scholarly journals Induction of Trained Immunity by Recombinant Vaccines

2021 ◽  
Vol 11 ◽  
Author(s):  
Camila Covián ◽  
Mariana Ríos ◽  
Roslye V. Berríos-Rojas ◽  
Susan M. Bueno ◽  
Alexis M. Kalergis
Keyword(s):  
Adaptive Immunity ◽  
Public Health Problem ◽  
The Elderly ◽  
Recombinant Vaccines ◽  
Respiratory Pathogens ◽  
Trained Immunity ◽  
Specific Memory ◽  
Pathogenic Viruses ◽  
Syncytial Virus ◽  
Recombinant Bcg

Vaccines represent an important strategy to protect humans against a wide variety of pathogens and have even led to eradicating some diseases. Although every vaccine is developed to induce specific protection for a particular pathogen, some vaccine formulations can also promote trained immunity, which is a non-specific memory-like feature developed by the innate immune system. It is thought that trained immunity can protect against a wide variety of pathogens other than those contained in the vaccine formulation. The non-specific memory of the trained immunity-based vaccines (TIbV) seems beneficial for the immunized individual, as it may represent a powerful strategy that contributes to the control of pathogen outbreaks, reducing morbidity and mortality. A wide variety of respiratory viruses, including respiratory syncytial virus (hRSV) and metapneumovirus (hMPV), cause serious illness in children under 5 years old and the elderly. To address this public health problem, we have developed recombinant BCG vaccines that have shown to be safe and immunogenic against hRSV or hMPV. Besides the induction of specific adaptive immunity against the viral antigens, these vaccines could generate trained immunity against other respiratory pathogens. Here, we discuss some of the features of trained immunity induced by BCG and put forward the notion that recombinant BCGs expressing hRSV or hMPV antigens have the capacity to simultaneously induce specific adaptive immunity and non-specific trained immunity. These recombinant BCG vaccines could be considered as TIbV capable of inducing simultaneously the development of specific protection against hRSV or hMPV, as well as non-specific trained-immunity-based protection against other pathogenic viruses.

scholarly journals Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 624
Author(s):  
Laura M. Stephens ◽  
Steven M. Varga
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Burden ◽  
Elderly Population ◽  
Vaccine Development ◽  
The Elderly ◽  
The United States ◽  
Susceptible Population ◽  
Age Related ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is most commonly associated with acute lower respiratory tract infections in infants and children. However, RSV also causes a high disease burden in the elderly that is often under recognized. Adults >65 years of age account for an estimated 80,000 RSV-associated hospitalizations and 14,000 deaths in the United States annually. RSV infection in aged individuals can result in more severe disease symptoms including pneumonia and bronchiolitis. Given the large disease burden caused by RSV in the aged, this population remains an important target for vaccine development. Aging results in lowered immune responsiveness characterized by impairments in both innate and adaptive immunity. This immune senescence poses a challenge when developing a vaccine targeting elderly individuals. An RSV vaccine tailored towards an elderly population will need to maximize the immune response elicited in order to overcome age-related defects in the immune system. In this article, we review the hurdles that must be overcome to successfully develop an RSV vaccine for use in the elderly, and discuss the vaccine candidates currently being tested in this highly susceptible population.

scholarly journals Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus

2021 ◽  
Vol 9 (6) ◽  
pp. 1293
Author(s):  
Gaspar A. Pacheco ◽  
Nicolás M. S. Gálvez ◽  
Jorge A. Soto ◽  
Catalina A. Andrade ◽  
Alexis M. Kalergis
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Human Respiratory Syncytial Virus ◽  
Respiratory Pathogens ◽  
Parainfluenza Viruses ◽  
Starting Point ◽  
The Social ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Polymicrobial Infections

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

Identification of determinants of healthy ageing in Italy: results from the national survey IDAGIT

2020 ◽  
pp. 1-21
Author(s):  
Erika Guastafierro ◽  
Ilaria Rocco ◽  
Rui Quintas ◽  
Barbara Corso ◽  
Nadia Minicuci ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Public Health Problem ◽  
The Elderly ◽  
Factor Loading ◽  
Healthy Ageing ◽  
World Health ◽  
Italian Population ◽  
Social Environments ◽  
Ageing Model ◽  
Health Organization

