High Seroprevalence of Neutralizing Capacity against Human Metapneumovirus in All Age Groups Studied in Bonn, Germany

Lüsebrink, Jessica; Wiese, C.H.R.; Thiel, Anne; Tillmann, Ramona-Liza; Ditt, Vanessa; Müller, Andreas; Schildgen, Oliver; Schildgen, Verena

doi:10.1128/cvi.00398-09

Cited by 31 publications

(24 citation statements)

References 22 publications

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“…The first HMPV infection appears to take place at 6 months of life, after which infections may occur repeatedly and frequently. The elderly represent the second group of patients that are severely affected by HMPV, and severe HMPV infections in the elderly occur despite high seroprevalence rates and independent of immunosenescence (62,153). Reports on HMPV infections in otherwise healthy adults are relatively rare.…”

Section: Clinical Epidemiologymentioning

confidence: 99%

“…Reports on HMPV infections in otherwise healthy adults are relatively rare. Seroprevalence studies indicated that all adults have been infected with HMPV by the age of 25, with very high seroprevalence rates beginning from 5 years of age (68,147,150,153,255,261,262). The nosocomial impact of HMPV is estimated to be as high as that for RSV.…”

Section: Clinical Epidemiologymentioning

confidence: 99%

See 1 more Smart Citation

Human Metapneumovirus: Lessons Learned over the First Decade

Schildgen

Hoogen²,

Fouchier³

et al. 2011

Clin Microbiol Rev

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186

187

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SUMMARY It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future.

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Section: Clinical Epidemiologymentioning

confidence: 99%

Section: Clinical Epidemiologymentioning

confidence: 99%

Human Metapneumovirus: Lessons Learned over the First Decade

Schildgen

Hoogen²,

Fouchier³

et al. 2011

Clin Microbiol Rev

Self Cite

186

187

View full text Add to dashboard Cite

show abstract

“…Mice are semipermissive hosts for HMPV, and wild-type B6 mice cannot be reinfected with HMPV, whereas reinfections in humans are common (11,12,41). For this reason, we performed additional experiments in MT mice, which lack mature B cells and can be reinfected with HMPV.…”

Section: Cells (E and F) Expression Of Pd-1 (E) And Other Inhibitorymentioning

confidence: 99%

Lung CD8⁺T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8⁺T Cells

Wen

Schuster

Gilchuk

et al. 2015

J Virol

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Human metapneumovirus (HMPV) is a major cause of respiratory disease in infants, the elderly, and immunocompromised individuals worldwide. There is currently no licensed HMPV vaccine. Virus-like particles (VLPs) are an attractive vaccine candidate because they are noninfectious and elicit a neutralizing antibody response. However, studies show that serum neutralizing antibodies are insufficient for complete protection against reinfection and that adaptive T cell immunity is important for viral clearance. HMPV and other respiratory viruses induce lung CD8 ؉ T cell (T CD8 ) impairment, mediated by programmed death 1 (PD-1). In this study, we generated HMPV VLPs by expressing the fusion and matrix proteins in mammalian cells and tested whether VLP immunization induces functional HMPV-specific T CD8 responses in mice. C57BL/6 mice vaccinated twice with VLPs and subsequently challenged with HMPV were protected from lung viral replication for at least 20 weeks postimmunization. A single VLP dose elicited F-and M-specific lung T CD8 s with higher function and lower expression of PD-1 and other inhibitory receptors than T CD8 s from HMPV-infected mice. However, after HMPV challenge, lung T CD8 s from VLP-vaccinated mice exhibited inhibitory receptor expression and functional impairment similar to those of mice experiencing secondary infection. HMPV challenge of VLP-immunized MT mice also elicited a large percentage of impaired lung T CD8 s, similar to mice experiencing secondary infection. Together, these results indicate that VLPs are a promising vaccine candidate but do not prevent lung T CD8 impairment upon HMPV challenge. IMPORTANCEHuman metapneumovirus (HMPV) is a leading cause of acute respiratory disease for which there is no licensed vaccine. Viruslike particles (VLPs) are an attractive vaccine candidate and induce antibodies, but T cell responses are less defined. Moreover, HMPV and other respiratory viruses induce lung CD8 ؉ T cell (T CD8 ) impairment mediated by programmed death 1 (PD-1). In this study, HMPV VLPs containing viral fusion and matrix proteins elicited epitope-specific T CD8 s that were functional with low PD-1 expression. Two VLP doses conferred sterilizing immunity in C57BL/6 mice and facilitated HMPV clearance in antibodydeficient MT mice without enhancing lung pathology. However, regardless of whether responding lung T CD8 s had previously encountered HMPV antigens in the context of VLPs or virus, similar proportions were impaired and expressed comparable levels of PD-1 upon viral challenge. These results suggest that VLPs are a promising vaccine candidate but do not prevent lung T CD8 impairment upon HMPV challenge. in 2001 (1, 2). The virus is a major cause of acute respiratory morbidity and mortality in infants, older adults, and immunocompromised individuals, although serological studies indicate that almost all humans have been infected by 5 years of age (2, 3). There are four subtypes of HMPV classified by genotype: A1, A2, B1, and B2 (4). The fusion (F) protein, which mediates ...

