Search PubMed⌕ Search

Biomedical subjects

Adam Finn

Publications and source records attributed to Adam Finn.

At least 19 recordsLinked to original sources
PubMed2006

Serum and mucosal antibody responses to pneumococcal protein antigens in children: relationships with carriage status.

Streptococcus pneumoniae causes significant morbidity and mortality especially in children. Some pneumococcal protein antigens can protect mice against infection. Little information is available concerning the nature of naturally acquired protective immunity to pneumococci in humans induced by these antigens. This study investigates the relationships between systemic and local antibody production and carriage in children. Children undergoing adenoidectomy (n=112, ages 2-12 years) were studied. Nasopharyngeal swabs were collected for pneumococcal culture. Serum and saliva were assayed for antibodies to several pneumococcal proteins: choline binding protein A (CbpA), pneumolysin (Ply), pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA). Adenoidal mononuclear cells (MNC) were cultured with pneumococcal culture supernatants or recombinant proteins. Cell culture supernatants were analyzed for antigen-specific antibodies. Carriage rates fell with age and serum levels of anti-CbpA, Ply and PspA rose. Anti-CbpA and -Ply serum and salivary IgG antibody levels were higher in children who were culture negative than those who were colonized. Antigen stimulation increased respective antigen-specific IgG production by adenoidal MNC and these responses were greater in those who were colonized than in culture-negative children. Antibodies to CbpA and Ply may protect children aged 2 years and older against pneumococcal colonization. Adenoids may be important local induction and effector sites for both mucosal and systemic antibody production to pneumococcal proteins in children.

Adenoids↗
PubMed2006

Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy.

Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp(299)Gly and Thr(399)Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.

Age Factors↗
PubMed2006

Childhood empyema: limited potential impact of 7-valent pneumococcal conjugate vaccine.

During 2003-2004, locally presenting pleural empyema cases in children increased 3-fold. Antigen analysis of empyema fluid identified Streptococcus pneumoniae in 27 of 29 cases for whom samples were available and capsular polysaccharide type 1 in 18 of these. Use of a conjugate vaccine without serotype 1 antigen would have had limited impact on this morbidity in our region.

Age Distribution↗
PubMed2006

Regulation of production of mucosal antibody to pneumococcal protein antigens by T-cell-derived gamma interferon and interleukin-10 in children.

Nasopharyngeal tonsils (adenoids) are part of human nasopharynx-associated lymphoid tissue, which may play an important role in local defense against pneumococci. Recent studies with animals have suggested that several pneumococcal proteins, including CbpA and pneumolysin (Ply), may be vaccine candidates. Our recent data obtained with children suggest that antibodies to these proteins may protect against carriage. This study was performed to investigate the regulation of the T-cell-dependent antibody responses to CbpA and pneumolysin by cytokines in adenoidal immune cells from children. Adenoidal mononuclear cells (MNC) were cultured with pneumococcal concentrated culture supernatants (CCS) or recombinant proteins. Cytokine expression profiles in adenoidal MNC after antigen stimulation were analyzed by reverse transcription-PCR, protein array analysis, and an immunoassay, along with an antibody production analysis. The roles, interactions, and cellular sources of the main cytokines identified were evaluated further. Pneumococcal CCS induced production of CbpA- and Ply-specific antibodies in association with several chemokines and cytokines, including gamma interferon (IFN-gamma) and interleukin-10 (IL-10) in MNC. The antibody production correlated well with the concentrations of these two cytokines. Addition of recombinant IFN-gamma or IL-10 enhanced antibody production, and monoclonal antibodies to these two cytokines and T-cell depletion significantly reduced antibody production. Intracellular cytokine staining showed that T cells are a major source of IFN-gamma and IL-10. Recombinant Ply and, to a lesser extent, recombinant CbpA induced significant production of IFN-gamma and IL-10 in MNC. T-cell-derived IFN-gamma and IL-10 may be key regulators of production of mucosal antibody to pneumococcal protein antigens in the nasopharynx and may play an important role in local protection against pneumococcal infection in children.

Adenoids↗
PubMed2005

Should healthy children be vaccinated against influenza? A consensus report of the Summits of Independent European Vaccination Experts.

Influenza is often regarded as an illness of the elderly portion of the population because most of the excess mortality associated with influenza epidemics occurs in that age group. However, evidence derived from a large number of clinical studies carried out in different countries and various settings has clearly demonstrated that the burden of influenza is also substantial in children. The attack rates of influenza during annual epidemics are consistently highest in children, and young children are hospitalized for influenza-related illnesses at rates comparable to those for adults with high-risk conditions. Especially among children younger than 3 years of age, influenza frequently predisposes the patient to bacterial complications such as acute otitis media. Children also serve as the main transmitters of influenza in the community. A safe and effective vaccine against influenza has been available for decades, but the vaccine is rarely used even for children with high-risk conditions. Despite several existing problems related to influenza vaccination of children, the current evidence indicates that the advantages of vaccinating young children would clearly outweigh the disadvantages. Considering the total burden of influenza in children, children younger than 3 years of age should be regarded as a high-risk group for influenza, analogously with the age-based definition of high risk among persons 65 years of age or older. Annual influenza vaccination should be recommended to all children from 6 months to 3 years of age.

