Patterns of antibody response during natural hRSV infection: insights for the development of new antibody-based therapies.

INTRODUCTION: The human respiratory syncytial virus (hRSV) is the main cause of acute lower respiratory tract infection in susceptible population worldwide, such as young children and the elderly. Although hRSV is a major public health burden, there are no licensed vaccines and the only available therapy is palivizumab. During life, reinfections with hRSV are common, suggesting that the virus can impair the development of an efficient host immune response. This feature has hindered the development of efficient therapies. AREAS COVERED: This article focuses on research about the natural development of antibodies in humans after the exposure to hRSV. The difficulties of developing anti-hRSV therapies based on monoclonal antibodies have been recently associated to the relationship between the disease outcome and the pattern of antibody response. EXPERT OPINION: Development of monoclonal antibodies is a potentially successful approach to prevent the population from suffering severe respiratory diseases caused by hRSV infection, for which there are no available vaccines. Although the use of palivizumab is safe, its effectiveness is controversial. Recent data have prompted research to develop therapies targeting alternative viral antigens, rather than focusing only on the F protein, as well as the development of antibodies with a cell-mediated function.

Facile and rapid detection of respiratory syncytial virus using metallic nanoparticles.

BACKGROUND: Respiratory syncytial virus (RSV) causes severe respiratory infection in infants, children and elderly. Currently, there is no effective vaccine or RSV specific drug for the treatment. However, an antiviral drug ribavirin and palivizumab is prescribed along with symptomatic treatment. RSV detection is important to ensure appropriate treatment of children. Most commonly used detection methods for RSV are DFA, ELISA and Real-time PCR which are expensive and time consuming. Newer approach of plasmonic detection techniques like localized surface plasmon resonance (LSPR) spectroscopy using metallic nanomaterials has gained interest recently. The LSPR spectroscopy is simple and easy than the current biophysical detection techniques like surface-enhanced Raman scattering (SERS) and mass-spectroscopy. RESULTS: In this study, we utilized LSPR shifting as an RSV detection method by using an anti-RSV polyclonal antibody conjugated to metallic nanoparticles (Cu, Ag and Au). Nanoparticles were synthesized using alginate as a reducing and stabilizing agent. RSV dose and time dependent LSPR shifting was measured for all three metallic nanoparticles (non-functionalized and functionalized). Specificity of the functionalized nanoparticles for RSV was evaluated in the presence Pseudomonas aeruginosa and adenovirus. We found that functionalized copper nanoparticles were efficient in RSV detection. Functionalized copper and silver nanoparticles were specific for RSV, when tested in the presence of adenovirus and P. aeruginosa, respectively. Limit of detection and limit of quantification values reveal that functionalized copper nanoparticles are superior in comparison with silver and gold nanoparticles. CONCLUSIONS: The study demonstrates successful application of LSPR for RSV detection, and it provides an easy and inexpensive alternative method for the potential development of LSPR-based detection devices.

Contribution of Fcγ receptors to human respiratory syncytial virus pathogenesis and the impairment of T-cell activation by dendritic cells.

Human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization related to respiratory disease. Infection with hRSV produces abundant infiltration of immune cells into the airways, which combined with an exacerbated pro-inflammatory immune response can lead to significant damage to the lungs. Human RSV re-infection is extremely frequent, suggesting that this virus may have evolved molecular mechanisms that interfere with host adaptive immunity. Infection with hRSV can be reduced by administering a humanized neutralizing antibody against the virus fusion protein in high-risk infants. Although neutralizing antibodies against hRSV effectively block the infection of airway epithelial cells, here we show that both, bone marrow-derived dendritic cells (DCs) and lung DCs undergo infection with IgG-coated virus (hRSV-IC), albeit abortive. Yet, this is enough to negatively modulate DC function. We observed that such a process is mediated by Fcγ receptors (FcγRs) expressed on the surface of DCs. Remarkably, we also observed that in the absence of hRSV-specific antibodies FcγRIII knockout mice displayed significantly less cellular infiltration in the lungs after hRSV infection, compared with wild-type mice, suggesting a potentially harmful, IgG-independent role for this receptor in hRSV disease. Our findings support the notion that FcγRs can contribute significantly to the modulation of DC function by hRSV and hRSV-IC. Further, we provide evidence for an involvement of FcγRIII in the development of hRSV pathogenesis.

Molecular characterization of respiratory syncytial viruses infecting children reported to have received palivizumab immunoprophylaxis.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ. OBJECTIVE: To detect PZ resistance conferring mutations in RSV strains from children who received PZ. STUDY DESIGN: Children aged ≤ 24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods. RESULTS: Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt. CONCLUSIONS: Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance.