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Respiratory Syncytial Virus vaccine

Stephanie Ascough, Suzanna Paterson, Christopher Chiu
Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived...
2018: Frontiers in Immunology
N Haber
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and young children. Reinfections are common throughout adult life with more severe presentations occurring in immunocompromised individuals, subjects with underlying high-risk cardiopulmonary diseases, and in the elderly. There is now a significant body of literature indicating that the impact of RSV in elderly adults is similar to that of non-pandemic influenza, both in the community and in nursing homes...
March 13, 2018: Médecine et Maladies Infectieuses
Edward E Walsh, Lu Wang, Ann R Falsey, Xing Qiu, Anthony Corbett, Jeanne Holden-Wiltse, Thomas J Mariani, David J Topham, Mary T Caserta
Background: Maternally derived serum antibody and viral load are thought to influence disease severity in primary Respiratory Syncytial Virus (RSV) infection. As part of the AsPIRES study of RSV pathogenesis we correlated various serum antibody concentrations and viral load with disease severity. Methods: Serum neutralizing titers and IgG to RSV F, Ga and Gb proteins, the CX3C region of G, and nasal viral load were measured in 139 full-term previously healthy infants with primary RSV infection and correlated with illness severity...
March 13, 2018: Journal of Infectious Diseases
Mira C Patel, Kari Ann Shirey, Marina S Boukhvalova, Stefanie N Vogel, Jorge C G Blanco
Host-derived "danger-associated molecular patterns" (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI...
March 13, 2018: MBio
Stanislav O Fedechkin, Natasha L George, Jacob T Wolff, Lawrence M Kauvar, Rebecca M DuBois
Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in young children and the elderly. The viral envelope G glycoprotein contributes to pathogenesis through its roles in host cell attachment and modulation of host immunity. Although the G glycoprotein is a target of protective RSV-neutralizing antibodies, its development as a vaccine antigen has been hindered by its heterogeneous glycosylation and sequence variability outside a conserved central domain (CCD)...
March 9, 2018: Science Immunology
Ursula J Buchholz, Coleen K Cunningham, Petronella Muresan, Devasena Gnanashanmugam, Paul Sato, George K Siberry, Vivian Rexroad, Megan Valentine, Charlotte Perlowski, Elizabeth Schappell, Bhagvinji Thumar, Cindy Luongo, Emily Barr, Mariam Aziz, Ram Yogev, Stephen A Spector, Peter L Collins, Elizabeth J McFarland, Ruth A Karron
Background: Respiratory syncytial virus (RSV) is the most important viral cause of severe respiratory illness in young children and lacks a vaccine. RSV cold-passage/stabilized 2 (RSVcps2) is a modification of a previously evaluated vaccine candidate in which 2 major attenuating mutations have been stabilized against deattenuation. Methods: RSV-seronegative 6-24-month-old children received an intranasal dose of 105.3 plaque-forming units (PFU) of RSVcps2 (n = 34) or placebo (n = 16) (International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1114 and companion protocol CIR285)...
March 2, 2018: Journal of Infectious Diseases
Fernando P Polack
No abstract text is available yet for this article.
March 2, 2018: Journal of Infectious Diseases
Elizabeth J McFarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Megan E Valentine, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, George K Siberry, Elizabeth Schappell, Emily Barr, Vivian Rexroad, Ram Yogev, Stephen A Spector, Mariam Aziz, Nehali Patel, Mikhaela Cielo, Cindy Luongo, Peter L Collins, Ursula J Buchholz
Background: Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication. Methods: RSV-seronegative children ages 6-24 months received a single intranasal dose of 105 plaque forming units (PFU) of LIDΔM2-2 (n = 20) or placebo (n = 9) (NCT02237209, NCT02040831). RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed...
March 2, 2018: Journal of Infectious Diseases
Harrison G Jones, Tina Ritschel, Gabriel Pascual, Just P J Brakenhoff, Elissa Keogh, Polina Furmanova-Hollenstein, Ellen Lanckacker, Jehangir S Wadia, Morgan S A Gilman, R Anthony Williamson, Dirk Roymans, Angélique B van 't Wout, Johannes P Langedijk, Jason S McLellan
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models...
March 6, 2018: PLoS Pathogens
Xiangxiang Shi, Jun Zheng, Tingting Yan
Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. Here, the RSV fusion (F) glycoprotein epitope FFL was redesigned based on its complex crystal structure with motavizumab, an mAb drug in development for the prevention of RSV infections, aiming to obtain therapeutic peptide vaccines with high affinity to induce RSV-specific neutralizing antibodies. Computational modeling and analysis found that only a small region covering the helix-turn-helix (HTH) motif of FFL can directly interact with motavizumab and confer stability and specificity to the complex system, while the rest of the epitope primarily serves as a structural scaffold that stabilizes the HTH conformation of motavizumab-binding site...
March 2, 2018: Journal of Molecular Modeling
Kamal Kant, Uma Ranjan Lal, Manik Ghosh
Background: To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. Objective: This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV...
January 2018: Pharmacognosy Magazine
Mireya Robledo-Aceves, María de Jesús Moreno-Peregrina, Fernando Velarde-Rivera, Elba Ascencio-Esparza, Francisco M Preciado-Figueroa, Miguela A Caniza, Griselda Escobedo-Melendez
Severe bronchiolitis is the most common reason for hospitalization among children younger than 2 years. This study analyzed the prevalence of community-acquired respiratory virus infection and the risk factors for hospitalization of Mexican children with severe bronchiolitis treated in an Emergency department.This retrospective study included 134 children 2 years or younger with severe viral bronchiolitis, and 134 healthy age-matched controls. The study period was September 2012 to January 2015. We determined the viral etiology and coinfections with multiple viruses and compared the risk factors detected in children with severe viral bronchiolitis with those in the control group...
