assay formats vary widely in labor intensiveness, duration, and sample throughput. Furthermore, the cell lines and virus strains used are not consistent among formats. The purpose of this multi-laboratory study was to assess the variability across a diverse array of assay formats that quantitate RSV neutralizing antibodies...
May 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28469033/a-highly-potent-extended-half-life-antibody-as-a-potential-rsv-vaccine-surrogate-for-all-infants
#9
Qing Zhu, Jason S McLellan, Nicole L Kallewaard, Nancy D Ulbrandt, Susan Palaszynski, Jing Zhang, Brian Moldt, Anis Khan, Catherine Svabek, Josephine M McAuliffe, Daniel Wrapp, Nita K Patel, Kimberly E Cook, Bettina W M Richter, Patricia C Ryan, Andy Q Yuan, JoAnn A Suzich
Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose...
May 3, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28413132/development-of-an-intradermal-dna-vaccine-delivery-strategy-to-achieve-single-dose-immunity-against-respiratory-syncytial-virus
#10
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
#11
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
#12
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
#13
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-parainfluenza-virus-5-vectored-vaccine-expressing-respiratory-syncytial-virus-rsv-f-or-g-protein-protected-cotton-rats-and-african-green-monkeys-from-rsv-challenge
#14
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) protein 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...
June 1, 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
#15
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, mutating it to CX4C ((182)CWAIAC(187)), which is known to block binding to CX3CR1, might decrease disease...
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275186/cpg-in-combination-with-an-inhibitor-of-notch-signaling-suppresses-formalin-inactivated-respiratory-syncytial-virus-enhanced-airway-hyperresponsiveness-and-inflammation-by-inhibiting-th17-memory-responses-and-promoting-tissue-resident-memory-cells-in-lungs
#16
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...
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275185/broadly-reactive-anti-respiratory-syncytial-virus-g-antibodies-from-exposed-individuals-effectively-inhibit-infection-of-primary-airway-epithelial-cells
#17
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 contribute to >90% of the neutralization response; however, detailed insight into the composition of the human B cell repertoire against RSV is still largely unknown. In order to study the B cell repertoire of three healthy donors for specificity against RSV, CD27(+) memory B cells were isolated and immortalized using BCL6 and Bcl-xL...
May 15, 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
#18
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/a-respiratory-syncytial-virus-vaccine-vectored-by-a-stable-chimeric-and-replication-deficient-sendai-virus-protects-mice-without-inducing-enhanced-disease
#19
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 to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component...
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28243940/modulation-of-the-host-immune-response-by-respiratory-syncytial-virus-proteins
#20
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
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