Advances in and the potential of vaccines for respiratory syncytial virus

Jorquera, Patricia A.; Oakley, Katie; Tripp, Ralph A.

doi:10.1586/17476348.2013.814409

Cited by 13 publications

(9 citation statements)

References 158 publications

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“…The original formalin-inactivated vaccine developed in the 1960s lead to enhanced inflammatory disease and death of infants [ 11 , 12 ] and despite the decades of study since there is still no FDA approved vaccine for RSV [ 13 , 14 ]. A better understanding of the mechanisms of RSV immune evasion may facilitate the development of a safe and effective vaccine.…”

Section: Introductionmentioning

confidence: 99%

Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase

et al. 2016

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Respiratory syncytial virus (RSV) has been reported to infect human mesenchymal stem cells (MSCs) but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts. RSV-infected MSCs showed differentially altered expression of cytokines and chemokines such as IL-1β, IL6, IL-8 and SDF-1 compared to epithelial cells. Notably, RSV-infected MSCs exhibited significantly increased expression of IFN-β (~100-fold) and indoleamine-2,3-dioxygenase (IDO) (~70-fold) than in mock-infected MSCs. IDO was identified in cytosolic protein of infected cells by Western blots and enzymatic activity was detected by tryptophan catabolism assay. Treatment of PBMCs with culture supernatants from RSV-infected MSCs reduced their proliferation in a dose dependent manner. This effect on PBMC activation was reversed by treatment of MSCs with the IDO inhibitors 1-methyltryptophan and vitamin K3 during RSV infection, a result we confirmed by CRISPR/Cas9-mediated knockout of IDO in MSCs. Neutralizing IFN-β prevented IDO expression and activity. Treatment of MSCs with an endosomal TLR inhibitor, as well as a specific inhibitor of the TLR3/dsRNA complex, prevented IFN-β and IDO expression. Together, these results suggest that RSV infection of MSCs alters their immune regulatory function by upregulating IFN-β and IDO, affecting immune cell proliferation, which may account for the lack of protective RSV immunity and for chronicity of RSV-associated lung diseases such as asthma and COPD.

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Section: Introductionmentioning

confidence: 99%

Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase

et al. 2016

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“…The World Health Organization has estimated that the annual global disease burden is more than 64 million HRSV infections and 160,000 deaths related to HRSV infection (World Health Organization (WHO), 2009). HRSV infection is a major concern in developed and developing countries, but no effective vaccine is available and immunoprophylaxis is the only treatment for preventing HRSV infection, although access is limited (Chang, 2011;Rudraraju et al, 2013;Graham, 2011;Jorquera et al, 2013;Shaw et al, 2013;Wang et al, 2011a;Zeitlin et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Rapid replacement of human respiratory syncytial virus A with the ON1 genotype having 72 nucleotide duplication in G gene

Kim

Lee

et al. 2014

Infection, Genetics and Evolution

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Human respiratory syncytial virus (HRSV) is the main cause of severe respiratory illness in young children and elderly people. We investigated the genetic characteristics of the circulating HRSV subgroup A (HRSV-A) to determine the distribution of genotype ON1, which has a 72-nucleotide duplication in attachment G gene. We obtained 456 HRSV-A positive samples between October 2008 and February 2013, which were subjected to sequence analysis. The first ON1 genotype was discovered in August 2011 and 273 samples were identified as ON1 up to February 2013. The prevalence of the ON1 genotype increased rapidly from 17.4% in 2011-2012 to 94.6% in 2012-2013. The mean evolutionary rate of G protein was calculated as 3.275 × 10(-3) nucleotide substitution/site/year and several positively selected sites for amino acid substitutions were located in the predicted epitope region. This basic and important information may facilitate a better understanding of HRSV epidemiology and evolution.

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“…No effective vaccine against RSV is currently available, and the burden of disease urges us to move towards new and creative interventions without the risk taken in previous strategies . In order to promote the development of RSV vaccines, several major challenges must be overcome.…”

Section: Discussionmentioning

confidence: 99%

Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants

Souza

Freitas

Fernandes

et al. 2015

Clinical and Experimental Immunology

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Summary Respiratory syncytial virus (RSV)-specific CD81 T cell responses do not protect against reinfection. Activation of mammalian target of rapamycin (mTOR) impairs memory CD8 1 T cell differentiation. Our hypothesis was that RSV inhibits the formation of CD8 1 T cells memory responses through mTOR activation. To explore this, human and mouse T cells were used. RSV induced mTOR phosphorylation at Ser2448 in CD8 T cells. mTOR activation by RSV was completely inhibited using rapamycin. RSV-infected children presented higher mTOR gene expression on nasal washes comparing to children infected with metapneumovirus and rhinovirus. In addition, RSV-infected infants presented a higher frequency of CD8 1 pmTORser2448 1 T cells in nasal washes compared to RSV-negative infants.Rapamycin treatment increased the frequency of mouse CD8 RSV-M 282-90 pentamer-positive T cells and the frequency of RSV-specific memory T cells precursors. These data demonstrate that RSV is activating mTOR directly in CD8 T cells, indicating a role for mTOR during the course of RSV infection.

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Advances in and the potential of vaccines for respiratory syncytial virus

Cited by 13 publications

References 158 publications

Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase

Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase

Rapid replacement of human respiratory syncytial virus A with the ON1 genotype having 72 nucleotide duplication in G gene

Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants

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