Biomedical subjects

H Ahman

Publications and source records attributed to H Ahman.

12 recordsLinked to original sources

PubMed2001

Bridging phase 2 and phase 3 pneumococcal immunologic data for future combination vaccines.

Pneumococcal conjugate vaccines (PncCs) will be introduced into childhood vaccination programs now that the first PncC has been licensed for use. The next generation of PncCs and possible combination vaccines containing PncC will most probably be approved on the basis of phase 2 immunogenicity and safety data. PncCs are combination vaccines that include, at present, 7-11 components. Immune response to different components may vary. Furthermore, there seem to be population-based differences in immune response. Whether these differences are due to the other vaccines that are given simultaneously or due to the genetic background remains to be seen. Immune response can be evaluated by determining both the quantity and the quality of antibodies after vaccination. However, data are still missing on the minimal protective immune response and serologic correlates or surrogates of protection.

Antibodies, Bacterial↗

PubMed2001

Serum and salivary anti-capsular antibodies in infants and children vaccinated with octavalent pneumococcal conjugate vaccines, PncD and PncT.

We studied the immunogenicity of two octavalent pneumococcal (Pnc) conjugate vaccines; Pnc polysaccharides (PS) of serotypes 3, 4, 6B, 9V, 14, 18C, 19F, and 23F were conjugated to diphtheria or tetanus toxoid (PncD and PncT, respectively). Fifty healthy Finnish infants were vaccinated at the ages of 2, 4, 6, and 15 months with either PncD or PncT. Serum IgG antibodies to the vaccine serotypes were analysed by enzyme-linked immunosorbent assay (EIA). All eight PSs induced a significant antibody response both after the primary series and after the booster. Response to PncD was higher for PSs 3, 9V, 14 and 18C and to PncT for serotype 4. Salivary IgA and IgG anti-Pnc antibodies were measured for serotypes 4, 6B, 9V, 14, 18C, and 19F. Mucosal antibodies were found rarely after the primary series but in a greater proportion after the booster. In conclusion, both vaccines were immunogenic.

Antibodies, Bacterial↗

PubMed2001

Serum and salivary anti-capsular antibodies in infants and children immunized with the heptavalent pneumococcal conjugate vaccine.

AIM: To study the ability of seven-valent experimental pneumococcal polysaccharide CRM197 protein conjugate vaccine (PncCRM) to induce antibodies in serum and saliva of infants. METHODS: Sixty Finnish infants received Pnc-CRM vaccine at 2, 4 and 6 months of age and were boosted with PncCRM (n = 30) or pneumococcal polysaccharide (PncPS) (n = 29) vaccine at the age of 15 months. Serum IgG antibody concentrations to vaccine serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were measured by enzyme immunoassay at 2, 4, 6, 7, 15, 16 and 24 months of age. Salivary IgA, IgG and secretory Ig antibody titers at 7 and 16 months of ages were analyzed by enzyme immunoassay against the same serotypes, except 23F. RESULTS: PncCRM induced systemic immune responses and immunologic memory. At 7 months of age 69 to 100% of children, depending on the serotype, had serum IgG antibody concentrations exceeding the value of 1.0 microg/ml. At 15 months the titers were still higher than before the vaccinations. Booster doses of either PncPS or PncCRM induced an increase in antibody concentrations. The titers were still elevated at 24 months of age. Salivary IgA and IgG antibodies were found rarely at 7 months of age, but in up to 80% of samples taken at 16 months of age, depending on the serotype and nature of the booster vaccine. Salivary IgG correlated with IgG in serum, supporting the theory that salivary IgG is derived from serum. Salivary IgA and secretory Ig correlated positively, which indicates that IgA was locally produced. CONCLUSIONS: PncCRM induces both systemic and mucosal immune responses in infants.

Antibodies, Bacterial↗

PubMed2001

Tolerability and immunogenicity of an eleven-valent pneumococcal conjugate vaccine in healthy toddlers.

BACKGROUND: A need to increase the serotype coverage of pneumococcal conjugate vaccines exists. The use of a single carrier protein may cause overload of the carrier and decrease the immune response by not providing sufficient carrier-specific T helper cell support. A vaccine composed of a mixture of tetanus- and diphtheria-conjugated polysaccharides (PS) is a potential solution to this issue. OBJECTIVES: The aim of this study was to assess the tolerability and immunogenicity in healthy toddlers of an 11-valent pneumococcal conjugate vaccine that uses both tetanus and diphtheria toxoids as carriers. We explored the effect of an aluminum adjuvant on safety and immunogenicity by comparing the vaccine with and without adjuvant. METHODS: Twenty Finnish and 23 Israeli toddlers received the conjugate vaccine with or without aluminum adjuvant. Safety data were recorded for 5 days after vaccination. Sera were obtained before and 28 days after the immunization. IgG antibodies to the 11 vaccine-type PSs were determined by enzyme immunoassay. RESULTS: No serious adverse events occurred. The formulation with the adjuvant tended to induce fewer local but more systemic reactions than the non-adjuvant-containing formulation. Both vaccine formulations induced significant IgG increases for the vaccine-specific PSs. Types 3 and 7F were the most immunogenic; antibodies reached a concentration of 1 microg/ml in all individuals. Conjugates of types 6B, 14 and 23F were the weakest immunogens; antibodies reached the concentration of 1 microg/ml in 36, 27 and 32% of the individuals in the nonadjuvant group and in 53, 38 and 53% in the adjuvant group, respectively. CONCLUSIONS: An 11-valent mixed carrier pneumococcal conjugate vaccine is safe and immunogenic in toddlers. The use of an adjuvant do not seem to offer any significant benefit.

