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https://www.readbyqxmd.com/read/29121080/respiratory-syncytial-virus-elicits-enriched-cd8-t-lymphocyte-responses-in-lung-compared-with-blood-in-african-green-monkeys
#1
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
#2
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
#3
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/29076066/recombinant-baculovirus-based-vaccine-expressing-m2-protein-induces-protective-cd8-t-cell-immunity-against-respiratory-syncytial-virus-infection
#4
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/29057917/pre-fusion-rsv-f-strongly-boosts-pre-fusion-specific-neutralizing-responses-in-cattle-pre-exposed-to-bovine-rsv
#5
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/29029260/an-adjuvanted-postfusion-f-protein-based-vaccine-did-not-prevent-respiratory-syncytial-virus-illness-in-older-adults
#6
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/29021918/protection-of-calves-by-a-prefusion-stabilized-bovine-rsv-f-vaccine
#7
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
https://www.readbyqxmd.com/read/28988544/molecular-and-clinical-characterization-of-human-respiratory-syncytial-virus-in-south-korea-between-2009-and-2014
#8
E Park, P H Park, J W Huh, H J Yun, H K Lee, M H Yoon, S Lee, G Ko
Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT-PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43·3%) belonged to the ON1 genotype, 66 (46·8%) were NA1 genotype, 3 (2·1%) were GA5 genotype, and 1 (0·7%) belonged to the GA1 genotype...
November 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28967522/potential-impact-of-a-maternal-vaccine-for-rsv-a-mathematical-modelling-study
#9
Alexandra B Hogan, Patricia T Campbell, Christopher C Blyth, Faye J Lim, Parveen Fathima, Stephanie Davis, Hannah C Moore, Kathryn Glass
Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity and one of the main causes of hospitalisation in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is undergoing phase 3 trials. We developed a compartmental age-structured model for RSV transmission, validated using linked laboratory-confirmed RSV hospitalisation records for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from such a program...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28942341/respiratory-syncytial-virus-hospitalization-in-middle-aged-and-older-adults
#10
Ryan E Malosh, Emily T Martin, Amy P Callear, Joshua G Petrie, Adam S Lauring, Lois Lamerato, Alicia M Fry, Jill Ferdinands, Brendan Flannery, Arnold S Monto
BACKGROUND: The importance of Respiratory Syncytial Virus (RSV) is increasingly recognized in hospitalized adults, but mainly in those ≥ 65 years. OBJECTIVES: We sought to describe the epidemiology and clinical severity of RSV compared to influenza in hospitalized adults ≥18 years. STUDY DESIGN: Adults hospitalized with acute respiratory illnesses (ARI) of ≤10days duration were prospectively enrolled from two Michigan hospitals during two influenza seasons...
September 7, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28933663/type-iii-hypersensitivity-reactions-to-a-b-cell-epitope-antigen-are-abrogated-using-a-depot-forming-vaccine-platform
#11
Lisa D MacDonald, Alecia MacKay, Valarmathy Kaliaperumal, Genevieve Weir, Andrea Penwell, Rajkannan Rajagopalan, Joanne M Langley, Scott Halperin, Marc Mansour, Marianne M Stanford
Peptide antigens are combined with an adjuvant in order to increase immunogenicity in vivo. The immunogenicity and safety of a RSV vaccine formulated in a novel oil-based platform, DepoVax™ (DPX), was compared to an alum formulation. A peptide B cell epitope derived from RSV small hydrophobic ectodomain (SHe) served as the antigen. Both vaccines induced SHe-specific antibodies after immunization of mice. A single dose of the DPX-based formulation resulted in anti-SHe titres for up to 20 weeks. Boosting with Alum-SHe, but not with DPX-SHe, led to unexpected clinical signs such as decreased activity, cyanosis and drop in body temperature in mice but not in rabbits...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28903503/identifying-gaps-in-respiratory-syncytial-virus-disease-epidemiology-in-the-united-states-prior-to-the-introduction-of-vaccines
#12
Lindsay Kim, Brian Rha, Jon S Abramson, Larry J Anderson, Carrie L Byington, Grace L Chen, John DeVincenzo, Kathryn M Edwards, Janet A Englund, Ann R Falsey, Marie R Griffin, Ruth A Karron, Karen G Martin, H Cody Meissner, Flor M Munoz, Andrew T Pavia, Pedro A Piedra, William Schaffner, Eric A F Simões, Rosalyn Singleton, H Keipp Talbot, Edward E Walsh, Jane R Zucker, Susan I Gerber
Respiratory syncytial virus (RSV) causes lower respiratory tract illness frequently. No effective antivirals or vaccines for RSV are approved for use in the United States; however, there are at least 50 vaccines and monoclonal antibody products in development, with those targeting older adults and pregnant women (to protect young infants) in phase 2 and 3 clinical trials. Unanswered questions regarding RSV epidemiology need to be identified and addressed prior to RSV vaccine introduction to guide the measurement of impact and future recommendations...
