Biomedical subjects

Alois B Lang

Publications and source records attributed to Alois B Lang.

7 recordsLinked to original sources

PubMed2006

Intranasal immunisation with conjugate vaccine protects mice from systemic and respiratory tract infection with Pseudomonas aeruginosa.

We tested intranasal application of anti-Pseudomonas conjugate vaccine in mice. Comparison of immunisation via the intra-muscular versus intranasal routes showed the induction of equivalent levels of specific serum IgG and IgG subclasses antibodies if cholera toxin was used as an adjuvant. In contrast, secretion of specific mucosal IgA antibodies in the upper respiratory tract was only observed after intranasal immunisation together with adjuvant. Systemic and mucosal immunity was also established via the intranasal route when CpG-containing oligonucleotides were used as adjuvant. The functionality of intranasally induced antibodies was proven in vitro by opsonophagocytosis and in vivo using the burn-wound sepsis and intra-tracheal lung infection models. These results demonstrate the feasibility of intranasal immunisation against P. aeruginosa with conjugate vaccine.

Administration, Intranasal↗

PubMed2006

Antibody responses induced by long-term vaccination with an octovalent conjugate Pseudomonas aeruginosa vaccine in children with cystic fibrosis.

We assessed the serological responses over 10 years to repeated immunization of cystic fibrosis (CF) patients with an O-polysaccharide (OPS)-toxin A conjugate vaccine against Pseudomonas aeruginosa. A retrospective analysis was performed with sera from 25 vaccinated and 25 unvaccinated children treated at the same CF centre and matched for clinical management, age and gender. Yearly immunization led to sustained elevations of serum immunoglobulin G (IgG) antibody levels to all vaccine components. Eighteen unvaccinated patients but only eight vaccinated ones developed chronic pseudomonal lung infections. Infection rapidly caused further marked elevations of polysaccharide- but not toxin A-specific serum IgG in both immunized and nonimmunized patients, indicating that protection did not depend on the quantity of IgG present. However, qualitative analyses revealed that the protective capacity of specific serum IgG antibodies was linked to high affinity and to specificity for OPS serotypes rather than for lipopolysaccharide core epitopes.

Adolescent↗

PubMed2004

Prophylaxis and therapy of Pseudomonas aeruginosa infection in cystic fibrosis and immunocompromised patients.

Pseudomonas aeruginosa is an opportunistic bacterium responsible for chronic lung infection in cystic fibrosis patients, as well as nosocomial infections in immunocompromised patients. An O-polysaccharide-toxin A conjugate vaccine was evaluated for prophylaxis of P. aeruginosa in cystic fibrosis patients. Vaccination proved to be useful in preventing and/or delaying infection. Fully human monoclonal antibodies (mAb) against P. aeruginosa O-polysaccharides were developed for the treatment of immunocompromised patients in whom active immunoprophylaxis is not applicable. Characterisation of the mAb revealed high antigen specificity and avidity, as well as excellent efficacy in relevant in vitro and in vivo systems, permitting future clinical evaluation.

Animals↗

PubMed2004

B cells alter the phenotype and function of follicular-homing CXCR5+ T cells.

The CXC chemokine receptor (CXCR)5 is rapidly induced on activated CD4(+) T cells, allowing migration toward secondary lymphoid tissue follicles, where the CXCR5 ligand CXCL13/BCA-1 is produced. Such CXCR5(+) T cells provide efficient help for B cell immunoglobulin production and are termed follicular B helper T (T(FH)) cells. However, the molecular mechanisms by which T(FH) cells provide B cell help are unknown. Here, we demonstrate that newly generated (antigen-primed) T(FH) cells express a phenotype consistent with induction of B cell proliferation, but co-culture with primed B cells resulted in a switch to a plasma cell-inducing phenotype, characterized by loss of CD154, induction of CD70 and an increase in IL-10 production capacity. The ability to produce IL-10 could be maintained as a stable phenotype, but its secretion was strictly dependent on inducible costimulator (ICOS) signaling. Furthermore, B cells preserved a lymph node migration phenotype in proliferating T(FH) cells by preventing the loss of CC chemokine receptor (CCR)7 and the induction of CCR5. Thus, B cells directly modulate the B cell helper phenotype in T(FH) cells and actively promote their prolonged co-localization with these cells.

Antibody Formation↗

PubMed2004

Vaccination of cystic fibrosis patients against Pseudomonas aeruginosa reduces the proportion of patients infected and delays time to infection.