Adjuvants, Immunologic↗

PubMed2000

Salivary anti-capsular antibodies in infants and children immunised with Streptococcus pneumoniae capsular polysaccharides conjugated to diphtheria or tetanus toxoid.

Saliva samples of infants and children immunised with pneumococcal vaccines were analysed for anti-polysaccharide (PS) antibodies against the Streptococcus pneumoniae (Pnc) vaccine serotypes 6B, 14, 19F, and 23F. The children received Pnc conjugate vaccine (1, 3, or 10 micrograms of PSs conjugated to diphtheria or tetanus toxoid) or placebo at 2, 4, and 6 months. At 7 months of age salivary PS antibodies were detected rarely. All children received Pnc conjugate or PS vaccine at 14 months of age. At 15 months, both IgA and IgG anti-Pnc PS were found, anti-19F and anti-14 antibodies occurring most frequently and in the highest concentrations. IgA was in the secretory form and predominantly IgA1. A negative dose dependency was observed in IgA anti-19F response. In general, no clear differences in salivary antibody responses were found between the children primed with conjugate vaccine in infancy and those who received their first Pnc vaccine at 14 months of age, suggesting that priming with Pnc conjugate vaccines does not lead to remarkable mucosal memory responses.

Antibodies, Bacterial↗

PubMed1999

Dose dependency of antibody response in infants and children to pneumococcal polysaccharides conjugated to tetanus toxoid.

Three injections of tetravalent pneumococcal polysaccharide-tetanus toxoid conjugate vaccine (PncT) were given to infants at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and Haemophilus influenzae type b-tetanus toxoid conjugate vaccines. Three doses (1, 3 or 10 microg) of polysaccharides were used. Children were boosted with unconjugated polysaccharide vaccine at 14 months of age. No dose dependency was seen after primary immunization. However, booster response to three vaccine serotypes was highest in the group primed with the lowest dose of conjugate vaccine. As the magnitude of the response to booster may be related to the number of polysaccharide-specific memory B cells, we hypothesize that the 10 microg dose of the tetravalent conjugate vaccine is too high for optimal induction of immunologic memory.

Antibodies, Bacterial↗

PubMed1999

Differences in the avidity of antibodies evoked by four different pneumococcal conjugate vaccines in early childhood.

Avidity of antibodies to Streptococcus pneumoniae type 6B, 14, 19F and 23F polysaccharides (PS) evoked by four different pneumococcal conjugate vaccines was compared. Infants were primed with pneumococcal PS conjugated to the variant diphtheria toxin CRM197 (PncCRM), diphtheria toxoid (PncD), tetanus toxoid (PncT) or meningococcal protein complex (PncOMPC) and boosted with the homologous conjugate or PS vaccine. No booster was given to children in the PncOMPC group. Relative antibody avidity was measured by thiocyanate EIA. No vaccine specific differences were found in avidity of anti-14 or -19F antibodies. By contrast, antibody avidity to 6B and 23F differed significantly between the vaccine groups, PncCRM and PncT inducing antibodies of highest avidity.

Age Factors↗

PubMed1998

Avidity of IgG for Streptococcus pneumoniae type 6B and 23F polysaccharides in infants primed with pneumococcal conjugates and boosted with polysaccharide or conjugate vaccines.

Relative avidity of IgG to Streptococcus pneumoniae type 6B and 23F polysaccharides (PSs) was measured in sera of children immunized with pneumococcal vaccines, using an EIA and the chaotropic agent thiocyanate. Infants were immunized at 2, 4, and 6 months of age with pneumococcal PS-diphtheria toxoid conjugate vaccine, and boosted at 14 months with the homologous conjugate or a pneumococcal PS vaccine. The concentrations of antibodies to 6B and 23F PSs increased significantly after the booster with both vaccines. A significant increase in the avidity of anti-6B and anti-23F antibodies was seen after the booster with conjugate but not with PS vaccine. Avidity also increased in another group of infants primed and boosted with pneumococcal PS-meningococcal protein conjugate but not in a group boosted with PS vaccine after priming with pneumococcal PS-tetanus toxoid conjugate. In the latter group, however, the avidity of anti-6B was high before boosting.

Antibodies, Bacterial↗

PubMed1998

Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid conjugate vaccine is immunogenic in early infancy and able to induce immunologic memory.

