Our data suggest that B19V but not HBoV demonstrates a lifelong persistence in the heart. The detection of B19V DNA in heart tissue showed no correlation with clinical symptoms. We strongly recommend that serological testing become a standardized procedure for future studies, to obtain representative data concerning the prevalence of B19V in the heart.

Statement of Translational RelevanceSurvival rates for patients with glioblastoma (GBM) are abysmal, with median overall survival of approximately 15 months. Immunotherapy of GBM is a promising area of investigation, although challenges around identification of novel and immunogenic target antigens exist. IMA950 is a GBM specific vaccine comprising 11 tumor-associated peptides (TUMAPs) developed to address this challenge. We have performed a phase 1 safety and immunogenicity study in newly diagnosed GBM patients using IMA950 plus GM-CSF alongside standard of care chemo-radiotherapy. Our results demonstrate that IMA950 is well tolerated with 90% of patients having a CD8+ T-cell immune response to at least one TUMAP, with 50% responding to two or more TUMAPs. No effect of pre-treatment regulatory T-cell levels on IMA950 immunogenicity was found and steroids did not appear to affect immune responses to the TUMAPs. This data provides evidence to support further development and optimization of IMA950 together with other immunotherapies for GBM. were multi-TUMAP responders, with no important differences between cohorts. No effect of pre-treatment Treg levels on IMA950 immunogenicity was observed and steroids did not affect TUMAP responses. PFS was 74% at 6 months and 31% at 9 months. CONCLUSION: IMA950 plus GM-CSF was well tolerated with the primary immunogenicity endpoint of observing multi-TUMAP responses in at least 30% of patients exceeded.Further development of IMA950 is encouraged.

Human bocavirus (HBoV) was recently detected in samples from children and infants with infections of the respiratory tract. Here we analyze the prevalence of IgG and IgM antibodies against HBoV virus-like VP2 particles in healthy adult blood donors and children using a newly established standardized enzyme-linked immunosorbent assay. Virus-specific IgG antibodies were frequently detected in infants with active viremia and respiratory illness (10/24, 42%) and in young children without detectable HBoV genomes in their blood (27/52, 52%). In sera obtained from healthy adults, ubiquitous VP2-specific antibodies were found in 280/299 (94%) cases. HBoV-specific IgM antibodies were detected in 10/24 (42%) of sera samples obtained from HBoV DNA-positive children, and in 6/24 (25%) the sera displayed equivocal responses. In contrast, VP2-specific IgM was not detectable in samples obtained from 52 children without detectable amounts of HBoV genomes in their blood. Only 2/299 sera samples from healthy adult blood donors were found to be IgM-positive (1%), and equivocal IgM responses were observed in 9/299 (3%) individuals. In conclusion, a high IgG seroprevalence of HBoV in the adult population was observed, whereas the presence of virus-specific IgM was associated with viremia. These data show that ELISA test systems for the detection of HBoV-specific antibodies are a valuable tool for serological diagnosis of this new emerging pathogen.

Human bocavirus (HBoV) was recently described as a new member of the Parvoviridae. In order to investigate the suggested association of HBoV with respiratory and gastric disease in infants and young children, sera of 357 paediatric patients hospitalized with infectious and non-infectious diseases were retrospectively analyzed for the presence of HBoV DNA and virus-specific antibodies using quantitative PCR and ELISA, respectively. HBoV seroprevalence was determined to range from 25% in infants younger than 1 year of age to 93% in children aged more than 3 years. Viral loads between 1 x 10(2) and 1.2 x 10(6) geq/mL were observed in 6.7% (20/297) of sera obtained preferentially from young children suffering from infectious diseases. HBoV genomes were furthermore detected in 5% (3/60) of sera collected from individuals with non-infectious illnesses. HBoV DNA was present most frequently in patients with respiratory disease (9.6%). Whereas only 5.2% of patients with upper respiratory tract disease were viraemic, HBoV DNA was found in 14.6% and 10.0% of patients with lower respiratory tract illness and pneumonia, respectively. Acute HBoV infections were also observed in 7.5% of patients with gastroenteritis and in one child with inflammatory bowel disease. None of 77 patients hospitalized for various other infectious diseases (e.g. rash, urinary tract infection, meningitis) displayed viraemia. In 60.9% and 47.8% of DNA-positive children, HBoV-specific IgM and IgG was observed, respectively. The present prospective study provides comprehensive data on the clinical association of acute HBoV infection with respiratory illness and on the seroprevalence of virus-specific antibodies in children.

For almost three decades parvovirus B19 has been described as the only member of the Parvoviridae to infect and cause illness in humans. This statement was correct until 2005 when a group of Swedish scientists identified a previously uncharacterized virus in pools of human nasopharyngeal aspirates obtained from individuals suffering from diseases of the respiratory tract. Comprehensive sequence and phylogenetic analysis allowed the identification of the new virus as a member of the Parvoviridae. Based on its close relation to the minute virus of canines and the bovine parvovirus, it was named human bocavirus (HBoV). Since the identification of HBoV, viral genomes have been frequently detected worldwide in nasopharyngeal swabs, serum and fecal samples almost exclusively derived from young children with various symptoms of the respiratory or the gastrointestinal tract. The detection of HBoV genomes tends to be associated with elevated rates of coinfections with further respiratory viruses, e.g. respiratory syncytial virus or metapneumovirus. First studies on virus-specific immune responses have described the presence of ubiquitous humoral and cellular immune reactions against HBoV in adults and adolescents, indicating a high seroprevalence of this new virus in humans.

Data suggest the presence of HBoV-specific immune responses in adults and strongly support a high prevalence of HBoV among humans.

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