Markus A. Rose

Efficacy of probiotic Lactobacillus GG on allergic sensitization and asthma in infants at risk

Background Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases.

Mucosal immunity and nasal influenza vaccination

Influenza remains a threat to public health, with immunization being a suitable method of infection prevention and control. Our understanding of the immunological regulations at the mucosa, antigen processing and presentation, and B-cell activation has improved, enabling research and targeted induction of immune responses at the site of antigen delivery. Nasal influenza immunization has distinct features compared with intramuscular vaccines, providing protection at the pathogen’s entry site, higher levels of mucosal antibodies, cross-protection and needle-free application. This review summarizes our knowledge about mucosal immunity and the experience from clinical trials on the impact and safety of nasal influenza vaccination.

Effect of n–3 Polyunsaturated Fatty Acids in Asthma after Low-Dose Allergen Challenge

Background: We investigated the anti-inflammatory potential of n–3 polyunsaturated fatty acids (PUFA) on specific bronchial inflammation. Allergic asthmatics were challenged using a low-dose allergen provocation model. Methods: Our parallel double-blinded study randomly assigned 23 house dust mite-allergic asthmatics (aged 22–29 years; 13 females, 10 males) to dietary supplementation with either an n–3 PUFA-enriched fat blend (0.69 g/day) or placebo for 5 weeks. After 3 weeks, the patients were challenged daily with low doses of mite allergen for 2 weeks. Primary outcome parameters were effects on lung function (forced expiratory volume in 1 s, FEV1) and exhaled nitric oxide (eNO) as a marker of bronchial inflammation. Results: Even before the bronchial challenge, eNO was significantly lower in the n–3 PUFA group (p = 0.014). Levels of eNO increased during allergen exposure in both groups, but differences in means were significantly lower in the n–3 PUFA group (p = 0.022). During the low-dose allergen challenge, there were no differences between the groups with regard to symptoms, FEV1 or the allergen dose required to induce deterioration of lung function (PD20). Numbers of sputum eosinophils did not differ significantly, while serum eosinophils (10.1 ± 0.1.84 vs. 5.79 ± 0.69%) as well as changes in eosinophilic cationic protein (20.5 ± 9.93 vs. –1.68 ± 4.36 ng/ml) and in vitro cysteinyl leukotriene release (2,889 ± 872 vs. 1,120 ± 173 ng/ml) were significantly lower in the n–3 PUFA group (p < 0.05 each). Conclusion: Our results provide evidence that dietary supplementation with n–3 PUFA is able to reduce bronchial inflammation even after low-dose allergen challenge.

Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects

In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost-effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease.

Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children.

Specific immunotherapy (SIT) is a well‐established and clinically effective treatment for allergic diseases. A pollen allergoid formulated with the T helper type 1 (Th1)‐inducing adjuvant monophosphoryl lipid A (MPL) facilitates short‐term SIT. Little is known about mechanisms of tolerance induction in this setting. In a prospective study, 34 patients allergic to grass pollen (25 male, nine female, median age 10·2 years) received a total of 44 SIT courses (20 in the first, 24 in the second) with MPL‐adjuvanted pollen allergoids. Immunogenicity was measured by levels of specific immunoglobulin G (IgGgrass) and IgG4grass by antibody blocking properties on basophil activation, and by induction of CD4+, CD25+ and forkhead box P3 (FoxP3+) regulatory T cells (Treg). Specific IgG and IgG4 levels increased only slightly in the first year of SIT. In the second year these changes reached significance (P < 0·0001). In keeping with these findings, we were able to show an increase of Treg cells and a decreased release of leukotrienes after the second year of treatment. In the first year of treatment we found little evidence for immunological changes. A significant antibody induction was seen only after the second course of SIT. Short‐course immunotherapy with pollen allergoids formulated with the Th1‐inducing adjuvant MPL needs at least two courses to establish tolerance.

