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

To construct plasmid of recombinant protein candidate vaccine of respiratory syncytial virus, express it in E. coli, and to investigate its immunogenicity and protective efficacy. A CD8+ T cell epitope from respiratory syncytial virus (RSV) M2 protein F/M2:81 - 95 and the G:125-225 (G1) gene fragments from RSV-G protein containing B cell epitopes were amplified by PCR method and then inserted into the prokaryotic expression vector pET-DsbA after bonding to a linker. The fusion protein DsbA-G1-Linker-F/M2:81-95 (D-G1LF/M2) was expressed successfully in E. coli BL21 (DE3). The product was proved to be RSV-specific by Western-blot. After purified by affinity chromatography on Ni+ Sepharose and renatured by gradient dialysis. D-G1LF/M2 was used to immune BALB/c mice. D-G1LF/M2 induced high anti-D-G1LF/M2 IgG, anti-RSV IgG and neutralizing antibody titers in serum and lung of BALB/c mice, and elicied RSV-specific CTL responses. The IgG subclass distribution revealed that IgG1/IgG2a ratio was 2.66. Viral titration indicated that D-G1LF/M2 could protect BALB/c mice against RSV challenge in lung.
Animals ; Antibodies, Viral ; blood ; immunology ; Escherichia coli ; genetics ; metabolism ; Humans ; Immunoglobulin G ; blood ; immunology ; Mice ; Mice, Inbred BALB C ; Plasmids ; genetics ; immunology ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; Respiratory Syncytial Virus Infections ; prevention & control ; Respiratory Syncytial Virus Vaccines ; biosynthesis ; genetics ; immunology ; Respiratory Syncytial Virus, Human ; genetics ; immunology ; Viral Envelope Proteins ; genetics ; Viral Fusion Proteins ; genetics ; Viral Proteins ; genetics

OBJECTIVENeonatal Bacillus Calmette-Guerin (BCG) vaccination could decrease asthma prevalence in human according to "hygiene hypothesis". The authors proposed a hypothesis that effect of BCG vaccination on inhibiting asthma in human might be reversed by respiratory virus infection. The objective of this study was to observe combined effects of neonatal BCG vaccination and respiratory syncytial virus (RSV) infection on experimental asthma in mice.

METHODSNeonatal BALB/c mice were divided into five groups. Control and ovalbumin (OVA) groups were mock-vaccinated at birth and mock-infected at 3 weeks of age. BCG + OVA group was BCG-vaccinated and mock-infected. RSV + OVA group was mock-vaccinated and RSV-infected. BCG + RSV + OVA group was BCG-vaccinated and RSV-infected. Except for control group, all the other groups underwent ovalbumin (OVA) sensitization and challenge. Airway responsiveness to inhaled methacholine was measured and bronchoalveolar lavage (BAL) was performed after the last challege. Cells in BAL fluid (BALF) were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lungs was scored by staining with hematoxylin and eosin.

RESULTS(1) The numbers of total white cells, lymphocytes, monocytes, neutrophils, and eosinophils in the BALF from all OVA-sensitized/challenged groups were significantly greater than those in control (P < 0.01), and BCG + OVA group had significantly lower total white cells, lymphocytes and eosinophils as compared with other OVA-sensitized/challenged groups (P < 0.05 or 0.01). (2) All OVA-sensitized/challenged groups had significantly lower IFNgamma (P < 0.05) and higher IL-4 (P < 0.05) level in BALF as compared with control, but there was no significant difference among all OVA sensitized/challenged groups. There was no significant difference in IL-10 level between all experimental groups. (3) All OVA-sensitized/challenged groups showed significantly higher serum OVA-specific IgE titers than control (P < 0.05 or 0.01), but no significant difference was found among all OVA sensitized/challenged groups. (4) RSV + OVA and BCG + RSV + OVA groups displayed the highest airway resistance and subsequently in order as follows: OVA group, BCG + OVA group and control group in severity of airway hyperreactivity (AHR), but no significant difference was found between RSV + OVA and BCG + RSV + OVA groups. (5) Histological score of peribronchiolitis, perivasculitis, alveolitis, and peribronchial eosinophilia in all OVA-sensitized/challenged groups was significantly higher than that in control. BCG + OVA group had significantly milder peribronchiolitis and peribronchial eosinophilia than the other OVA-sensitized/challenged groups (P < 0.05) and significantly milder alveolitis than OVA and BCG + RSV + OVA groups (P < 0.05).

CONCLUSIONNeonatal BCG vaccination decreased asthmatic inflammation and AHR and RSV infection could reverse anti-asthma effect of neonatal BCG vaccination in OVA-sensitized/challenged mouse model.

Animals ; Animals, Newborn ; Asthma ; immunology ; prevention & control ; BCG Vaccine ; administration & dosage ; immunology ; pharmacology ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; drug effects ; immunology ; secretion ; Immunoglobulin E ; analysis ; immunology ; Interferon-gamma ; analysis ; immunology ; Interleukin-10 ; analysis ; immunology ; Interleukin-4 ; analysis ; immunology ; Leukocytes ; drug effects ; immunology ; secretion ; Lung ; drug effects ; immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; administration & dosage ; immunology ; toxicity ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; immunology ; pathogenicity ; Treatment Outcome