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Respiratory Syncytial Virus vaccine

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https://www.readbyqxmd.com/read/29142300/structure-and-immunogenicity-of-pre-fusion-stabilized-human-metapneumovirus-f-glycoprotein
#1
Michael B Battles, Vicente Más, Eduardo Olmedillas, Olga Cano, Mónica Vázquez, Laura Rodríguez, José A Melero, Jason S McLellan
Human metapneumovirus (hMPV) is a frequent cause of bronchiolitis in young children. Its F glycoprotein mediates virus-cell membrane fusion and is the primary target of neutralizing antibodies. The inability to produce recombinant hMPV F glycoprotein in the metastable pre-fusion conformation has hindered structural and immunological studies. Here, we engineer a pre-fusion-stabilized hMPV F ectodomain and determine its crystal structure to 2.6 Å resolution. This structure reveals molecular determinants of strain-dependent acid-induced fusion, as well as insights into refolding from pre- to post-fusion conformations...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29131713/vaccines-we-need-but-don-t-have
#2
Stanley A Plotkin
Vaccinations have had tremendous success in the 20th century. However, in the 21st century, we are facing complex immunological issues in relation to controlling underlying infectious diseases. Therefore, new technologies are needed to develop vaccines against infectious diseases like respiratory syncytial virus, human immunodeficiency virus, and cytomegalovirus. In addition, recent emerging infections have taught us that we must prepare preventative measures in advance using our scientific abilities.
November 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29121080/respiratory-syncytial-virus-elicits-enriched-cd8-t-lymphocyte-responses-in-lung-compared-with-blood-in-african-green-monkeys
#3
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
https://www.readbyqxmd.com/read/29118126/respiratory-syncytial-virus-rsv-targeting-the-g-protein-provides-a-new-approach-for-an-old-problem
#4
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
https://www.readbyqxmd.com/read/29112722/on-the-relative-role-of-different-age-groups-during-epidemics-associated-with-respiratory-syncytial-virus
#5
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
https://www.readbyqxmd.com/read/29109465/evidence-for-human-streptococcus-pneumoniae-in-wild-and-captive-chimpanzees-a-potential-threat-to-wild-populations
#6
Sophie Köndgen, Sebastien Calvignac-Spencer, Kim Grützmacher, Verena Keil, Kerstin Mätz-Rensing, Kathrin Nowak, Sonja Metzger, John Kiyang, Antina Lübke Becker, Tobias Deschner, Roman M Wittig, Felix Lankester, Fabian H Leendertz
Habituation of wild great apes for tourism and research has had a significant positive effect on the conservation of these species. However, risks associated with such activities have been identified, specifically the transmission of human respiratory viruses to wild great apes, causing high morbidity and, occasionally, mortality. Here, we investigate the source of bacterial-viral co-infections in wild and captive chimpanzee communities in the course of several respiratory disease outbreaks. Molecular analyses showed that human respiratory syncytial viruses (HRSV) and human metapneumoviruses (HMPV) were involved in the etiology of the disease...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107745/respiratory-syncytial-virus-induces-nrf2-degradation-through-a-promyelocytic-leukemia-protein-ring-finger-protein-4-dependent-pathway
#7
Narayana Komaravelli, Maria Ansar, Roberto P Garofalo, Antonella Casola
Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway mucosa inflammation and cellular oxidative damage by triggering production of reactive oxygen species and by inhibiting at the same time expression of antioxidant enzymes, via degradation of the transcription factor NF-E2-related factor 2 (NRF2). RSV infection induces NRF2 deacetylation, ubiquitination, and degradation through a proteasome-dependent pathway...
October 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29102516/colocalization-of-intracellular-specific-iga-iciga-with-influenza-virus-in-patients-nasopharyngeal-aspirate-cells
#8
Tuck-Weng Kok, Maurizio Costabile, Gregory A Tannock, Peng Li
Inhibition of viral replication by icIgA antibodies has only been observed with in vitro studies using epithelial cell lines in transwell cultures. This effect appears to involve an interaction between polymeric immunoglobulin A (pIgA) and viral particles within an intracellular compartment, since IgA is transported across polarized cells. Polyclonal guinea pig antisera against purified influenza A virus and mouse antisera prepared against Influenza A/H3N2 hemagglutinin (HA0) cleavage loop peptides, were used in confocal fluorescence microscopy to show specific staining of wild-type influenza H1N1 and H3N2 viruses in clinical specimens...
