Respiratory Syncytial Virus Infections in Infants: Detel1ninants of Clinical Severity

In 1955 a virus was isolated by Morris et al. from a chimpanzee with an upper respiratory tract infection. This apparently new virus was originally called chimpanzee coryza agent. Soon aftclwards, when it was isolated from children with respiratory disease, it became clear that this virus was a major human pathogen. The virus was from then onward called respiratory syncytial virus (RSV) because of its ability to caLise respiratory disease and to induce large syncytia in cell culture. RSV is now known as the single most common cause of severe respiratory tract infection in childhood. In fact up to 70% of hospital admissions of infants for respiratory infections during the winter season may be caused by RSV alone. Soon after RSV was found to be a significant cause of morbidity and 1ll00iaiity in childhood the search for a vaccine began. During the sixties a formalin inactivated RSV (FI-RSV) candidate vaccine, known as "lot 100", was developed and administered to children of two to seven years old. This vaccine, in stead of protecting vaccinees against RSV infection, predisposed for more severe disease upon natural infection in the following RSV season. Hospitalization rates were as high as 80% and two of the vaccinces died. At this moment, despite considerable research efforts, no licensed vaccine is available against this important pathogen. Development ofa vaccine against RSV is one of the priorities of the Global Program for Vaccines of the World Health Organization

G protein variation in respiratory syncytial virus group A does not correlate with clinical severity

Respiratory syncytial virus group A strain variations of 28 isolates from The Netherlands collected during three consecutive seasons were studied by ana

Patient-to-patient spread of a single strain of Corynebacterium striatum causing infections in a surgical intensive care unit

Over a 12-month period, Corynebacterium striatum strains were isolated from clinical specimens from 14 patients admitted to a surgical intensive care unit. These isolates were identical by morphology and biotype and displayed the same antibiogram. Ten isolates were found to be the sole possible pathogen. These 10 isolates were from six patients, three of whom had signs of infection at the time of positive culture. Further typing was performed by random amplification of polymorphic DNA analysis, by which all strains were identical and were found to differ to various degrees from reference strains and from isolates found in clinical samples from other wards. In a case-control study the only independent risk factor for acquiring the strain was intubation for longer than 24 h (odds ratio, 20.09; 95

Identification of a common HLA-DP4-restricted T-cell epitope in the conserved region of the respiratory syncytial virus G protein

The cellular immune response to respiratory syncytial virus (RSV) is important in both protection and immunopathogenesis. In contrast to HLA class I, HLA class II-restricted RSV-specific T-cell epitopes have not been identified. Here, we describe the generation and characterization of two human RSV-specific CD4(+)-T-cell clones (TCCs) associated with type 0-like cytokine profiles. TCC 1 was specific for the matrix protein and restricted over HLA-DPB1*1601, while TCC 2 was specific for the attachment protein G and restricted over either HLA-DPB1*0401 or -0402. Interestingly, the latter epitope is conserved in both RSV type A and B viruses. Given the high allele frequencies of HLA-DPB1*0401 and -0402 worldwide, this epitope could be widely recognized and boosted by recurrent RSV infections. Indeed, peptide stimulation of peripheral blood mononuclear cells from healthy adults resulted in the detection of specific responses in 8 of 13 donors. Additional G-specific TCCs were generated from three of these cultures, which recognized the identical (n = 2) or almost identical (n = 1) HLA-DP4-restricted epitope as TCC 2. No significant differences were found between the capacities of cell lines obtained from infants with severe (n = 41) or mild (n = 46) RSV lower respiratory tract infections to function as antigen-presenting cells to the G-specific TCCs, suggesting that the severity of RSV disease is not linked to the allelic frequency of HLA-DP4. In conclusion, we have identified an RSV G-specific human T helper cell epitope restricted by the widely expressed HLA class II alleles DPB1*0401 and -0402. Its putative role in protection and/or immunopathogenesis remains to be determined

Respiratory syncytial virus specific serum antibodies in infants under six months of age: limited serological response upon infection.

The decline of maternal respiratory syncytial virus (RSV) specific serum antibodies was studied in 45 children during the first 6 months of life, using a virus neutralization assay and competition ELISAs measuring fusion protein and glycoprotein specific antibodies. In all children RSV neutralizing antibodies were demonstrated at birth, with titers ranging from 33 to 1382. The calculated mean half life of these antibodies was 26 days. Furthermore, in a group of 38 children with suspected RSV infection, all younger than 6 months of age on admission, the diagnostic value of serological assays was evaluated. In 32 children RSV infection was confirmed by virus isolation, direct immune fluorescence and RT-PCR. In 7 patients of this group a significant titer rise in virus neutralization assay was demonstrated. Six additional RSV infected children could be identified by showing the presence of RSV-specific IgM or IgA serum antibodies or by showing an increase in fusion protein or glycoprotein specific antibodies. All serological tests together identified 13 (41%) of the 32 RSV infected patients. It is concluded that in children of this age group, which represent the majority of patients hospitalized with RSV infections, serological assays not only have a limited diagnostic value but are of limited value for sero-epidemiological studies