September 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28903080/transplacental-transfer-of-maternal-respiratory-syncytial-virus-rsv-antibody-and-protection-against-rsv-disease-in-infants-in-rural-nepal
#13
Helen Y Chu, James Tielsch, Joanne Katz, Amalia S Magaret, Subarna Khatry, Stephen C LeClerq, Laxman Shrestha, Jane Kuypers, Mark C Steinhoff, Janet A Englund
BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia in children. RSV-specific antibody (ab) protects infants from disease, and may be increased by a potential strategy of maternal RSV vaccination. OBJECTIVES: To describe the effect of RSV antibody on RSV infection risk in infants in a resource-limited setting. STUDY DESIGN: In a prospective study in Nepal, women were enrolled during pregnancy and maternal and infant cord blood were collected at birth...
October 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28894111/induction-of-high-titred-non-neutralising-antibodies-by-self-adjuvanting-peptide-epitopes-derived-from-the-respiratory-syncytial-virus-fusion-protein
#14
Noushin Jaberolansar, Keith J Chappell, Daniel Watterson, Imogen M Bermingham, Istvan Toth, Paul R Young, Mariusz Skwarczynski
Respiratory syncytial virus (RSV) causes severe lower respiratory tract illness in infants and young children. The significant morbidity and mortality rates associated with RSV infection make an effective RSV vaccine development a priority. Two neutralising antibody binding sites, Ø and II, located on the pre-fusion RSV F glycoprotein are prime candidates for epitope-focused vaccine design. We report on a vaccine strategy that utilises a lipid core peptide (LCP) delivery system with self-adjuvanting properties in conjunction with either the antigenic site Ø or II (B cell epitopes) along with PADRE as a T helper cell epitope...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881156/nucleic-acid-based-vaccines-targeting-respiratory-syncytial-virus-delivering-the-goods
#15
Trevor R F Smith, Katherine Schultheis, Kate E Broderick
Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen...
November 2, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28865676/determining-the-outcomes-of-interventions-to-prevent-respiratory-syncytial-virus-disease-in-children-what-to-measure
#16
REVIEW
Ruth A Karron, Heather J Zar
Respiratory syncytial virus (RSV) is the most common cause of viral acute lower respiratory tract illness (LRTI) in young children, and a major cause of hospital admissions and health-care utilisation globally. Substantial efforts have been made to develop RSV vaccines and vaccine-like monoclonal antibodies to prevent acute RSV LRTI. Prevention of acute disease could improve long-term lung health, with potential effects on wheezing, asthma, and chronic lung disease. This Personal View describes assessments that should be initiated during clinical trials and continued after licensure to fully evaluate the effect of RSV preventive interventions...
August 30, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28856681/reduced-activation-and-proliferation-of-human-lymphocytes-exposed-to-respiratory-syncytial-virus-compared-to-cells-exposed-to-influenza-virus
#17
Elisa H Fleming, Eliana E Ochoa, Joan E Nichols, M Kerry O'Banion, Alan R Salkind, Norbert J Roberts
Both respiratory syncytial virus (RSV) and influenza A virus (IAV) may infect human peripheral blood mononuclear leukocytes (PBMC) during the immune response to viral challenge as the cells are recruited to the respiratory tract. The current studies demonstrated differences in PBMC responses to the two viruses very early after exposure, including reduced fos protein and CD69 expression and IL-2 production by RSV-exposed T lymphocytes. Exposure to RSV resulted in reduced lymphocyte proliferation despite evidence of a virus-specific T lymphocyte frequency equivalent to that for influenza virus...
January 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/28854003/soluble-f-proteins-exacerbate-pulmonary-histopathology-after-vaccination-upon-respiratory-syncytial-virus-challenge-but-not-when-presented-on-virus-like-particles
#18
Youri Lee, Young-Tae Lee, Eun-Ju Ko, Ki-Hye Kim, Hye Suk Hwang, Soojin Park, Young-Man Kwon, Sang Moo Kang
Respiratory syncytial virus (RSV) fusion (F) protein is suggested to be a protective vaccine target although its efficacy and safety concerns remain not well understood. We investigated immunogenicity, efficacy, and safety of F proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited IgG2a antibody and T helper type 1 (Th1) immune responses whereas F protein induced IgG1 isotype and Th2 responses. Despite lung viral clearance after prime or prime-boost and then RSV challenge, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils...
November 2, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28846899/virus-like-particle-vaccine-primes-immune-responses-preventing-inactivated-virus-vaccine-enhanced-disease-against-respiratory-syncytial-virus
#19
Hye Suk Hwang, Young-Tae Lee, Ki-Hye Kim, Eun-Ju Ko, Youri Lee, Young-Man Kwon, Sang-Moo Kang
Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge...
November 2017: Virology
https://www.readbyqxmd.com/read/28825870/intranasal-immunization-with-a-single-dose-of-the-fusion-protein-formulated-with-a-combination-adjuvant-induces-long-term-protective-immunity-against-respiratory-syncytial-virus
#20
R Garg, L Latimer, V Gerdts, A Potter, S van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) is the most common cause of respiratory tract infections in both children and elderly people. In this study we evaluated the short- and long-term protective efficacy of a single intranasal (IN) immunization with a RSV vaccine formulation consisting of a codon-optimized fusion (F) protein formulated with poly(I:C), an innate defense regulator peptide and a polyphosphazene (ΔF/TriAdj). This vaccine induced strong systemic and local immune responses, including RSV F-specific IgG1 and IgG2a, SIgA and virus neutralizing antibodies in mice...
August 21, 2017: Human Vaccines & Immunotherapeutics
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