November 2, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/29076073/dense-granule-protein-7-gra-7-of-toxoplasma-gondii-inhibits-viral-replication-in-vitro-and-in-vivo
#9
Prasanna Weeratunga, Thilina U B Herath, Tae-Hwan Kim, Hyun-Cheol Lee, Jae-Hoon Kim, Byeong-Hoon Lee, Eun-Seo Lee, Kiramage Chathuranga, W A Gayan Chathuranga, Chul-Su Yang, Jin Yeul Ma, Jong-Soo Lee
Dense granule protein-7 (GRA-7) is an excretory protein of Toxoplasma gondii. It is a potential serodiagnostic marker and vaccine candidate for toxoplasmosis. Previous reports demonstrated that GRA-7 induces innate immune responses in macrophages by interacting with TRAF6 via the MyD88-dependent pathway. In the present study, we evaluated the antiviral activity and induction of an antiviral state by GRA-7 both in vitro and in vivo. It was observed that GRA-7 markedly reduced the replication of vesicular stomatitis virus (VSV-GFP), influenza A virus (PR8-GFP), coxsackievirus (H3-GFP), herpes simplex virus (HSV-GFP), and adenovirus-GFP in epithelial (HEK293T/HeLa) and immune (RAW264...
November 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/29076066/recombinant-baculovirus-based-vaccine-expressing-m2-protein-induces-protective-cd8-t-cell-immunity-against-respiratory-syncytial-virus-infection
#10
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
https://www.readbyqxmd.com/read/29073183/adjuvants-and-the-vaccine-response-to-the-ds-cav1-stabilized-fusion-glycoprotein-of-respiratory-syncytial-virus
#11
Mallika Sastry, Baoshan Zhang, Man Chen, M Gordon Joyce, Wing-Pui Kong, Gwo-Yu Chuang, Kiyoon Ko, Azad Kumar, Chiara Silacci, Michelle Thom, Andres M Salazar, Davide Corti, Antonio Lanzavecchia, Geraldine Taylor, John R Mascola, Barney S Graham, Peter D Kwong
Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively...
2017: PloS One
https://www.readbyqxmd.com/read/29069315/the-impact-of-pneumococcal-vaccination-on-bacterial-and-viral-pneumonia-in-western-australian-children-record-linkage-cohort-study-of-469-589-births-1996-2012
#12
Parveen Fathima, Christopher C Blyth, Deborah Lehmann, Faye J Lim, Tasnim Abdalla, Nicholas de Klerk, Hannah C Moore
Background: Pneumococcal conjugate vaccine (PCV) was included in Australia's National Immunisation Program for all children from 2005. We assessed the impact of PCV on all-cause and pathogen-specific pneumonia hospitalisations in Western Australian (WA) children aged ≤16 years. Methods: All hospitalisations with pneumonia-related ICD-10AM diagnosis codes occurring in WA-born children (1996-2012) were linked to pathology records. Age-specific incidence rate ratios and temporal trends for all-cause and pathogen-specific pneumonia hospitalisations were calculated pre- and post-PCV introduction...
October 23, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29057917/pre-fusion-rsv-f-strongly-boosts-pre-fusion-specific-neutralizing-responses-in-cattle-pre-exposed-to-bovine-rsv
#13
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
https://www.readbyqxmd.com/read/29050992/the-impact-of-13-valent-pneumococcal-conjugate-vaccination-on-virus-associated-community-acquired-pneumonia-in-elderly
#14
Susanne M Huijts, Frank E J Coenjaerts, Marieke Bolkenbaas, Cornelis H van Werkhoven, Diederick E Grobbee, Marc J M Bonten
OBJECTIVES: Our objective was to evaluate whether vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) prevents the incidence of community-acquired pneumonia (CAP) caused by influenza (Influenza-Associated CAP, IA-CAP) or other respiratory viruses in elderly. METHODS: This analysis was part of the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA); a double blind, randomized, placebo-controlled trial in 84,496 immunocompetent individuals aged ≥65 years...