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“…Almost all people acquire seropositivity for hMPV by the age of 10 years, 2 and hMPV is known to infect individuals repeatedly throughout adult life and into old age. [5][6][7][8][9] Although there are no reports of IgG titer differences between patients with hypertension and normotensive controls after individual infections with pathogens, including hMPV, it is possible that hypertension itself may increase the anti-IgG titer in response to repeated hMPV infections in the elderly. In this present cross-sectional study, however, we could not show any time-course data for anti-hMPV-IgG titers in individual subjects.…”

Section: Discussionmentioning

confidence: 99%

“…This finding suggests that reinfection occurs because humoral immune responses have a minor role in the clearance of hMPV. 9 However, the relationship between hMPV infection and the underlying chronic clinical conditions has not been adequately evaluated in elderly subjects. Therefore, the aim of this study was to determine the relationship between the titer of immunoglobulin (Ig) G antibody against hMPV (anti-hMPV-IgG titer) and clinical conditions, including hypertension, in elderly patients in a Japanese LTCF.…”

Section: Introductionmentioning

confidence: 99%

Association between human metapneumovirus seroprevalence and hypertension in elderly subjects in a long-term care facility

et al. 2011

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Recently, relations between hypertension and infections caused by several pathogens have been reported. However, few studies have examined the relationship between human metapneumovirus (hMPV) and hypertension in elderly inpatients. To assess the association between anti-hMPV-immunoglobulin G (IgG) titer and the prevalence of hypertension, we conducted a case-control study in a Japanese long-term care facility (LTCF). The participants included 84 hypertensive patients aged X65 years, and 84 age-and sex-matched normotensive controls (38 males and 46 females in each group; cases, 79.9 ± 8.4 (s.d.) years; controls, 80.1 ± 8.3 years). Data on underling chronic clinical conditions were collected. Titers were measured using an immunofluorescence assay kit. The significance of risk factor differences was analyzed using univariate and multivariate comparisons of cases and controls. All serum samples were positive for hMPV, and IgG titers ranged from 40-fold to more than 5120-fold. There were no significant sex-or age-related differences in log 2 (anti-hMPV-IgG titer/10) among the subjects. Compared with normotensive subjects, hypertensive patients presented significantly higher log 2 (anti-hMPV-IgG titer/10) values (Po0.001). After adjustment with multiple logistic analysis, the odds ratio for log 2 (anti-hMPV-IgG titer/10) was 1.42 (95% confidence interval 1.16-1.75, P¼0.001) relative to normotensive subjects. In all subjects, stepwise multiple regression analysis revealed that both hypertension and a poor nutritional state independently contributed to increased log 2 (anti-hMPV-IgG titer/10). These observations suggest that an increased anti-hMPV-IgG titer was closely related to hypertension in elderly subjects in a Japanese LTCF.

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High Seroprevalence of Neutralizing Capacity against Human Metapneumovirus in All Age Groups Studied in Bonn, Germany

Cited by 31 publications

References 22 publications

Human Metapneumovirus: Lessons Learned over the First Decade

Human Metapneumovirus: Lessons Learned over the First Decade

Lung CD8⁺T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8⁺T Cells

Association between human metapneumovirus seroprevalence and hypertension in elderly subjects in a long-term care facility

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High Seroprevalence of Neutralizing Capacity against Human Metapneumovirus in All Age Groups Studied in Bonn, Germany

Cited by 31 publications

References 22 publications

Human Metapneumovirus: Lessons Learned over the First Decade

Human Metapneumovirus: Lessons Learned over the First Decade

Lung CD8+T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8+T Cells

Association between human metapneumovirus seroprevalence and hypertension in elderly subjects in a long-term care facility

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Lung CD8⁺T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8⁺T Cells