March 2018: Medicine (Baltimore)
Helen T Groves, Leah Cuthbertson, Phillip James, Miriam F Moffatt, Michael J Cox, John S Tregoning
Alterations in the composition of the gut microbiota have profound effects on human health. Consequently, there is great interest in identifying, characterizing, and understanding factors that initiate these changes. Despite their high prevalence, studies have only recently begun to investigate how viral lung infections have an impact on the gut microbiota. There is also considerable interest in whether the gut microbiota could be manipulated during vaccination to improve efficacy. In this highly controlled study, we aimed to establish the effect of viral lung infection on gut microbiota composition and the gut environment using mouse models of common respiratory pathogens respiratory syncytial virus (RSV) and influenza virus...
2018: Frontiers in Immunology
Alisa Kachikis, Linda O Eckert, Janet Englund
Maternal immunization for prevention of morbidity and mortality of pregnant women and their neonates due to infectious diseases is ongoing worldwide. The complexity of vaccine research and development in this population is challenging. Not only do vaccines for pregnant women require evidence of immunogenicity, potency, stability, and limited reactogenicity, they must also provide efficacy in decreasing morbidity for the pregnant woman, her fetus, and the neonate, demonstrate safety or lack of evidence of harm, and offer benefit or potential benefit of vaccination during pregnancy...
February 23, 2018: Viral Immunology
Eric A F Simões, Louis Bont, Paolo Manzoni, Brigitte Fauroux, Bosco Paes, Josep Figueras-Aloy, Paul A Checchia, Xavier Carbonell-Estrany
INTRODUCTION: The REGAL (RSV Evidence - A Geographical Archive of the Literature) series has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This seventh and final publication covers the past, present and future approaches to the prevention and treatment of RSV infection among infants and children. METHODS: A systematic review was undertaken of publications between January 1, 1995 and December 31, 2017 across PubMed, Embase and The Cochrane Library...
February 22, 2018: Infectious Diseases and Therapy
Jarrod J Mousa, Elad Binshtein, Stacey Human, Rachel H Fong, Gabriela Alvarado, Benjamin J Doranz, Martin L Moore, Melanie D Ohi, James E Crowe
Respiratory syncytial virus (RSV) is a major human pathogen that infects the majority of children by two years of age. The RSV fusion (F) protein is a primary target of human antibodies, and it has several antigenic regions capable of inducing neutralizing antibodies. Antigenic site IV is preserved in both the pre-fusion and post-fusion conformations of RSV F. Antibodies to antigenic site IV have been described that bind and neutralize both RSV and human metapneumovirus (hMPV). To explore the diversity of binding modes at antigenic site IV, we generated a panel of four new human monoclonal antibodies (mAbs) and competition-binding suggested the mAbs bind at antigenic site IV...
February 2018: PLoS Pathogens
Mauricio T Caballero, Fernando P Polack
Respiratory syncytial virus (RSV), responsible for more than three million yearly hospitalizations and up to 118 000 deaths in children under 5 years, is the leading pulmonary cause of death for this age group that lacks a licensed vaccine. Ninety-nine percent of deaths due to the virus occur in developing countries. In-hospital RSV fatalities affect previously healthy term infants in association with bacterial sepsis, clinically significant pneumothoraxes and, to a lesser extent, comorbid conditions. Community deaths affect low-income children from socially vulnerable families and appear to be as frequent as inpatient fatalities...
February 20, 2018: Pediatric Pulmonology
M Gia Green, Natasha Petroff, Krista M D La Perle, Stefan Niewiesk
Eosinophils have been postulated to play a protective role against infection with respiratory syncytial virus (RSV), increase the severity of allergic asthma during respiratory viral infection, and drive vaccine-enhanced disease. To address these questions in the cotton rat model of RSV infection, we characterized cotton rat eosinophils by electron microscopy as well as by bronchoalveolar lavage and histology of lung sections. Using these methods, we demonstrated that eosinophils comprise approximately half of all cells in the bronchoalveolar lavage fluids from cotton rats...
February 1, 2018: Comparative Medicine
Matieyendou Didier Djagbare, Li Yu, Arun Parupudi, Jenny Sun, Melissa L Coughlin, Benjamin S Rush, Gautam Sanyal
The post-fusion form of Respiratory Syncytial Virus (RSV) fusion (F) protein has been used recently in clinical trials as a potential vaccine antigen with the objective of eliciting protective immune response against RSV. In this paper, in vitro antigenicity and in vivo immunogenicity of recombinant, soluble F protein of RSV (RSVsF) were evaluated by several assays. In Vitro Relative Potency (IVRP) of RSVsF was measured in a sandwich ELISA using two antibodies, each specific for epitope site A or C. Therefore, IVRP reflected the integrity of the antigen in terms of changes in antibody binding affinity of either or both of these sites...
February 15, 2018: Vaccine
Young J Lee, Jeong Y Lee, Yo H Jang, Sang-Uk Seo, Jun Chang, Baik L Seong
The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses...
2018: Frontiers in Microbiology
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