Human respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection, such as bronchiolitis, bronchitis, or pneumonia, in both infants and the elderly. Despite the global burden of diseases attributable to RSV infection, no clinically approved vaccine is available, and a humanized monoclonal antibody for prophylaxis is not readily affordable in developing countries. There are several hurdles to the successful development of RSV vaccines: immune-vulnerable target populations such as premature infants, pregnant women, and immunocompromised people; safety concerns associated with vaccine-enhanced diseases; repeated infection; and waning memory. To develop successful strategies for the prevention of RSV infection, it is necessary to understand the protective and pathologic roles of host immune responses to RSV infection. In this review, we will summarize the positive and negative relationship between RSV infection and host immunity and discuss strategies for the development of the first successful RSV vaccine.
Humans ; Immunity ; Immunocompromised Host ; Respiratory Syncytial Virus Infections/immunology/*prevention & control ; *Respiratory Syncytial Virus Vaccines ; Respiratory Syncytial Viruses/*physiology

The respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and subfamily Pneumovirinae. The RSV can cause acute infections of the lower respiratory tract in infants. The F gene of the RSV is a conservative gene and varies only slightly in its expression. Few studies focusing on the variability of the F gene have been carried out. F protein (fusion glycoprotein) is a transmembrane glycoprotein that mediates fusion and penetration between the virus and host cells. Neutralizing antibody against the F protein can protect against infection by RSV subtypes A and B. Hence, F protein has become the main target for the development of a monoclonal antibody and vaccine against the RSV. An effective vaccine is not available, so a monoclonal antibody against F protein is now the most important method to reduce the morbidity and severity associated with RSV infection in high-risk children. However, a monoclonal antibody can lead to the production of drug-resistant strains of the RSV. This review focuses on genetic variation of the F gene of the RSV as well as progress in the development of a monoclonal antibody against F protein and a vaccine in the last decade.
Animals ; Antibodies, Monoclonal ; immunology ; Humans ; Respiratory Syncytial Virus Infections ; immunology ; prevention & control ; virology ; Respiratory Syncytial Viruses ; genetics ; immunology ; Viral Fusion Proteins ; genetics ; immunology ; Viral Vaccines ; genetics ; immunology

OBJECTIVETo probe the epidemiological trend of respiratory syncytial virus (RSV) and cellular immunological change of RSV bronchopneumonia among children in Suzhou in the past five years.

METHODS10,205 children with acute respiratory tract infection from January 2001 to December 2005 were enrolled into the study. Nasopharyngeal aspirates were obtained from the respiratory tract by aseptic vacuum aspiration. Direct immuno-fluorescence assay was employed to detect seven kinds of virus antigens including RSV antigen. CD3, CD4, CD8, CD19, CD16 and CD56 in peripheral blood mononuclear cells of 30 patients with RSV bronchopneumonia (1.5-24.0 months old group) were analyzed by flow cytometry analysis, and 15 normal infants (1.5-24.0 months old group) were enrolled as control group.

RESULTSThe annual positive rate of RSV was 24.94%, 25.83%, 24.05%, 25.39% and 27.30% respectively from 2001 to 2005. It also found that the peak season for RSV infection was spring or winter (January to March or November to December). The positive rate of RSV was significantly higher in 1-12 months old group than that in > 12 months old group (chi2 = 97.320, P < 0.01), as well as the groups between 1-12 months old (chi2 = 7.804, P < 0.05, the highest positive rate was occurred at 3-6 months old group). The positive rate of RSV was significantly higher in boys than that in girls (chi2 = 9.693, P < 0.01). The percentages of CD3+, CD4+, CD8+ and NK (CD16 + 56)+ cells were significantly lower in RSV bronchopneumonia than those in control group (t = 3.199, P < 0.01; t = 2.215, P < 0.05; t = 2.619, P < 0.05 and t = 5.240, P < 0.01, respectively). While the percentage of CD19+ cells was significantly elevated in RSV bronchopneumonia than that in control group (t = 2.875, P < 0.01).

CONCLUSIONRSV infection is of obvious seasonal changes. The younger the patient, the higher positive rates of RSV infection is, while and the cellular immunity function is lower. The effective measures for preventing RSV infection are important, especially for the infants. Further investigation is necessary to understand the causes of the variations for RSV infections between boys and girls.

