scholarly journals Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice

Author(s):  
Anneliese Ashhurst ◽  
Matt Johansen ◽  
Joshua Maxwell ◽  
Caroline Ashley ◽  
Anupriya Aggarwal ◽  
...  

Abstract Current vaccines against SARS-CoV-2 substantially reduce mortality, but protection against infection is less effective. Enhancing immunity in the respiratory tract, via mucosal vaccination, may provide protection against infection and minimise viral spread. We tested a novel subunit vaccine in mice, consisting of SARS-CoV-2 Spike protein with a TLR2-stimulating adjuvant, delivered to mice parenterally or mucosally. Both routes of vaccination induced substantial neutralising antibody (nAb) titres, however, mucosal vaccination uniquely generated anti-Spike IgA, increased nAb in the serum and airways, and increased lung CD4+ T-cell responses. TLR2 is expressed by respiratory epithelia and immune cells. Using TLR2 deficient chimeric mice, we determined that TLR2 expression in either compartment facilitated early innate responses to mucosal vaccination. By contrast, TLR2 on hematopoietic cells was essential for optimal lung-localised, antigen-specific responses. In a K18-hACE2 mice, vaccination provided complete protection against disease and sterilising lung immunity against SARS-CoV-2. These data support mucosal vaccination as a strategy to improve protection in the respiratory tract against SARS-CoV-2 and other respiratory viruses.

2020 ◽  
Vol 19 (2) ◽  
pp. 14-18
Author(s):  
E. V. Sharipova ◽  
I. V. Babachenko ◽  
M. A. Shcherbatyh

Long time the main pathogens associated with the development of community-acquired pneumonia were bacteria. However, in recent years in the Russian Federation, like all over the world, the view of the damage of lower respiratory tract changed, including a unique approach to community-acquired pneumonia as a bacterial infection, and respiratory viruses have become seen as a direct cause of lower respiratory tract damage, or as part of a viral-bacterial co-infection. These studies became possible since the widespread introduction of PCR techniques in the clinical setting, identification of respiratory viruses has increased and new microorganisms such, one as human bocavirus have been discovered. Objective: to study the features of respiratory tract damage in acute bocavirus infection in children of different ages. Materials and methods: A retrospective analysis of 97 medical hospital documentation of children with acute bocavirus infection, detected confirmed by PCR in nasopharyngeal aspirate. Results: In this work, it was shown that human bocavirus spread throughout the year with an increase in the incidence of clinically significant forms in the autumnwinter period, including during the period of an increase in the incidence of influenza. HBoV infection requiring hospitals is most significant in the first three years of life. In 74.2% of hospitalized children, bocavirus infection occurs with lower respiratory tract infections in the form of bronchitis — 77.8%, pneumonia — 28.9% and rarely bronchiolitis and is complicated by the development of respiratory failure in 28.9% of cases. Changes in the blood test are non-specific, and the level of C-reactive protein in children with various clinical manifestations of HBoV infection generally does not exceed 50 mg / l. An x-ray of the chest organs does not objectively reflect the existing volume and nature of the inflammatory process in the lungs.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rafik Dey ◽  
Melanie A. Folkins ◽  
Nicholas J. Ashbolt

AbstractHuman respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in children and immunocompromised adults worldwide. Here we report that amoebae-release respirable-sized vesicles containing high concentrations of infectious RSV that persisted for the duration of the experiment. Given the ubiquity of amoebae in moist environments, our results suggest that extracellular amoebal-vesicles could contribute to the environmental persistence of respiratory viruses, including potential resistance to disinfection processes and thereby offering novel pathways for viral dissemination and transmission.


2018 ◽  
Vol 69 (7) ◽  
pp. 1192-1197 ◽  
Author(s):  
Maddalena Peghin ◽  
Ibai Los-Arcos ◽  
Hans H Hirsch ◽  
Gemma Codina ◽  
Víctor Monforte ◽  
...  