Abstract Healthy ageing is a public health problem globally. In Europe, the dependency ratio of the elderly is expected to increase by 21.6 per cent to 51.2 per cent in 2070. The World Health Organization (WHO) study on healthy ageing started in 2002 as a concept whereby all people of all ages should be able to live in a healthy, safe and socially inclusive way. The aim of this study is to present preliminary results of the project Identification of Determinants of Healthy Ageing in Italy (IDAGIT) that aimed to collect data on the active and healthy ageing of the Italian population aged over 18 using the conceptual framework of the WHO's ageing model. To link the determinants of the IDAGIT studies to those of the WHO model, we performed a confirmatory factor analysis which reported these variables as significant (in order of factor loading): smoking, cognition score, comorbidity, outdoor built environment, participation, working expertise and income. Considering comorbidity, 83.8 per cent of the sample declared not having any chronic diseases or to have only one, and regarding neurological diseases, only nine people had received a diagnosis of stroke. Regarding gender, the personal determinants and physical and social environments did not result in statistically significant differences, whereas we found statistical differences between the aged groups in all variables analysed. These results provide a first bio-psycho-social perspective on ageing in the Italian population.

scholarly journals Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2607
Author(s):  
Yuzhen Gao ◽  
Jingjing Cao ◽  
Pan Xing ◽  
Ralf Altmeyer ◽  
Youming Zhang
Keyword(s):  
Respiratory Syncytial Virus ◽  
Confidence Interval ◽  
The Elderly ◽  
Term Treatment ◽  
Fusion Inhibitors ◽  
Long Term Treatment ◽  
Statistical Program ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a major pathogen that causes severe lower respiratory tract infection in infants, the elderly and the immunocompromised worldwide. At present no approved specific drugs or vaccines are available to treat this pathogen. Recently, several promising candidates targeting RSV entry and multiplication steps are under investigation. However, it is possible to lead to drug resistance under the long-term treatment. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we tested in vitro two-drug combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine). The statistical program MacSynergy II was employed to determine synergism, additivity or antagonism between drugs. From the result, we found that combinations of ALS8176 and Ziresovir or GS5806 exhibit additive effects against RSV in vitro, with interaction volume of 50 µM2% and 31 µM2% at 95% confidence interval, respectively. On the other hand, all combinations between fusion inhibitors showed antagonistic effects against RSV in vitro, with volume of antagonism ranging from −50 µM2 % to −176 µM2 % at 95% confidence interval. Over all, our results suggest the potentially therapeutic combinations in combating RSV in vitro could be considered for further animal and clinical evaluations.

scholarly journals Trends, Coverage and Influencing Determinants of Influenza Vaccination in the Elderly: A Population-Based National Survey in Spain (2006–2017)

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 327
Author(s):  
Silvia Portero de la Cruz ◽  
Jesús Cebrino
Keyword(s):  
Influenza Vaccination ◽  
Chronic Diseases ◽  
Vaccination Coverage ◽  
Public Health Problem ◽  
Risk Groups ◽  
The Elderly ◽  
Population Based ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Significant Public Health

Influenza is a significant public health problem and the elderly are at a greater risk of contracting the disease. The vaccination coverage of the elderly is below the Spanish target of 65% for each influenza season. The aims of this study were to report the coverage of influenza vaccination in Spain among the population aged ≥65 years and high-risk groups for suffering chronic diseases, to analyze the time trends from 2006 to 2017 and to identify the factors which affect vaccination coverage. A nationwide cross-sectional study was conducted including 20,753 non-institutionalized individuals aged ≥65 years who had participated in the Spanish National Health Surveys in 2006, 2011/2012, and 2017. Sociodemographic, health-related variables, and influenza vaccination data were used. A logistic regression analysis was performed to determine the variables associated with influenza vaccination. Influenza vaccination coverage was 60%. By chronic condition, older people with high cholesterol levels and cancer had the lowest vaccination coverage (62.41% and 60.73%, respectively). This coverage declined from 2006 to 2017 in both groups. Higher influenza vaccination was associated with males, Spanish nationality, normal social support perceived, polypharmacy, worse perceived health, participation in other preventive measures, and increasing age and the number of chronic diseases.

scholarly journals Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 47
Author(s):  
Catalina A. Andrade ◽  
Alexis M. Kalergis ◽  
Karen Bohmwald
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Respiratory Infections ◽  
The Elderly ◽  
Cell Types ◽  
Potential Effect ◽  
Viral Agent ◽  
Pulmonary Manifestations ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

scholarly journals Chemokine regulation of inflammation during respiratory syncytial virus infection

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1837 ◽  
Author(s):  
Rinat Nuriev ◽  
Cecilia Johansson
Keyword(s):  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
Infection Process ◽  
Viral Control ◽  
Small Proteins ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Developed World ◽  
Immune Detection

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections especially in infants, immunocompromised individuals and the elderly and is the most common cause of infant hospitalisation in the developed world. The immune responses against RSV are crucial for viral control and clearance but, if dysregulated, can also result in immunopathology and impaired gas exchange. Lung immunity to RSV and other respiratory viruses begins with the recruitment of immune cells from the bloodstream into the lungs. This inflammatory process is controlled largely by chemokines, which are small proteins that are produced in response to innate immune detection of the virus or the infection process. These chemokines serve as chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes. In this review, we highlight recent advances in the field of RSV infection and disease, focusing on how chemokines regulate virus-induced inflammation.

