Inharmonious coexistence.
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Communicable Disease Control↗
Biomedical subjects
Adam Finn
Publications and source records attributed to Adam Finn.
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↗
The role of chemokines in sepsis and septic shock.
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Animals↗
Prior meningococcal A/C polysaccharide vaccine does not reduce immune responses to conjugate vaccine in young adults.
The immune responses induced in young adults by a meningococcal A/C polysaccharide-diphtheria toxoid conjugate vaccine (Mcj) and a meningococcal A/C plain polysaccharide vaccine (Mps) were evaluated in unvaccinated subjects and those who had received either vaccine previously. 195 subjects aged 17-30 years received either Mps or Mcj. After 12 months, they were randomised again to receive a second dose of either vaccine. Serogroup specific serum bactericidal assay (SBA) titers and IgG antibody responses were assayed before and 4-8 weeks after primary and booster immunisation. Both vaccines were immunogenic in previously unvaccinated subjects. Administration of a dose of Mps after previous Mps or Mcj induced lower bactericidal titers to group C Neisseria meningitidis than those seen after a single dose of Mps. Bactericidal antibody responses to Mcj were not reduced in subjects who had previously received Mps.
Adolescent↗
Induction of functional secretory IgA responses in breast milk, by pneumococcal capsular polysaccharides.
Capsule-specific secretory IgA (s-IgA) in breast milk may enhance protection against pneumococcal disease in infants. After immunization of 3 lactating mothers with 23-valent polysaccharide vaccine, specific s-IgA, but not IgG, increased by >2-fold in milk of at least 1 subject for 6 of 7 serotypes. The s-IgA was predominantly IgA1, in secretory form, and highly specific with avidity distinct from serum IgA and IgG. Milk whey from 2 immunized women supported dose- and complement-dependent killing of Streptococcus pneumoniae serotypes 19F and 14 by human neutrophils, as did purified s-IgA to serotype 19F. These data reveal that capsule-specific human s-IgA in breast milk can initiate killing of S. pneumoniae, providing proof of concept that vaccine-induced human mucosal s-IgA can support functional bactericidal activity. Determining the biologic role for s-IgA in killing and inhibiting adherence of S. pneumoniae in vivo will contribute to the development of mucosal vaccines against S. pneumoniae.
Bacterial Adhesion↗
Choline-binding protein A of Streptococcus pneumoniae elicits chemokine production and expression of intercellular adhesion molecule 1 (CD54) by human alveolar epithelial cells.
Recruitment of neutrophils into alveolar air spaces is an early event in the pathogenesis of pneumonia due to Streptococcus pneumoniae. This results from chemokines released by activated endothelial and epithelial cells and alveolar macrophages. Culture supernatants of 6 wild-type strains of S. pneumoniae, shown to contain choline-binding protein A (CbpA; clades A and B), induced release of chemokine CXCL8 from the human alveolar epithelial cell line A549, whereas a CbpA deletion mutant elicited significantly reduced CXCL8 release, compared with that of its isogenic parent (P<.01). Recombinant CbpA up-regulated expression of messenger RNA of CXCL8 and CCL2 but not of XCL1, CXCL10, CCL1, CCL3, CCL4, or CCL5 in A549 cells and induced increased secretion of CXCL8, CCL2, CXCL1, and CXCL5 in a dose- and time-dependent manner. CbpA also increased the expression of intercellular adhesion molecule 1 (CD54) by A549 cells. Thus, CbpA of S. pneumoniae induces the transcription and release of proinflammatory molecules by human alveolar epithelial cells.
Antigens, Bacterial↗
MMR vaccine debate. Competing interests need to be declared.
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Conflict of Interest↗
Estimating the potential health gain and cost consequences of introducing a pre-school DTPa pertussis booster into the UK child vaccination schedule.
This work estimates the health and cost impacts of a pre-school booster vaccination for Bordetella pertussis, when added to existing UK primary vaccination. A transition state simulation model of pertussis infection in a closed population was constructed comprising of susceptible, infected and immune population sub-groups, across eight age bands. Epidemiological, service use and cost data were sourced from routine statistics, published literature and clinician estimates. The introduction of a pre-school booster is predicted to reduce the number of hospitalisations by approximately 1400 and pertussis cases suffered by up to 28,000 at a net investment of under 13 million pounds over a 5-year period.
Child, Preschool↗
Mucosal immune responses to meningococcal conjugate polysaccharide vaccines in infants.
BACKGROUND: Serogroup C meningococcal conjugate polysaccharide vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants. Because meningococcus is a mucosal pathogen colonizing the nasopharynx, local mucosal immune responses may play an important role in host defense against infection and carriage. We have investigated the mucosal IgA and IgG antibody responses to two meningococcal C conjugate vaccines in the saliva of healthy infants. METHODS: Specific salivary IgA and IgG antibodies to two meningococcal C polysaccharide conjugate vaccines (Menjugate from Chiron Corp., n = 46; and Meningitec from Wyeth Lederle, n = 54) were investigated by immunoassay in infants after parenteral vaccinations at the ages of 2, 3 and 4 months. Unstimulated saliva samples were collected immediately before the first immunization and 1 month after the third immunizations. Forty healthy infants receiving the same routine vaccines but no meningococcal C vaccine were recruited as controls. RESULTS: There were significant increases in meningococcal C polysaccharide-specific IgG antibody concentrations postvaccination compared with prevaccination concentrations in both vaccinated groups (both P < 0.001), but no change in the control group. There were no significant increases in specific IgA postvaccination geometric mean concentrations in either the vaccine or the control groups. The number of IgA positives postvaccination increased slightly in the Wyeth vaccine group vs. controls (P < 0.05). CONCLUSIONS: Significant salivary IgG antibodies to meningococcal C polysaccharide were observed after parenteral immunization with two meningococcal C conjugate vaccines, whereas there was no significant increase in specific IgA antibody levels for these two vaccines.
Antibodies, Bacterial↗
Immune responses to novel pneumococcal proteins pneumolysin, PspA, PsaA, and CbpA in adenoidal B cells from children.
Studies of mice suggest that pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, are promising vaccine candidates. To determine whether these proteins are good mucosal immunogens in humans, adenoidal lymphocytes from 20 children who had adenoidectomies were isolated and tested by ELISpot for antigen-specific antibody-secreting cells (ASCs). Cells were also cultured for 7 days in the presence of a concentrated culture supernatant (CCS) from a type 14 strain of pneumococcus which contained secreted pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, and then tested by ELISpot. ELISpot assays done on freshly isolated cells detected ASCs to all four antigens in most children studied. However, there were differences both between antigens and between isotypes. The densities of immunoglobulin G (IgG) ASCs against both PsaA and CbpA were significantly higher than those of ASCs for PspA and PdB (pneumolysin toxoid B) (P < 0.001). For all antigens, the numbers of IgA ASCs tended to be lower than those of both IgG and IgM ASCs. The numbers of anti-CbpA and -PsaA IgA ASCs were higher than those of anti-PdB IgA ASCs (P < 0.01). Concentrations of IgA antibodies to PspA and PsaA in saliva correlated with the numbers of IgA ASCs to PspA and PsaA in freshly isolated adenoidal cells, but no such correlation was found between salivary IgG antibody concentrations and IgG ASCs to the four antigens in adenoidal cells. In cultured cells, anti-PspA, -PsaA, and -CbpA IgG ASCs proliferated significantly, but only two of eight samples showed >2-fold increases in anti-CbpA and -PspA IgA ASCs after CCS stimulation. The results suggest that CbpA, PsaA, and PspA may be good upper respiratory mucosal antigens in children. Adenoids may be important inductive sites for memory IgG responses and important sources of salivary IgA. Some protein antigens may also prime for mucosal IgA memory. These data support the effort to explore mucosal immunization against pneumococcal infection.
Adenoids↗
Meningococcal serogroup C conjugate vaccine.
Meningococcal meningitis and septicaemia are important causes of morbidity and mortality in many parts of the world. More than 90% of the cases are caused by serogroups A, B and C; the remaining 10% are largely caused by the W-135 and Y strains. During the mid-to-late 1990s there was an increase in meningococcal serogroup (MS) C disease in the UK and some parts of Europe. MS C polysaccharide vaccines that were developed in the 1960s are weakly immunogenic and not protective in infants under 2 years of age, but are effective in older recipients. Meningitec (Wyeth-Ayerst) is produced by conjugation of serogroup C oligosaccharide with a mutant diphtheria protein (CRM197), with the aim of inducing T-cell dependent immune responses. It has been found to be immunogenic in infants, toddlers, older children and adults. The vaccine has also been shown to induce immunological memory and therefore is likely to give long-term protection against disease. It received a license for use in the UK in October 1999 and was introduced into the UK immunisation schedule in November 1999. Surveillance studies after introduction of this and similar vaccines have demonstrated a dramatic fall in the incidence of MS C disease. Pre-licensure research studies and post-licensure adverse event data have confirmed that the vaccine is safe.
Adult↗