Adolescent ; Bronchopneumonia ; epidemiology ; immunology ; virology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Respiratory Syncytial Virus Infections ; epidemiology ; immunology ; Respiratory Syncytial Viruses

Adenoviridae ; immunology ; Antigens, Viral ; analysis ; Child ; Fluorescent Antibody Technique ; Humans ; Respiratory Syncytial Viruses ; immunology ; Respiratory Tract Infections ; immunology ; Respirovirus ; immunology ; Virus Diseases ; immunology

This investigation enrolled 570 healthy young males gathered from all over the country for military service at the Republic of Korea Air Force boot camp. It confirmed RSV IgG seroprevalence by utilizing the enzyme immunoassay method just prior to undergoing basic training. The mean age of this study was 20.25+/-1.34 yr old. The results of their immunoassay seroprofiles showed that 561 men (98.4%) were positive, 2 (0.4%) were negative and 7 (1.2%) were equivocal belonging to the grey zone. It was confirmed that RSV is a common respiratory virus and RSV infection was encountered by almost all people before reaching adulthood in Korea. Nine basic trainees belonging to the RSV IgG negative and equivocal grey zone categories were prospectively observed for any particular vulnerability to respiratory infection during the training period of two months. However, these nine men completed their basic training without developing any specific respiratory illness.
Adult ; Antibodies, Viral/*blood ; Humans ; Immunoenzyme Techniques ; Immunoglobulin G/*blood ; Male ; Military Personnel ; Respiratory Syncytial Virus Infections/*epidemiology ; Respiratory Syncytial Viruses/*immunology ; Seroepidemiologic Studies ; Young Adult

AIMTo study the relation between Respiratory Syncytial Virus infection and asthma development by measuring airway responsiveness (AR) and M2R function.

METHODSGuinea pigs (n = 34) were randomly divided into 4 groups: Hep-2/NS group (group A, n = 9), RSV/NS group (group B, n =9), Hep-2/OVA group (group C, n = 8) and RSV/OVA group(group D, n = 8). On day 21 after infection we tested AR and M2R. Then counted eosinophils in BALF and observed pathological change.

RESULTSIntraairway pressure(IP mmH20) of group B had no significant difference with group A(P > 0.01), and the extent of IP decrease also had no difference between groups A and B (P > 0. 05), but IP of C group were much higher than group A (P<0.05), with extent of IP decrease lower than group A (P < 0.05). And IP of group D were higher than group C (P < 0.01), with the extent of IP decrease much lower than group C (P < 0.05).

CONCLUSIONRSV infection could enhance OVA-induced M2R dysfunction, then develop AHR.

Animals ; Asthma ; immunology ; physiopathology ; virology ; Bronchial Hyperreactivity ; immunology ; physiopathology ; virology ; Female ; Guinea Pigs ; Male ; Ovalbumin ; immunology ; Random Allocation ; Receptor, Muscarinic M2 ; physiology ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; immunology

OBJECTIVE: To explore the mechanisms for an increase in susceptibility of asthma induced by respiratory syncytial virus (RSV), to observe the expression of interleukin-8 (IL-8) in human bronchial epithelial cells (HBECs) after RSV infection and to invesigate the regulatory effect of IL-8 on Th17/Treg differentiation.
 METHODS: HBECs were divided into a control group and a RSV infected group. The RSVE-infected model of HBECs was established and examined. The expression of IL-8 mRNA was detected by real-time PCR, and the levels of IL-8 were measured by ELISA. Peripheral blood lymphocytes in healthy people were extracted and divided into a control group and an IL-8 treatment group. Based on concentration of IL-8 in RSV-infected HBECs, lymphocytes were treated by a matched concentration of human recombinant IL-8 for 24 h. The distribution of Th17 and Treg subsets in lymphocytes were examined by flow cytometry.
 RESULTS: The RSV-infected HBECs model was successfully established. The infected HBECs were still able to split and passage. The RSV could be detected in every passage in the infected cells. Virus particles indicated by bright yellow green fluorescence were seen under fluorescence microscope. Edema of mitochondrias, expansion of endoplasmic reticulum, fissure around nucleus and intracellular virus particles were all observed under electron microscope. The expression IL-8 mRNA were significantly enhanced in the RSV-infected group, and the level of IL-8 in the RSV-infected group was higher than that in the control group (P<0.05). After IL-8 treatment for 24 h, the ratio of Th17 subsets in lymphocytes were dramatically increased compared to the control group (P<0.05), but there was no difference in the ratio of Treg subsets between the 2 groups (P>0.05).
 CONCLUSION Over-secretion of IL-8 by the RSV-infected HBECs may promote the differentiation of Th17 subsets and maintain the Th17/Tred imbalance.
Cell Differentiation ; Cells, Cultured ; Epithelial Cells ; drug effects ; virology ; Flow Cytometry ; Humans ; Interleukin-8 ; immunology ; pharmacology ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins ; pharmacology ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology

OBJECTIVETo construct a human phage display antibody library, which will help to develop new drugs and vaccines against respiratory syncytial virus (RSV) and solve many of the issues that have limited the progression and application of murine monoclonal antibodies (McAbs) in the clinic. This can provide a platform for human antibody preparation and diagnosis, prophylaxis and therapy of RSV infection in children.

METHODSPeripheral blood lymphocytes were isolated from 52 children with RSV infection. cDNA was synthesized from the total RNA of lymphocytes. The light and heavy chain Fd (VH-CH1) fragments of immunoglobulin gene were amplified by RT-PCR. The amplified products were cloned into phagemid vector pComb3x and the clone samples were electrotransformed into competent E.coli XL1-Blue. The transformed cells were then infected with M13K07 helper phage to yield recombinant phage antibody of Fabs. The plasmids extracted from amplified E.coli were digested with restriction endonucleases Sac I, Xba I, Spe I and Xho I to monitor the insertion of the light or heavy chain Fd genes. RSV virions were utilized as antigens to screen Fab antibodies.

RESULTSBy recombination of light and heavy chain genes, an immune Fab phage display antibody library against RSV containing 2.08x10(7) different clones was constructed, in which 70% clones had light chains and heavy chain Fd genes. The capacity of Fab phage antibody gene library was 1.46x10(7) and the titre of the original Fab antibody library was about 1.06x10(12) pfu/mL. The antibody library gained an enrichment in different degrees after the preliminary panning.

CONCLUSIONSUtilizing the technology of phage display, an immune Fab phage display antibody library against RSV was successfully constructed in this study, which laid a valuable experimental foundation for further study and created favorable conditions for preparing human McAbs. This may also contribute to the improvement in the diagnosis, therapy and prophylaxis of RSV infection in children.

Antibodies, Viral ; genetics ; Bacteriophages ; genetics ; Child ; Humans ; Immunoglobulin Fab Fragments ; genetics ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin Light Chains ; genetics ; Peptide Library ; Respiratory Syncytial Viruses ; immunology

Acute Disease ; Adolescent ; Asthma ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; RNA, Viral ; genetics ; Respiratory Syncytial Viruses ; genetics ; Respiratory Tract Infections ; immunology ; virology ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effects of leukotriene receptor antagonist on the levels of Th1 and Th2 cytokines and the serum cysteinyl leukotrenes (CysLTs) in infants and young children with respiratory syncytial virus (RSV) pneumonia.

METHODSThirty-seven infants and young children with RSV pneumonia were divided into two groups after discharge. The cases in group 1 (n=24) were treated with a leukotriene receptor antagonist, Singulair 4 mg once daily for 12 weeks; the cases in group 2 (n=13) were treated with budesonide aerosol 200 ug once or twice daily for 12 weeks. The serum CysLTs, IFN-gamma and IL-4 were detected with enzyme_linked immunosorbent assays (ELISA) for all the 37 cases, and 10 healthy infants of the same age served as controls.

RESULTSThe serum CysLTs level in the cases with RSV pneumonia was significantly higher than that in controls (P<0.05). There was an imbalance in expression of Th1 and Th2 cytokines (IFN-gamma and IL-4 ) in these cases. Both Singulair and budesonide aerosol could correct the imbalance of Th1 and Th2 cytokines. The serum CysLTs level declined after treatment with Singulair in 24 cases, but no significant change occurred after treatment with budesonide aerosol in the remaining 13 cases.

CONCLUSIONSThe serum CysLTs level in children with RSV pneumonia was higher than that in healthy children, and there was an imbalance of Th1 and Th2 cytokines in these infants, which was similar to those with asthma. Leukotriene receptor antagonist may be effective in preventing children with RSV pneumonia from evolving into asthma.

Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Infant ; Leukotriene Antagonists ; administration & dosage ; pharmacology ; Male ; Pneumonia, Viral ; drug therapy ; immunology ; virology ; Respiratory Syncytial Virus Infections ; drug therapy ; immunology ; virology ; Respiratory Syncytial Viruses ; drug effects ; immunology ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology