Biomedical subjects

J Eskola

Publications and source records attributed to J Eskola.

At least 19 recordsLinked to original sources

PubMed2006

A TL-based anthropomorphic benchmark for verifying 3-D dose distributions from external electron beams calculated by radiotherapy treatment planning systems.

Initial results are reported of a Polish-Finnish project to verify electron dose distributions calculated by treatment planning systems (TPSs), CadPlan v.6.3.2 and Theraplan v.3.5, which use different electron beam dose distribution algorithms. Treatment of gross tumour volumes representing lung and parotid cancer was simulated in an Alderson anthropomorphic phantom with thermoluminescent detectors (TLDs) (Li(2)B(4)O(7):Mn,Si) placed at selected measurement points inside its volume. The observed discrepancy between relative values of dose calculated and measured by TLDs at each of the measurement points and those calculated by the different TPSs at the same points is discussed.

Algorithms↗

PubMed2001

Booster response to the tetanus and diphtheria toxoid carriers of 11-valent pneumococcal conjugate vaccine in adults and toddlers.

We measured the tetanus and diphtheria antitoxin responses after administration of one dose of a mixed carrier (tetanus and diphtheria toxoids) 11-valent pneumococcal conjugate vaccine (PncDT) in 20 Finnish adults (mean age 26.1 years) and 20 Finnish (mean age 23.2 months) and 23 Israeli (mean age 18.5 months) toddlers. The vaccinees had previously been immunised with multiple doses of vaccines containing diphtheria and tetanus toxoids. A double-antigen ELISA was used to measure the antitoxin concentrations. PncDT induced significant booster responses in both adults and toddlers to the tetanus and the diphtheria carrier proteins. Thus, the effect on the tetanus and diphtheria immunity of multivalent conjugate vaccines containing tetanus and diphtheria toxoids as carriers needs to be evaluated before such vaccines are routinely implemented.

Adult↗

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

Avidity and subclasses of IgG after immunization of infants with an 11-valent pneumococcal conjugate vaccine with or without aluminum adjuvant.

Finnish and Israeli infants received an 11-valent mixed-carrier pneumococcal conjugate vaccine with or without aluminum adjuvant at 2, 4, 6, and 12 months of age. The relative avidity of serotype 1-, 5-, 6B-, 14-, 19F-, and 23F-specific IgG antibodies in serum obtained at 7, 12, and 13 months of age was measured by EIA, using thiocyanate as a chaotropic agent. For all serotypes, except 14, avidity increased between the ages of 7 and 12 months. After boosting at 12 months, avidity further increased for all serotypes. The adjuvant improved antibody avidity against serotype 5. The IgG antibodies produced were mainly IgG1 subclass, although some infants also produced IgG2 after boosting. In conclusion, the immunization of infants with this 11-valent pneumococcal conjugate vaccine increased avidity of IgG, suggesting successful immunologic priming.

Adjuvants, Immunologic↗

PubMed2001

Cross-reactivity of antibodies to type 6B and 6A polysaccharides of Streptococcus pneumoniae, evoked by pneumococcal conjugate vaccines, in infants.

Streptococcus pneumoniae serotypes 6B and 6A are important causes of infections, yet only 6B is included in current vaccines. It is, therefore, crucial to evaluate whether functional antibodies are produced against both types after vaccination. Concentration and opsonophagocytic activity (OPA) of antibodies to 6B and 6A polysaccharides were determined in serum samples from infants immunized with 3 different pneumococcal conjugate vaccines containing serotype 6B. In all vaccine groups, a significant correlation was found between the anti-6B and -6A antibody concentration and OPA. However, OPA to the vaccine serotype was detectable more commonly than OPA to the cross-reactive type. Furthermore, 5%-15% of the serum samples showed high OPA against the 6B but not the 6A strain. On average, 2-6 times more anti-6B antibodies were needed for 50% opsonophagocytic killing of the type 6A than the type 6B strain. Although pneumococcal type 6B conjugate vaccines elicit antibodies that cross-react with type 6A, not all anti-6B antibodies are functionally cross-reactive.

Antibodies, Bacterial↗

PubMed2001

Tolerability and immunogenicity of an 11-valent pneumococcal conjugate vaccine in adults.

We studied the safety and immunogenicity in healthy adults of an 11-valent pneumococcal conjugate vaccine. Capsular polysaccharides (PS) of serotypes 1, 4, 5, 7F, 9V, 19F and 23F were conjugated to tetanus toxoid, and of serotypes 3, 6B, 14 and 18C to diphtheria toxoid. Ten subjects received the conjugate vaccine with and the other ten subjects without aluminium hydroxide adjuvant. The reference vaccine was a marketed 23-valent PS vaccine. Safety data were recorded over 5 days after the immunisation. IgG antibody concentrations, avidity and subclass distribution were measured by EIA. The conjugate without aluminium induced more local adverse effects than the conjugate with aluminium or PS vaccine. All vaccines evoked significant antibody increases to all vaccine specific antigens. Both conjugate vaccines induced antibodies mainly of IgG(2) subclass, and adjuvanted conjugate vaccine induced IgG antibodies with increased avidity. This first administration, to man, of a mixed protein carrier 11-valent pneumococcal conjugate vaccine demonstrated its ability to induce an immune response without significant adverse effects, enabling further study on its use in paediatric populations.