Age Factors↗
PubMed2005

HIV-1 infection is associated with altered innate pulmonary immunity.

We obtained bronchoalveolar lavage (BAL) fluid from 45 Malawian adults, to measure the concentrations of innate pulmonary immune factors that are important in lung defense against infection. Increased concentrations of the beta -chemokine RANTES were found in BAL fluid from the human immunodeficiency virus (HIV)-1-infected subjects, compared with those in BAL fluid from the HIV-1-uninfected control subjects (mean, 86 pg/mL vs. 0 pg/mL; P<.001). Lysozyme concentrations were also elevated in the HIV-1-infected subjects, compared with those in the HIV-1-uninfected control subjects (1.9 mu g/mL vs. 1.1 mu g/mL; P=.03), but were not elevated in the HIV-1-infected subjects who had recently recovered from invasive pneumococcal disease. Concentrations of lactoferrin and secretory leukocyte protease inhibitor (SLPI) were not different when the subjects were compared by HIV-1 serostatus. Concentrations of RANTES (R2=0.68 and P<.0001) and SLPI (R2=0.29 and P=.001) correlated with BAL fluid HIV-1 load but not with plasma HIV-1 load.

Adult↗
PubMed2005

4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia.

UNLABELLED: Meningococcal disease may present as sepsis, meningitis or a combination of both. Impaired fibrinolysis and massive elevation of the plasminogen activator inhibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis. Previously, an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1gene in a cohort of UK and Dutch children with meningococcal sepsis was reported. We carried out a prospective, multicentre study to investigate the association of the 4G/5G PAI-1 polymorphism, diagnosis, and outcome in meningococcal disease in a Central European and UK population. Blood samples and clinical information of 347 previously healthy children with meningococcal infection were collected from 95 paediatric hospitals in Germany, Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002. Mortality was significantly associated with the 4G/4G genotype (12 of 90 (13%) vs. 15 of 240 (6%), P = 0.037), resulting in an odds ratio of 2.31. The diagnosis of sepsis (independent of symptoms of meningitis) was significantly more frequent in carriers of the 4G/4G genotype (P = 0.01), resulting in an odds ratio of 2.21 to develop sepsis. Meningitis was not associated with the PAI-1 4G/5G polymorphism, and allele frequencies were similar in patient and control groups. CONCLUSION: Our data show a correlation between the 4G/4G genotype in the plasminogen activator inhibitor-1 gene and poor outcome in children with meningococcal infection. In addition, 4G homozygous patients were prone to develop sepsis. We found no influence of the plasminogen activator inhibitor-1 polymorphism on the susceptibility to invasive meningococcal infection.

Adolescent↗
PubMed2005

Pertussis immunization in the global pertussis initiative European region: recommended strategies and implementation considerations.

Approaches to pertussis diagnosis, surveillance and immunization vary widely across Europe. Nonetheless most countries report high levels of vaccine coverage in infants and toddlers, and significant reductions in infant morbidity and mortality have been achieved. As a consequence of the effective protection of infants and toddlers, the absolute incidence of pertussis has substantially decreased, but the relative proportion of older age groups, adolescents and adults in particular, has increased. These groups, however, are a relevant source of infection of unimmunized or incompletely immunized infants. In addition to efficient childhood vaccination, other approaches to pertussis immunization are required. Among the various strategies evaluated, 3 were recommended by the European participants in the Global Pertussis Initiative that might be adapted to each country's specific needs: the reinforcement of implementation of current schedules, the addition of an extra dose of vaccine to current immunization schedules and the selective immunization of health care workers, which is already included in a European Commission directive. The main barriers to the acceptance of these strategies are low awareness of pertussis in immunized populations, poor recognition of the disease in adults and adolescents, lack of standardized diagnostic criteria and poor access to laboratory confirmation of the diagnosis. These obstacles have led to underreporting of pertussis and an underestimation of the disease burden. Actions to overcome these issues are crucial to the implementation of new or improved immunization strategies to combat pertussis in Europe.

Adolescent↗
PubMed2005

Advances in pneumococcal vaccines: advantages for infants and children.