Abstract Background The relationship between community-acquired respiratory viruses (CARVs) and chronic lung allograft dysfunction (CLAD) in lung transplant recipients is still controversial. Methods We performed a prospective cohort study (2009–2014) in all consecutive adult patients (≥18 years) undergoing lung transplantation in the Hospital Universitari Vall d’Hebron (Barcelona, Spain). We systematically collected nasopharyngeal swabs from asymptomatic patients during seasonal changes, from patients with upper respiratory tract infectious disease, lower respiratory tract infectious disease (LRTID), or acute rejection. Nasopharyngeal swabs were analyzed by multiplex polymerase chain reaction. Primary outcome was to evaluate the potential association of CARVs and development of CLAD. Time-dependent Cox regression models were performed to identify the independent risk factors for CLAD. Results Overall, 98 patients (67 bilateral lung transplant recipients; 63.3% male; mean age, 49.9 years) were included. Mean postoperative follow-up was 3.4 years (interquartile range [IQR], 2.5–4.0 years). Thirty-eight lung transplant recipients (38.8%) developed CLAD, in a median time of 20.4 months (IQR, 12–30.4 months). In time-controlled multivariate analysis, CARV-LRTID (hazard ratio [HR], 3.00 [95% confidence interval {CI}, 1.52–5.91]; P = .002), acute rejection (HR, 2.97 [95% CI, 1.51–5.83]; P = .002), and cytomegalovirus pneumonitis (HR, 3.76 [95% CI, 1.23–11.49]; P = .02) were independent risk factors associated with developing CLAD. Conclusions Lung transplant recipients with CARVs in the lower respiratory tract are at increased risk to develop CLAD.


Author(s):  
Chien-Yu Lin ◽  
David Hwang ◽  
Nan-Chang Chiu ◽  
Li-Chuan Weng ◽  
Hsin-Fu Liu ◽  
...  

Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections could improve clinical outcomes and reduce the use of antibiotics and treatment sessions. Advances in diagnostic technology contribute to the accurate detection of viruses. We performed a multiplex real-time polymerase chain reaction (PCR) to investigate the viral etiology in pediatric patients and compared the detection rates with those determined using traditional antigen tests and virus cultures. Fifteen respiratory viruses were included in our investigation: respiratory syncytial virus A/B (RSV), influenza virus A (FluA) and influenza virus B (FluB), human metapneumovirus (MPV), enterovirus (EV), human parainfluenza virus (PIV) types 1–4, human rhinovirus (RV), human coronavirus OC43, NL63, and 229E, human adenovirus (ADV), and human bocavirus (Boca). In total, 474 specimens were collected and tested. Respiratory viruses were detected more frequently by PCR (357, 75.3%) than they were by traditional tests (229, 49.3%). The leading pathogens were RSV (113, 23.8%), RV (72, 15.2%), PIV3 (53, 11.2%), FluA (51, 10.8%), and ADV (48, 10.1%). For children younger than 5 years, RSV and RV were most prevalent; for children older than 5 years, FluA and ADV were the most frequently detected. Of the specimens, 25.8% (92/357) were coinfected with two or more viruses. RV, Boca, PIV2, FluB, and PIV4 had higher rates of coinfection; MPV and PIV1 had the lowest rates of coinfection (9.1% and 5.3%). To conclude, the detection power of PCR was better than that of traditional antigen tests and virus cultures when considering the detection of respiratory viruses. RSV and RV were the leading viral pathogens identified in the respiratory specimens. One-quarter of the positive specimens were coinfected with two or more viruses. In the future, further application of PCR may contribute to the rapid and accurate diagnosis of respiratory viruses and could improve patient outcomes.


2020 ◽  
Vol 14 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Ronald Eccles

Introduction: The common cold syndrome of acute upper respiratory tract viral infection is the most common disease among mankind and is an extremely common illness in children. There is a great need for a safe and effective antiviral treatment with minimal side effects. The challenge in developing a treatment is the numerous and varied respiratory viruses that cause this common illness and the need for a treatment with good tolerability and safety. Explanation: All respiratory viruses must reach the cell surface by passing through respiratory fluid and mucus, and this common feature may allow for the development of antivirals that capture viruses during this transit. This article discusses how large polyanionic molecules such as iota-carrageenan may trap positively charged respiratory viruses. Iota-carrageenan is a large polysaccharide molecule which is neither absorbed from the respiratory tract nor metabolised. It, therefore, does not have any pharmacological properties. Iota-carrageenan nasal spray has been shown to reduce the titres of respiratory viruses and to reduce the severity of symptoms in placebo-controlled clinical trials, including children and adults. The results of four clinical trials are presented. Conclusion: Iota-carrageenan is a good candidate as a safe and effective non-specific antiviral treatment for common cold, and more research is justified on polyanionic molecules like carrageenans as antivirals.


Author(s):  
Dr Mark Harrison

15.1 Rhinovirus, 209 15.2 Influenza, 210 15.3 Parainfluenza, 211 15.4 Respiratory syncytial virus (RSV), 211 • There are more than 100 different serotypes of rhinovirus. • Rhinovirus is chiefly limited to upper respiratory tract infections and is the major cause of the common cold....


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