Adjuvants, Immunologic↗

PubMed2001

Efficacy of a pneumococcal conjugate vaccine against acute otitis media.

BACKGROUND: Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae. METHODS: We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy. RESULTS: Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent. CONCLUSIONS: The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.

Acute Disease↗

PubMed2001

Age- and dose-interval-dependent antibody responses to inactivated poliovirus vaccine.

Antibody responses were studied in five groups of children immunized with different three-dose schedules of inactivated poliovirus vaccine (IPV). The age of the child at the first dose (1-4 months) and the interval between the first and second doses (2-4 months) influenced the initial responses in a serotype-dependent manner. All the groups attained sufficient antibody level after three doses but the third dose given at 18 months resulted in higher persisting antibody levels than that given at 12 months. The highest persisting antibody titers against PV1 and PV2 (but not against PV3) at the age of 3 years were measured in the control group immunized with the current schedule (P < 0.001) in which the first dose is given at 6 months. The level of maternal antibodies present at the time of the first dose correlated negatively with the antibody titers as late as at 3 years of age. It is concluded that three doses of IPV given in widely variable schedules may result in satisfactory immune responses in children but, for optimal results, very early onset of the program and short dosage intervals should be avoided.

Age Factors↗

PubMed2001

Tetravalent meningococcal polysaccharide vaccine is immunogenic in adult allogeneic BMT recipients.

Forty-four adult BMT recipients transplanted from an HLA-identical sibling donor were randomized to receive meningococcal polysaccharide (Men PS) vaccine either 8 (early group; 22 patients) or 20 (late group; 22 patients) months after BMT. The geometric mean concentrations (GMC) of antibodies to serogroup A Neisseria meningitidis (Men A) and serogroup C Neisseria meningitidis (Men C), determined by an EIA method, decreased during the first 6 months after BMT but remained at a stable level thereafter. Before vaccination the GMCs of anti-Men A were 1.53 microg/ml and 1.61 microg/ml, but 1 month after vaccination they were significantly higher, 3.46 microg/ml and 6.39 microg/ml, in the early and late groups. The GMCs of anti-Men C increased from 0.37 microg/ml and 0.44 microg/ml before vaccination to 3.31 microg/ml and 4.62 microg/ml at 1 month after vaccination in the early and late groups, respectively. By 6 months after vaccination the GMCs of Men antibodies had decreased to levels of about 50% of those measured at 1 month after vaccination. Two-fold responses to Men A PS were seen in 52% and 74% and to Men C PS in 76% and 89% of the BMT recipients in the early and late groups, respectively. Chronic GVHD had no influence on the vaccination response. In the present study, Men PS vaccine induced good and equal antibody responses to Men A and Men C PSs in allogeneic BMT recipients regardless of timing after BMT. Vaccination against Neisseria meningitidis should be considered, especially in the event of travelling or military service > or = 8 months after BMT.

Adolescent↗

PubMed2001

Activation of cell-mediated immunity following immunization with pneumococcal conjugate or polysaccharide vaccine.

The immunogenicity of pneumococcal polysaccharide (PS) vaccines can be improved by conjugating PS to a polypeptide carrier that alters the immune response from T-cell independent to T-cell dependent. In order to study the influence of PS or protein antigens as inducers of cell-mediated responses, 30 adults were immunized with a 23-valent pneumococcal PS vaccine (PS-group) or an 11-valent, tetanus and diphtheria mixed carrier conjugate vaccine with (adjuvant group) or without aluminium adjuvant (nonadjuvant group). Cell-mediated responses were analyzed on days 0, 14 and 28 after vaccination by measuring lymphocyte proliferation and production of interferon (IFN)-gamma (Th1 marker) or interleukin (IL)-4 and IL-5 (Th2 markers) cytokines after in vitro stimulation with the PS and protein components of the vaccines. Tetanus and diphtheria proteins were the main inducers of lymphocyte proliferative and cytokine responses. Conjugate vaccines induced increased proliferative responses to the tetanus or diphtheria protein, but not to the PS components. In the PS-group, a lymphocyte proliferative response to protein antigens was not observed. The number of antigen-specific and nonspecific IFN-gamma-secreting cells detected by ELISPOT tended to increase in all three groups in response to protein or to PS antigen. No major differences were detected in the number of IL-4-secreting cells measured 14 and 28 days after vaccination. The conjugate vaccine with adjuvant was associated with Th2 type of activation indicated by an enhanced IL-5 secretion in response to the tetanus and diphtheria protein antigens.

Adjuvants, Immunologic↗

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

Polysaccharide-based pneumococcal vaccines in the prevention of acute otitis media.

New pneumococcal vaccines, consisting of 7-11 capsular polysaccharides coupled to protein carriers, are able to induce functionally active humoral and mucosal antibody responses. They also reduce mucosal carriage of pneumococci in the vaccinees. Preliminary results from efficacy trials suggest that about one-third of pneumococcal otitis could be prevented by using the seven-valent pneumococcal conjugate vaccine. If these efficacy estimates are true throughout childhood, up to 1.2 million episodes of acute otitis are preventable annually in the US. The true impact of the vaccine on otitis burden is dependent not only on the efficacy as demonstrated in the efficacy trials but also on the impact of the vaccine on the mucosal carriage of bacteria and on the herd immunity induced by vaccinations. Ongoing follow-up studies will reveal whether these factors increase or decrease the efficiency of the proposed vaccination programme.

Acute Disease↗

PubMed2000

Influence of codon usage on the immunogenicity of a DNA vaccine against tetanus.

Two related DNA vaccine vector plasmids, harbouring either wild-type (pcDNA3/ntetC) or synthetic codon optimised (pcDNA3/stetC) DNA encoding fragment C (TetC) of tetanus toxin were constructed. COS-7 cells transformed with pcDNA3/stetC reproducibly expressed higher levels of TetC than similar cells transformed with pcDNA3/ntetC. BALB/c mice immunised intramuscularly with pcDNA3/stetC produced significantly higher levels of anti-TetC antibodies in their serum in the weeks following vaccination compared to mice immunised with pcDNA3/ntetC, even when differences in the CpG content between the two sequences were controlled for using non-expressing DNA.

Animals↗

PubMed2000

Human immune response to streptococcal inhibitor of complement, a serotype M1 group A Streptococcus extracellular protein involved in epidemics.

Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made by serotype M1 group A Streptococcus strains that contributes to bacterial persistence in the mammalian upper respiratory tract. New variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic was analyzed. Of 636 persons living in diverse localities, 43% had anti-Sic serum antibodies, but only 16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in nasal wash specimens in high frequency. Linear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hypervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. These results support the hypothesis that selection of Sic variants occurs on mucosal surfaces by a mechanism that involves acquired host antibody.

Adolescent↗

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↗

PubMed2000

Etiology of community-acquired pneumonia in 254 hospitalized children.

BACKGROUND: Childhood community-acquired pneumonia is a common illness, but there have been relatively few comprehensive studies of the viral and bacterial etiology in developed countries. The aim of the present investigation was to determine the etiology of community-acquired pneumonia in hospitalized children by several laboratory methods. METHODS: In a 3-year prospective study a nasopharyngeal aspirate for viral studies and acute and convalescent serum samples for viral and bacterial serology were taken from 254 children with symptoms of acute infection and infiltrates compatible with pneumonia in the chest radiograph. The role of 17 microbes was investigated. RESULTS: A potential causative agent was detected in 215 (85%) of the 254 patients. Sixty-two percent of the patients had viral infection, 53% had bacterial infection and 30% had evidence of concomitant viral-bacterial infection. Streptococcus pneumoniae (37%), respiratory syncytial virus (29%) and rhinovirus (24%) were the most common agents associated with community-acquired pneumonia. Only one patient had a positive blood culture (S. pneumoniae) of 125 cultured. A dual viral infection was detected in 35 patients, and a dual bacterial infection was detected in 19 patients. CONCLUSIONS: The possible causative agent of childhood community-acquired pneumonia can be detected in most cases. Further studies are warranted to determine what etiologic investigations would aid in the management of pneumonia. With effective immunization for S. pneumoniae and respiratory syncytial virus infections, more than one-half of the pneumonia cases in this study could have been prevented.

Age Distribution↗

PubMed2000

Immunogenicity of pneumococcal conjugate vaccines.

BACKGROUND: Prevention of pneumococcal infections is a public health priority because of the high impact of the disease and because of the increasing problems due to antimicrobial resistance. Traditional vaccines, consisting of purified capsular polysaccharides (PSs) of Streptococcus pneumoniae, are not immunogenic in young children. In addition they confer only limited protection in patients with immunodeficiencies and hematologic malignancies. IMMUNOGENICITY OF PNEUMOCOCCAL CONJUGATE VACCINES: Immunogenicity of the PS vaccine has been enhanced by coupling pneumococcal PSs to proteins to produce a conjugate vaccine. Conjugate molecules are designed to possess T cell dependent properties, such as immunogenicity in early infancy, stimulation of high levels of IgG isotype antibodies and enhanced immunologic memory responses. In the clinical studies multivalent pneumococcal conjugate vaccines have been shown to induce an IgG-dominating serum antibody response against common pneumococcal serotypes causing infections in children. A booster dose later in life creates a robust and rapid antibody response, indicating the existence of immunologic memory in primed children. Antibodies induced by conjugate vaccines are functionally active, as demonstrated by their high avidity and opsonophagocytic activity.

Bacterial Vaccines↗