The introduction of Haemophilus influenzae type b (Hib) vaccine into the universal immunisation schedules of many industrialised countries and the subsequent remarkable decline in the incidence of invasive Hib disease has further highlighted the impact of invasive pneumococcal diseases. Streptococcus pneumoniae is now the leading cause of bacterial meningitis in children in many settings and a leading cause of vaccine-preventable bacterial disease in children worldwide. The currently marketed 23-valent pneumococcal polysaccharide vaccine provides large serotype coverage at a relatively low cost. However, it is not efficacious in young children. Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive disease in infants and young children, with favourable safety and immunogenicity profiles. These vaccines have also shown efficacy in reducing cases of non-invasive disease (i.e. otitis media), nasopharyngeal acquisition of vaccine-specific serotypes of S. pneumoniae, and protection against pneumococcal disease caused by resistant strains. However, PCV contains a limited number of pneumococcal serotypes and, given adequate ecological pressure, replacement disease by non-vaccine serotypes remains a threat, particularly in areas with very high disease burden. Furthermore, although capsular-specific antibodies have been shown to be highly protective, it remains unclear what concentration of these serotype-specific antibodies protect against disease and, more recently, it has become clear that opsonic activity and avidity of these antibodies are more critical determinants of protection than concentration. Therefore, monitoring disease burden and defining immune correlates of protection after widespread use of conjugate vaccines are crucial for the evaluation of these new generation vaccines. Furthermore, a need exists to develop pneumococcal vaccines with lower cost and larger serotype coverage. Development of one or more protein vaccines that might be easier and, thus, less expensive to manufacture, and which might provide protection against multiple serotypes, is in progress. This article reviews the current state of pneumococcal disease and pneumococcal vaccines in clinical use.

Child↗
PubMed2004

Bacterial polysaccharide-protein conjugate vaccines.

Following demonstration that chemical conjugation of polysaccharide antigens to proteins could enhance their immunogenicity in the 1920s, interest in this approach to primary prevention of bacterial infections waned with the development and widespread use of antibiotics. Emergence of resistant bacteria rekindled interest in the late 20th century, which saw extremely rapid development and implementation of several vaccines which are already rapidly changing the epidemiology of childhood infections with Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis. Others such as Group B streptococcus and Salmonella typhi infections may soon follow. However, several important questions about the immunology of these antigens remain unanswered and the long-term implications of reducing or eliminating the circulation of organisms which are more commonly nasopharyngeal commensals than pathogenic invaders are uncertain.

Adolescent↗
PubMed2004

Mucosal immune responses to capsular pneumococcal polysaccharides in immunized preschool children and controls with similar nasal pneumococcal colonization rates.

BACKGROUND: Immunization with conjugate pneumococcal vaccines induces significant primary and memory IgG anti-polysaccharide (PS) responses in serum. It can also induce mucosal responses in infants especially after a polysaccharide booster. However, it is unclear whether it can prime for mucosal memory responses on nasal exposure to pneumococcus, which may be important in protection against pneumococcal invasion and/or carriage. METHOD: IgA and IgG to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F (conjugate vaccine serotypes), 1 and 3 (nonvaccine serotypes) capsular PS were measured by immunoassay in saliva from 2- to 5-year-old children previously given three doses of 7-valent pneumococcal conjugate vaccine in infancy, followed by 23-valent PS vaccine at 13 months and from unvaccinated controls of similar age and sex. Salivary antibody responses were analyzed in relation to carriage of pneumococci assessed by bacterial culture of nasopharyngeal swab samples collected in the summer and winter of the year 2000. RESULTS: Rates of detectable IgG antibodies to all vaccine serotypes except 23F were higher in subjects than in controls. No such differences were observed for IgA antibodies except for serotype 6B. Nasal colonization rates were similar, and in both groups mucosal IgA responses were more common and larger than IgG responses. CONCLUSIONS: The mucosal anti-capsular IgA responses observed could develop in response to colonization in preschool children, regardless of vaccination status, and contribute to the falling carriage rates observed with increasing age.

Antibodies, Viral↗
PubMed2003

Immunogenicity of, and immunologic memory to, a reduced primary schedule of meningococcal C-tetanus toxoid conjugate vaccine in infants in the United kingdom.

It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one- or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n = 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10- micro g polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of > or =8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of > or =8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.

Animals↗
PubMed2003

Disparity in functional activity between serum anticapsular antibodies induced in adults by immunization with an investigational group A and C Neisseria meningitidis-diphtheria toxoid conjugate vaccine and by a polysaccharide vaccine.

Polysaccharide-protein conjugate vaccines elicit higher concentrations of serum anticapsular antibody in infants and children than do unconjugated polysaccharide vaccines. The conjugate-induced antibodies also have higher avidity and complement-mediated bactericidal activity. Similar vaccine-related differences in the magnitude or functional activity of antibody are observed infrequently in immunized adults. We compared the antibody responses of adults immunized with an investigational group A and C meningococcal conjugate vaccine to those elicited by an unconjugated meningococcal polysaccharide vaccine. Although there were no significant differences between the respective geometric mean bactericidal titers of the two vaccine groups, it took, on average, three- to fourfold higher concentrations of polysaccharide-induced serum anticapsular antibody to achieve 50% complement-mediated bacteriolysis than conjugate-induced antibody (P < 0.001 for groups A and C). At limiting doses, the polysaccharide-induced anticapsular antibodies also were less effective in conferring passive protection against meningococcal bacteremia in infant rats challenged with a group C strain (P < 0.04). The avidity index of the group C antibodies was higher in the conjugate vaccine group than in the polysaccharide vaccine group (P < 0.005). The disparities in the functional activity of the anticapsular antibodies elicited in adults by the two vaccines imply fundamental differences in the respective B-cell populations stimulated.

Adult↗