BACKGROUND: Pneumococcal polysaccharide vaccines are not protective against the most common pneumococcal infections in infancy. The importance of pneumococcal diseases and emerging antimicrobial resistance emphasize the need for prophylaxis. METHODS: Pneumococcal conjugate vaccine, containing capsular polysaccharides from serotypes 6B, 14, 19F and 23F conjugated to diphtheria toxoid (PncD), was given to 75 infants at 2, 4 and 6 months of age. Three dosages (1, 3 or 10 microg of each) were used. A placebo group of 49 infants received physiologic saline. Children were given a booster dose of either polysaccharide or conjugate vaccine at 14 months of age; the placebo group received conjugate vaccine. Antibody concentrations were determined with an enzyme immunoassay. RESULTS: The highest dose induced the strongest response after primary immunization, but booster response was greatest in the group primed with the lowest dose. Polysaccharide and conjugate vaccines induced booster responses of the same magnitude. At 24 and 36 months of age the antibody concentrations were similar in children who had received the PncD in infancy and in children immunized at 14 months of age only. CONCLUSIONS: The PncD conjugate vaccine is immunogenic and able to induce immunologic memory.

Antibodies, Bacterial↗

PubMed1996

Pentavalent pneumococcal oligosaccharide conjugate vaccine PncCRM is well-tolerated and able to induce an antibody response in infants.

BACKGROUND: The emergence of resistant pneumococci makes the treatment of pneumococcal diseases difficult. The currently available polysaccharide vaccines have very limited efficacy in young children. The immunogenicity can be improved by covalent coupling to protein carriers as has been shown with Haemophilus influenzae type b. METHODS: Thirty healthy infants were immunized with a pneumococcal conjugate vaccine at 2, 4 and 6 months of age. Oligosaccharides were derived from capsular polysaccharides of types 6B, 14, 18C, 19F and 23F and conjugated to the nontoxic mutant diphtheria toxin CRM197. The final vaccine was a mixture of these conjugates, containing 10 micrograms of each oligosaccharide. The infants received simultaneously H. influenzae type b oligosaccharide-CRM197 conjugate vaccine. Serum samples were taken before each dose and 1 month after the third dose. Control material was composed of 25 serum samples taken from children of the same age without pneumococcal vaccination. Enzyme-linked immunosorbent assay was used to measure serum IgG anti-pneumococcal polysaccharide concentrations and radioimmunoassay for the serum Ig anti-H. influenzae type b concentrations. RESULTS: PncCRM vaccine was well-tolerated. Pneumococcal type 18C induced a significant antibody increase after the first dose, whereas the other five oligosaccharides, including H. influenzae type b oligosaccharides, induced an increase after the second or third dose. The specific IgG concentrations at 7 months of age were significantly higher among the vaccinated infants than in the controls for all the five pneumococcal types. CONCLUSIONS: Pneumococcal oligosaccharide-CRM197 conjugate vaccine is able to induce an IgG serum response in infants and anti-pneumococcal antibody concentrations were significantly higher than in controls of same age.

Antibodies, Bacterial↗

PubMed1995

Pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine is immunogenic in infants and children.

Sixty-two infants and 31 toddlers were vaccinated with the tetravalent pneumococcal conjugate vaccine PncOMPC consisting of the capsular polysaccharide of pneumococcal types 6B, 14, 19F, and 23F conjugated to the outer membrane protein complex of Neisseria meningitidis. Infants were vaccinated at 2, 4, and 6 months (group A) or at 4, 6, and 14 months (group B); toddlers were vaccinated at 24 or at 24 and 26 months of age. The IgG responses to the four pneumococcal polysaccharide types were measured by EIA. In infants, types 14 and 19F induced a significant response after the first dose and types 6B and 23F after the second dose. A clearcut booster response was seen to the booster dose given at 14 months, indicating immunologic priming by the primary series at 2-6 months of age. The responses of the toddlers to one or two doses of the vaccine were very similar to the responses in infants.

Antibodies, Bacterial↗

PubMed1994

Ribotyping as an epidemiologic tool for Escherichia coli.

Restriction fragment length polymorphism of ribosomal RNA genes was analysed among 133 Escherichia coli strains predominantly from blood and urine, including 21 isolates from faeces of healthy persons. The strains had also been characterized for their O:K:H serotypes, for the presence of P, S and type 1C fimbriae, non-P, non-S mannose-resistant haemagglutinins and haemolysin production. Hind III-digested genomic DNA was subjected to Southern blot analysis with either plasmid pKK3535 containing E. coli rRNA operon or purified rRNA as a probe. Among the 133 strains 20 ribotypes were obtained. The distribution of strains into different ribotypes generally correlated with their O:K:H serotype. Ribotype variation within serotypes was mainly seen among strains with the K5 capsule. The origin of the strains or the presence of virulence-associated factors did not correlate with the ribotype. In conclusion, ribotyping appears to be a valuable method in epidemiologic studies especially when the serotyping methods are not available.

Bacterial Adhesion↗