scholarly journals Lentiviral and AAV-mediated Expression of Palivizumab Offer protection against Respiratory Syncytial Virus infection

2021 ◽  
Author(s):  
Agata Antepowicz ◽  
Omar Habib ◽  
Freja Kirsebom ◽  
Cecilia Johansson ◽  
Deborah R. Gill ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vulnerable Populations ◽  
The Elderly ◽  
Complete Protection ◽  
Adeno Associated Virus ◽  
Common Cause ◽  
Immunodeficiency Virus ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) infection is a common cause of hospitalisation in infants and the elderly. Palivizumab prophylaxis is the only approved treatment modality but is costly and only offered to select vulnerable populations. Here, we investigated gene delivery approaches via recombinant adeno-associated virus (rAAV2/8) and simian immunodeficiency virus (rSIV.F/HN) vectors to achieve sustained in vivo production of palivizumab in a murine model. Delivery of palivizumab-expressing vectors 28 days prior to RSV challenge resulted in complete protection from RSV-induced weight loss. This approach offers prophylaxis against RSV infection, allowing for wider use and reduction in treatment costs in vulnerable populations.

scholarly journals Circulation of Respiratory Viruses in Hospitalized Adults before and during the COVID-19 Pandemic in Brescia, Italy: A Retrospective Study

2021 ◽  
Vol 18 (18) ◽  
pp. 9525
Author(s):  
Maria Antonia De Francesco ◽  
Caterina Pollara ◽  
Franco Gargiulo ◽  
Mauro Giacomelli ◽  
Arnaldo Caruso
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Statistical Significance ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Contact Tracing ◽  
Nucleic Acid Detection ◽  
Respiratory Pathogens ◽  
Syncytial Virus ◽  
Human Coronaviruses

Different preventive public health measures were adopted globally to limit the spread of SARS-CoV-2, such as hand hygiene and the use of masks, travel restrictions, social distance actions such as the closure of schools and workplaces, case and contact tracing, quarantine and lockdown. These measures, in particular physical distancing and the use of masks, might have contributed to containing the spread of other respiratory viruses that occurs principally by contact and droplet routes. The aim of this study was to evaluate the prevalence of different respiratory viruses (influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, 3 and 4, rhinovirus, adenovirus, metapneumovirus and human coronaviruses) after one year of the pandemic. Furthermore, another aim was to evaluate the possible impact of these non-pharmaceutical measures on the circulation of seasonal respiratory viruses. This single center study was conducted between January 2017–February 2020 (pre-pandemic period) and March 2020–May 2021 (pandemic period). All adults >18 years with respiratory symptoms and tested for respiratory pathogens were included in the study. Nucleic acid detection of all respiratory viruses was performed by multiplex real time PCR. Our results show that the test positivity for influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus and human coronaviruses decreased with statistical significance during the pandemic. Contrary to this, for adenovirus the decrease was not statistically significant. Conversely, a statistically significant increase was detected for rhinovirus. Coinfections between different respiratory viruses were observed during the pre-pandemic period, while the only coinfection detected during pandemic was between SARS-CoV-2 and rhinovirus. To understand how the preventive strategies against SARS-CoV-2 might alter the transmission dynamics and epidemic patterns of respiratory viruses is fundamental to guide future preventive recommendations.

scholarly journals Community factors associated with local epidemic timing of respiratory syncytial virus: A spatiotemporal modeling study

2021 ◽  
Vol 7 (26) ◽  
pp. eabd6421
Author(s):  
Zhe Zheng ◽  
Virginia E. Pitzer ◽  
Joshua L. Warren ◽  
Daniel M. Weinberger
Keyword(s):  
New York ◽  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
Spatiotemporal Modeling ◽  
Geographic Proximity ◽  
Community Factors ◽  
Harmonic Regression ◽  
Syncytial Virus ◽  
Zip Code ◽  
Epidemic Timing

Respiratory syncytial virus (RSV) causes a large burden of morbidity in young children and the elderly. Spatial variability in the timing of RSV epidemics provides an opportunity to probe the factors driving its transmission, including factors that influence epidemic seeding and growth rates. Using hospitalization data from Connecticut, New Jersey, and New York, we estimated epidemic timing at the ZIP code level using harmonic regression and then used a Bayesian meta-regression model to evaluate correlates of epidemic timing. Earlier epidemics were associated with larger household size and greater population density. Nearby localities had similar epidemic timing. Our results suggest that RSV epidemics grow faster in areas with more local contact opportunities, and that epidemic spread follows a spatial diffusion process based on geographic proximity. Our findings can inform the timing of delivery of RSV extended half-life prophylaxis and maternal vaccines and guide future studies on the transmission dynamics of RSV.

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