Priming of Immunological Memory by Pneumococcal Conjugate Vaccine in Children Unresponsive to 23-Valent Polysaccharide Pneumococcal Vaccine

ABSTRACT Pneumococcal polysaccharide vaccine (PPV) is of limited immunogenicity in infants and immunocompromised patients. Our prospective randomized controlled trial investigated whether priming with pneumococcal conjugate vaccine (PCV) induced specific immunological memory in previously nonresponders to PPV. Of a total of 33 children (2 to 18 years) with polysaccharide-specific immunodeficiency (PSI), group A (n = 16) received two doses of 7-valent PCV in a 4- to 6-week interval, and a booster dose of 23-valent PPV after one year. Group B (n = 17) received two doses of PPV in a 1-year interval exclusively. Specific antibody concentrations for serotypes 4, 5, 6B, 9V, 14, 18C, 19F, and 23F were determined (enzyme-linked immunosorbent assay) before and at 7 and 28 days after administration of the PPV booster and compared to an opsonophagocytosis assay. Of group A, 64 to 100% had antibody concentrations of ≥1 μg/ml on day 28 after the booster versus 25 to 94% of group B. Group A had significantly higher antibody concentrations for all PCV-containing serotypes already on day 7, indicating early memory response. Antibody concentrations were in accordance with functional opsonic activity, although opsonic titers varied among individuals. Pneumococcal vaccination was well tolerated. The incidence of airway infections was reduced after priming with PCV (10/year for group A versus 15/year for group B). Following a PPV booster, even patients primarily not responding to PPV showed a rapid and more pronounced memory response after priming with PCV.

Rotavirus vaccines: considerations for successful implementation in Europe

A group of European experts in infectious diseases and vaccinology has met on several occasions to assess the rationale for universal vaccination against rotavirus infection of infants in Europe. On the basis of the available data, we concluded that vaccination was the best approach to prevent severe rotavirus gastroenteritis, and that European countries should consider implementing rotavirus vaccination in their routine immunisation programmes. The main barrier to the implementation of rotavirus vaccination in Europe is a general lack of awareness of stakeholders, policymakers, health-care professionals, and parents about rotavirus disease and the advantages of vaccination. Further studies on the cost of the disease and the benefit of vaccination, together with raising awareness are necessary steps to ensure successful implementation of rotavirus vaccination in Europe.

Systemic and bronchial inflammation following LPS inhalation in asthmatic and healthy subjects

Background: Inhaled endotoxin is known to induce airway inflammation, causing bronchial hyper-reactivity. Objective: We characterized the response to lipopolysaccharide-inhalation by measuring exhaled nitric oxide (eNO) and inflammatory mediators. Patients and Methods : A total of 43 adult volunteers (13 asthmatics, 30 healthy controls) inhaled stepwise LPS every 30 min up to a cumulative dose of 100 µg (2.5, 10.5, 42, 45 µg). After each provocation and up to 24 h later, FEV1 was determined; the procedure was stopped when FEV1 declined more than 12.5%. We measured eNO, leucocytes, eosinophils, polymorphonuclear neutrophils (PMNs), C-reactive protein (CrP), lipopolysaccharide binding protein (LBP), eosinophilic cationic protein (ECP), leucotriene B4 (LTB4), thromboxane B2 (TXB2), and body temperature. Results: Initial eNO values were higher in asthmatics (P < 0.01), but only increased in an asthmatic subgroup. Marked differences were observed in the systemic response to LPS inhalation. Significant increases were found for CrP, LBP, and PMNs. There was no correlation between FEV1 decrease and basal eNO levels. Conclusions: Inhalation of endotoxin was followed by clinical and laboratory signs of systemic inflammation, with asthmatics responding to the challenge similar as healthy subjects. Bronchial eNO increased only temporarily in asthmatics.

Health care providers’ and parents’ attitudes toward administration of new infant vaccines—a multinational survey

The New Vaccinations of Infants in Practice online survey in seven countries evaluated vaccination-related attitudes and concerns of parents of infants and health care providers (HCPs) who provide pediatric medical care. The survey showed that HCPs and parents were open to adding new vaccines to the immunization schedule, even if it requires co-administration with current vaccines or introduction of new office visits. Parental disease awareness campaigns would be helpful to achieve widespread acceptance of changes to vaccination schedules. In addition, HCPs would ideally provide disease education to parents to accompany recommendations for a new vaccine.

Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.

Background: Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. Methods: A total of 34 children (6–18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgGMite and IgG4Mite, by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. Results: There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgGMite (p < 0.001) and specific IgG4Mite (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. Conclusion: Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients.