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"RSV vaccine"

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
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
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
Annette Fox, Kanta Subbarao, Patrick Reading
In this issue of Immunity, Goodwin et al. (2018) offer hope for an RSV vaccine for young infants by demonstrating that RSV infection in very young infants induces neutralizing antibodies that are close to the germline and have unusual epitope specificity.
February 20, 2018: Immunity
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
Lea Bayer, Jasmin Fertey, Sebastian Ulbert, Thomas Grunwald
Respiratory syncytial virus (RSV) is a pathogen causing severe lower respiratory tract disease in infants and the elderly. In spite of the great need for a vaccine against RSV, currently there is no licensed product on the market. A very early vaccine candidate developed in the 1960s based on formaldehyde inactivation (FI) turned out to instead enhance the disease. Our novel inactivation method applied low-energy electron irradiation (LEEI) to produce a killed RSV vaccine. LEEI yielded inactivated virus particles with a reproducible virus antigen conservation above 70%, while FI resulted in highly variable antigen conservation...
February 10, 2018: Vaccine
Jiri Beran, Jason D Lickliter, Tino F Schwarz, Casey Johnson, Laurence Chu, Joseph B Domachowske, Pierre Van Damme, Kanchanamala Withanage, Laurence A Fissette, Marie-Pierre David, Koen Maleux, Alexander C Schmidt, Marta Picciolato, Ilse Dieussaert
Background: Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost pre-existing neutralizing antibody titers, providing passive protection to newborns. Methods: Two observer-blind, controlled studies (RSV F-020 [NCT02360475], RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, non-pregnant 18-45-year-old women. Both studies used licensed Tdap vaccine as control...
February 1, 2018: Journal of Infectious Diseases
Eileen Goodwin, Morgan S A Gilman, Daniel Wrapp, Man Chen, Joan O Ngwuta, Syed M Moin, Patricia Bai, Arvind Sivasubramanian, Ruth I Connor, Peter F Wright, Barney S Graham, Jason S McLellan, Laura M Walker
Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated more than 450 RSV fusion glycoprotein (F)-specific antibodies from 7 RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F...
January 20, 2018: Immunity
Martin T Jepsen, Ramona Trebbien, Hanne Dorthe Emborg, Tyra G Krause, Kristian Schønning, Marianne Voldstedlund, Jens Nielsen, Thea K Fischer
For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual RSV-associated admissions in children < 5 years-old for the period of 2010-2015. We identified ca 2,500 RSV-associated hospitalisations annually amounting to total direct medical-costs of ca EUR 4.1 million per year...
January 2018: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
Xunyan Ye, Obinna P Iwuchukwu, Vasanthi Avadhanula, Letisha O Aideyan, Trevor J McBride, Laura L Ferlic-Stark, Kirtida D Patel, Felipe-Andres Piedra, Dimpy P Shah, Roy F Chemaly, Pedro A Piedra
Background: Most RSV vaccine candidates include fusion (F) protein in different conformations. Antigenic site II found in the different F conformations is the target of palivizumab, the only FDA approved monoclonal antibody (mAb). Serum palivizumab-like antibody (PLA) is a potential serologic correlate of immunity. The objective was to determine if different conformations of F protein in a palivizumab competitive antibody (PCA) assay affect the PLA concentrations. Methods: Four PCA assays were standardized using mAbs...
January 22, 2018: Journal of Infectious Diseases
Prasad S Kulkarni, Julia L Hurwitz, Eric A F Simões, Pedro A Piedra
Correlates of protection (CoPs) can play a significant role in vaccine development by assisting the selection of vaccine candidates for clinical trials, supporting clinical trial design and implementation, and simplifying tests of vaccine modifications. Because of this important role in vaccine development, it is essential that CoPs be defined by well-designed immunogenicity and efficacy studies, with attention paid to benefits and limitations. The respiratory syncytial virus (RSV) field is unique in that a great deal of information about the humoral response is available from basic research and clinical studies...
January 16, 2018: Viral Immunology
Xue-Yan Zheng, Yan-Jun Xu, Wei-Jie Guan, Li-Feng Lin
Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations...
January 11, 2018: Archives of Virology
Alexa C Robitaille, Elise Caron, Nicolas Zucchini, Espérance Mukawera, Damien Adam, Mélissa K Mariani, Anaïs Gélinas, Audray Fortin, Emmanuelle Brochiero, Nathalie Grandvaux
The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine...
