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2018 Article - "Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children" (limited access)
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. During the following RSV season, participants were monitored for respiratory illness and pre- and post-RSV season serum antibodies.
Results: Vaccine virus was shed by 95% of vaccinees (median peak titers of 3.8 log10 PFU/mL by quantitative culture and 6.3 log10 copies/mL by PCR); 90% had ≥4-fold rise in serum neutralizing antibodies. Respiratory symptoms and fever were common in vaccine (95%) and placebo (78%). One vaccinee had grade 2 rhonchi concurrent with vaccine shedding, rhinovirus, and enterovirus. Eight of 19 vaccinees versus 2 of 9 placebo recipients had substantially increased RSV antibody titers after the RSV season without medically attended RSV disease, indicating anamnestic vaccine responses to wild-type RSV without significant illness.
Conclusion: LIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion.
Kit used: FTD FTD Respiratory pathogens 21
2018 Article - "Adenovirus types associated with severe respiratory diseases: A retrospective 4-year study in Kuwait" (limited access)
Summary: Human adenovirus (HAdV) infection can result in a severe respiratory disease. The aim of this study was to identify HAdV types detected in patients hospitalized for severe respiratory illness. The study population consisted of 743 patients with severe respiratory disease admitted to four major hospitals in Kuwait between January 2013 and December 2016. Respiratory specimens were retrospectively screened for 20 respiratory viruses by real-time PCR. The HAdV hexon gene was amplified and directly sequenced, and HAdV types were identified by performing Bayesian phylogenetic analysis. HAdV DNA was detected in 27 (3.6%) patients, with peaks in November and March. Most patients were infants and young children suffering from pneumonia or acute bronchiolitis. The detected HAdV types were C1, C2, C5, B3, and B7. Clusters of HAdV C1, C2, and C5 were observed with high posterior probability. All patients infected with HAdV C5 and 50% of patients infected with HAdV C2 or B7 were admitted to the intensive care unit (ICU). Co-infection with other viruses was detected in 44.4% of patients. The most common co-infecting virus was rhinovirus (HRV). HAdV/HRV co-infection was detected in two children who presumably developed disseminated HAdV infection and died. This is the first report describing the circulation of HAdV types associated with severe outcomes in Kuwait. These findings highlight the need for a national surveillance system to monitor changes in predominant HAdV types and increased numbers of severe respiratory infections.
Kit used: FTD Respiratory pathogens 21
2018 Article - "Clinical characteristics of influenza virus-induced lower respiratory infection during the 2015 to 2016 season" (limited access)
Background Influenza A(H1N1)pdm09 virus infections often manifest severe respiratory symptoms, particularly in patients with a past history of allergic disease. Most of these findings were reported during the 2009 pandemic. The purpose of this study was to detail the clinical characteristics of influenza virus-induced lower respiratory infection (LRI) during the A(H1N1)pdm09-predominant 2015–2016 season. Methods We retrospectively reviewed the clinical characteristics of influenza-induced LRI cases in children admitted to a tertiary children's hospital. Molecular diagnostic evaluation was performed on samples obtained from the most severe cases. Results We identified 66 patients with influenza-associated hospitalization and included 21 patients with influenza virus-induced LRI for analyses. Twelve patients (57%) were admitted to the pediatric intensive care unit, seven (33%) required mechanical ventilation, and three (14%) required extracorporeal membrane oxygenation. Plastic bronchitis (PB) was identified in six patients (29%), among whom a past medical history of asthma or food allergy were noted in all six patients. A past history of allergic disease was more common among patients with, than among those without, PB (p = 0.009). A(H1N1)pdm09 was detected from all the PB cases, and phylogenetic analyses of the hemagglutinin and neuraminidase genes demonstrated that this virus belonged to subclades 6B.1 and 6B.2. In the six PB cases, we found one patient with H275Y mutation in neuraminidase. Conclusion Allergic disease was a risk factor for developing PB due to influenza A(H1N1)pdm09 infection during the 2015–16 season.
Kit used: FTD Respiratory pathogens 21