Difference in respiratory syncytial virus-specific Fc-mediated antibody effector functions between children and adults

Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of these functional responses. In light of future vaccine strategies, a clear view of the immunological background and differences between various target populations is of crucial importance. In this study, we have assessed both quantitative and qualitative aspects of RSV-specific serum antibodies, including IgG/IgA levels, IgG subclasses, antibody-dependent complement deposition, cellular phagocytosis, and NK cell activation (ADNKA). Samples were collected cross-sectionally in different age groups (11-, 24-, and 46-month-old children, adults, and older adults; n = 31–35 per group) and longitudinally following natural RSV infection in (older) adults (2–36 months post-infection; n = 10). We found that serum of 24-month-old children induces significantly lower ADNKA than the serum of adults (P < 0.01), which is not explained by antibody levels. Furthermore, in (older) adults we observed boosting of antibody levels and functionality at 2–3 months after RSV infection, except for ADNKA. The strongest decrease was subsequently observed within the first 9 months, after which levels remained relatively stable up to three years post-infection. Together, these data provide a comprehensive overview of the functional landscape of RSV-specific serum antibodies in the human population, highlighting that while antibodies reach adult levels already at a young age, ADNKA requires more time to fully develop

Asthma-Associated Long TSLP Inhibits the Production of IgA.

Thymic stromal lymphopoietin (TSLP) contributes to asthmatic disease. The concentrations of protective IgA may be reduced in the respiratory tract of asthma patients. We investigated how homeostatic short TSLP (shTSLP) and asthma‐associated long TSLP (loTSLP) regulate IgA production. B cells from healthy donors were stimulated in the presence or absence of shTSLP or loTSLP; the concentrations of IgA, IgM, IgE, and IgG antibodies were determined in cell culture supernatants; and B cells were analyzed by flow cytometry. LoTSLP, but not shTSLP, suppressed the secretion of IgA but not of IgE. The type 2 cytokine IL‐4, which in addition to loTSLP contributes to asthmatic disease, did not affect the production of IgA or the frequency of IgA+ B cells. Instead, IL‐4 increased IgG production, especially of the subclasses IgG2 and IgG4. LoTSLP inhibited IgA secretion by sorted memory B cells but not by naïve B cells. Although loTSLP inhibited IgA production, the vitamin A metabolite retinoic acid promoted the secretion of IgA, also in the presence of loTSLP, suggesting that vitamin A may promote IgA production in asthma. Our data demonstrate that asthma‐associated loTSLP negatively regulates the secretion of IgA, which may negatively impact the surveillance of mucosal surfaces in asthm

Mumps outbreak in a highly vaccinated student population, The Netherlands, 2004

In September 2004 a mumps outbreak occurred at an international hotel school in The Netherlands. We investigated this outbreak to identify risk factors for mumps. There were 105 mumps cases (overall mumps attack rate (AR) 12% (95% CI: 10-15%)). The AR for Dutch vaccinated and unvaccinated participants was 12% (95% CI: 10-15%) and 15% (95% CI: 3-42%), respectively. Independent risk factor was mumps contact. Explanations for the relatively high AR among vaccinated participants include primary vaccine failure, waning immunity and incomplete vaccine-induced immunity in the context of high mumps virus exposure in a school party and a crowded boarding schoo