December 12, 2017: Scientific Reports
Daiyin Tian, Michael B Battles, Syed M Moin, Man Chen, Kayvon Modjarrad, Azad Kumar, Masaru Kanekiyo, Kevin W Graepel, Noor M Taher, Anne L Hotard, Martin L Moore, Min Zhao, Zi-Zheng Zheng, Ning-Shao Xia, Jason S McLellan, Barney S Graham
A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different...
November 30, 2017: Nature Communications
Simon Van Herck, Lien Van Hoecke, Benoit Louage, Lien Lybaert, Ruben De Coen, Sabah Kasmi, Aaron P Esser-Kahn, Sunil A David, Lutz Nuhn, Bert Schepens, Xavier Saelens, Bruno G De Geest
The quest for new potent and safe adjuvants with which to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll-like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, amphotericin B (AmpB), a Food and Drug Administration approved antifungal drug, has recently been discovered to possess TLR-triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant...
December 13, 2017: Bioconjugate Chemistry
Hualin Li, Cheryl Callahan, Michael Citron, Zhiyun Wen, Sinoeun Touch, Morgan A Monslow, Kara S Cox, Daniel J DiStefano, Kalpit A Vora, Andrew Bett, Amy Espeseth
Respiratory syncytial virus (RSV) is a leading cause of serious lower respiratory tract disease in young children and older adults throughout the world. Prevention of severe RSV disease through active immunization is optimal but no RSV vaccine has been licensed so far. Immune mechanisms of protection against RSV infection in humans have not been fully established, thus a comprehensive characterization of virus-specific immune responses in a relevant animal model will be beneficial in defining correlates of protection...
2017: PloS One
Ralph A Tripp, Ultan F Power, Peter J M Openshaw, Lawrence M Kauvar
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) annually affecting >2 million children in the US <5 years old. In the elderly (>65 years old), RSV results in ∼175,000 hospitalizations annually in the US with worldwide incidence ∼34 million. There is no approved RSV vaccine and treatments are limited. Recently, a Phase 3 trial in the elderly using a recombinant RSV F protein vaccine failed to meet its efficacy objectives, namely prevention of moderate-to-severe RSV-associated LRTI and reduced incidence of acute respiratory disease...
November 8, 2017: Journal of Virology
Edward Goldstein, Hieu H Nguyen, Patrick Liu, Cecile Viboud, Claudia A Steiner, Colin J Worby, Marc Lipsitch
Background: While circulation of respiratory syncytial virus (RSV) results in high rates of hospitalization, particularly among young children and the elderly, little is known about the role of different age groups in propagating annual RSV epidemics. Methods: We evaluate the roles played by individuals in different age groups during RSV epidemics in the US between 2001-2012 using the previously defined relative risk (RR) statistic estimated for hospitalization data from the Healthcare Cost and Utilization Project (HCUP)...
November 3, 2017: Journal of Infectious Diseases
Jeong-Yoon Lee, Jun Chang
Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract disease in infants, young children, immunocompromised individuals, and the elderly. However, despite ongoing efforts to develop an RSV vaccine, there is still no authorized RSV vaccine for humans. Baculovirus has attracted attention as a vaccine vector because of its ability to induce a high level of humoral and cellular immunity, low cytotoxicity against various antigens, and biological safety for humans. In this study, we constructed a recombinant baculovirus- based vaccine expressing the M2 protein of RSV under the control of cytomegalovirus promoter (Bac_RSVM2) to induce CD8(+) T-cell responses which play an important role in viral clearance, and investigated its protective efficacy against RSV infection...
November 2017: Journal of Microbiology / the Microbiological Society of Korea
Ann-Muriel Steff, James Monroe, Kristian Friedrich, Sumana Chandramouli, Thi Lien-Anh Nguyen, Sai Tian, Sarah Vandepaer, Jean-François Toussaint, Andrea Carfi
Human respiratory syncytial virus (hRSV) is responsible for serious lower respiratory tract disease in infants and in older adults, and remains an important vaccine need. RSV fusion (F) glycoprotein is a key target for neutralizing antibodies. RSV F stabilized in its pre-fusion conformation (DS-Cav1 F) induces high neutralizing antibody titers in naïve animals, but it remains unknown to what extent pre-fusion F can boost pre-existing neutralizing responses in RSV seropositive adults. We here assess DS-Cav1 F immunogenicity in seropositive cattle pre-exposed to bovine RSV, a virus closely related to hRSV...
October 20, 2017: Nature Communications
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