INTRODUCTION: Cystic fibrosis (CF) almost always leads to chronic airway infection with Pseudomonas aeruginosa. Despite advances in antibiotic therapy, after chronic infection rapid deterioration in lung function occurs, increasing morbidity and mortality. Prevention of infection by vaccination is desirable, but earlier trials produced disappointing results. The promising short term immunogenicity and safety of a new P. aeruginosa vaccine prompted us to evaluate its long term efficacy. We conducted a 10-year retrospective analysis of outcomes in a group of vaccinated patients. MATERIALS AND METHODS: In 1989-1990, 30 young children with CF, mean age 7 years, with no prior history of infection with P. aeruginosa, were vaccinated against P. aeruginosa with a polyvalent conjugate vaccine. We report the follow-up of 26 of these patients from 1989 to 2001. The patients were given yearly vaccine boosters. Comparisons were made with a CF patient control group matched for gender, age and, where possible, genetic mutation. Vaccinated patients and controls were attending a single CF clinic and received the same clinical management throughout the study period. Main outcomes were time to infection, proportion of patients infected, development of P. aeruginosa mucoid phenotype, lung function and body weight. RESULTS: The time to infection with P. aeruginosa was longer in the vaccination group than in the control group, and fewer vaccinated patients than controls became chronically infected (32% versus 72%; P < 0.001). The proportion of mucoid infections was higher in the control group (44%) than in the vaccinated group (25%). Patients >/=18 years of age at the end of the study had a lower mean forced expiratory volume at 1 s (FEV1) than did those 13-17 years of age, but this difference was small in the vaccinated group (73.6% versus 83.7%) compared with the controls (48.0% versus 78.7%). In the >/=18 year age category the mean FEV1% at 10 years was 73.6% (vaccinated) and 48.0% (controls) (P < 0.05). In the vaccinated group only 11 (44%) of 25 patients were underweight at the 10-year follow-up compared with 18 (72%) of 25 at the beginning of the study. In the control group 17 (68%) of 25 patients were underweight at 10-year follow-up compared with 16 (64%) of 25 at the beginning of the study. CONCLUSION: Regular vaccination of young CF patients for a period of 10 years with a polyvalent conjugate vaccine reduced the frequency of chronic infection with P. aeruginosa. This was associated with better preservation of lung function. Vaccinated patients gained more weight during the study period, a possible indication of an improved overall health status.

Adolescent↗

PubMed2003

Flexible migration program regulates gamma delta T-cell involvement in humoral immunity.

gamma delta T cells are inadequately defined both in terms of their migration potential and contribution to antimicrobial immunity. Here, we have examined the migration profile of human blood gamma delta T cells and related cell lines and correlated these findings with their distribution in secondary lymphoid tissues and their function in B-cell cocultures. We find that resting gamma delta T cells are characterized by an inflammatory migration program similar to cells of the innate immune system. However, T-cell receptor (TCR) triggering resulted in the rapid but transient induction of a lymph node (LN)-homing program, as evidenced by functional CCR7 expression and concomitant reduction in expression and function of CCR5 and, to a lesser degree, CCR2. Moreover, the LN-homing program was reflected by the presence of gamma delta T cells in gastrointestinal lymphoid tissues, notably in clusters within germinal centers of B-cell follicles. In line with these findings, V gamma V delta-TCR triggering resulted in prominent expression of essential B-cell costimulatory molecules, including CD40L, OX40, CD70, and ICOS. Furthermore, gamma delta T cells were shown to provide potent B-cell help during in vitro antibody production. Collectively, our findings agree with a role for gamma delta T cells in humoral immunity during the early phase of antimicrobial responses.

Antibody Formation↗

PubMed2003

Experience with registered mucosal vaccines.

Most pathogens gain access to their host through mucosal surfaces. It is therefore desirable to develop vaccination strategies that lead to mucosal immune responses. Ideally, a vaccine should be administered mucosally in order to elicit mucosal protection. Several attenuated live viral and bacterial pathogens are registered as oral vaccines for human use, including the oral polio vaccine (Sabin) as well as attenuated strains of Salmonella typhi and Vibrio cholerae. These attenuated bacterial live vaccines-S. typhi Ty21a as well as V. cholerae CVD 103-HgR-are employed as vaccines against typhoid and cholera, respectively. In this manuscript, we review the immune responses that are induced by these vaccines, with a focus on mucosal immunity.

Administration, Oral↗