October 16, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29037975/modular-cell-based-platform-for-high-throughput-identification-of-compounds-that-inhibit-a-viral-interferon-antagonist-of-choice
#15
Andri Vasou, Christina Paulus, Janina Narloch, Zoe O Gage, Marie-Anne Rameix-Welti, Jean-François Eléouët, Michael Nevels, Richard E Randall, Catherine S Adamson
Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets...
October 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29036182/proteome-analysis-of-bronchoalveolar-lavage-from-calves-infected-with-bovine-respiratory-syncytial-virus-insights-in-pathogenesis-and-perspectives-for-new-treatments
#16
Sara Hägglund, Krister Blodörn, Katarina Näslund, Karin Vargmar, Sara Bergström Lind, Jia Mi, Mariluz Araínga, Sabine Riffault, Geraldine Taylor, John Pringle, Jean François Valarcher
Human and bovine respiratory syncytial viruses (HRSV/BRSV) are major causes of severe lower respiratory tract infections in children and calves, respectively. Shared epidemiological, clinical, pathological and genetic characteristics of these viruses make comparative research highly relevant. To characterise the host response against BRSV infection, bronchoalveolar lavage supernatant (BAL) from i) non-vaccinated, BRSV-infected ii) vaccinated, BRSV-infected and iii) non-infected calves was analysed by tandem mass spectrometry...
2017: PloS One
https://www.readbyqxmd.com/read/29029260/an-adjuvanted-postfusion-f-protein-based-vaccine-did-not-prevent-respiratory-syncytial-virus-illness-in-older-adults
#17
Judith Falloon, Jing Yu, Mark T Esser, Tonya Villafana, Li Yu, Filip Dubovsky, Therese Takas, Myron J Levin, Ann R Falsey
Background: Respiratory syncytial virus (RSV) is an important cause of illness in older adults. This study assessed efficacy of a vaccine for prevention of RSV-associated acute respiratory illness (RSV-ARI), defined by specified symptoms with virologic confirmation. Methods: This phase 2b study evaluated RSV postfusion F protein (120 µg) with glucopyranosyl lipid adjuvant (5 µg) in 2% stable emulsion. Subjects aged ≥60 years were randomized 1:1 to vaccine or placebo (all received influenza vaccine)...
September 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29029125/vaccine-prevention-of-respiratory-syncytial-virus-in-older-adults-the-work-continues
#18
Joanne M Langley
No abstract text is available yet for this article.
September 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29028839/interaction-of-the-human-respiratory-syncytial-virus-matrix-protein-with-cellular-adaptor-protein-complex-3-plays-a-critical-role-in-trafficking
#19
Casey Ward, Maciej Maselko, Christopher Lupfer, Meagan Prescott, Manoj K Pastey
Human Respiratory Syncytial Virus (HRSV) is a leading cause of bronchopneumonia in infants and the elderly. To date, knowledge of viral and host protein interactions within HRSV is limited and are critical areas of research. Here, we show that HRSV Matrix (M) protein interacts with the cellular adaptor protein complex 3 specifically via its medium subunit (AP-3Mu3A). This novel protein-protein interaction was first detected via yeast-two hybrid screen and was further confirmed in a mammalian system by immunofluorescence colocalization and co-immunoprecipitation...
2017: PloS One
https://www.readbyqxmd.com/read/29021918/protection-of-calves-by-a-prefusion-stabilized-bovine-rsv-f-vaccine
#20
Baoshan Zhang, Lei Chen, Chiara Silacci, Michelle Thom, Jeffrey C Boyington, Aliaksandr Druz, M Gordon Joyce, Efrain Guzman, Wing-Pui Kong, Yen-Ting Lai, Guillaume B E Stewart-Jones, Yaroslav Tsybovsky, Yongping Yang, Tongqing Zhou, Ulrich Baxa, John R Mascola, Davide Corti, Antonio Lanzavecchia, Geraldine Taylor, Peter D Kwong
Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated assessment of these vaccine candidates. Here, we use a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context...
March 8, 2017: NPJ Vaccines
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