Mean Antibody Concentrations Research Articles

Immunogenicity and Safety of a Pediatric Dose of a Virosome-Adjuvanted Hepatitis A Vaccine

The availability of pediatric formulations of hepatitis A virus (HAV) vaccines would facilitate the introduction of universal mass vaccination against HAV. The objective of this study was to compare a pediatric dose (0.25 mL) of Epaxal, a virosomal, aluminum-free HAV vaccine, to 0.5 mL standard dose, and to alum-adsorbed HAV vaccine. Subjects aged 1-16 years, stratified for age, were randomized (2:2:1) into group A (0.25 mL Epaxal), group B (0.5 mL Epaxal), or group C (Havrix Junior). Vaccines were administered at months 0, 6. Seroprotection rates (>or=10 mIU/mL anti-HAV antibodies) were assessed for noninferiority, defined as lower limit of 1-sided 97.5% CI >-10%. Incidence of local solicited adverse events and unsolicited adverse events were recorded. Mean age of 308 enrolled subjects was 8.9 years (range, 1.0-17.0 years). All 3 vaccines were highly immunogenic. Noninferiority of group A versus group B and group C with regard to seroprotection was demonstrated after both vaccine doses for the entire study group and for all age subgroups (11-23 months, 2-4, 5-7, 8-10, 11-13, 14-16 years). One month after first vaccination, geometric mean antibody concentrations were 69.0, 83.5, and 50.5 mIU/mL for the 3 groups, respectively (A versus B, P = 0.0208; A versus C, P = 0.0015). Local injection site pain occurred more frequently in group C than in groups A and B. No subjects withdrew from study or reported any vaccine-related serious adverse event. In children aged 1-16 years, 0.25 mL dose of Epaxal is as immunogenic as standard 0.5 mL dose and Havrix Junior. The aluminum-free vaccine compares favorably to comparator vaccine regarding local reactogenicity.

Seroprevalence of antibodies to poliovirus in individuals living in Portugal, 2002

The last case of poliomyelitis in Portugal caused by indigenous wild poliovirus occurred in 1986 and the country was declared polio-free in 2002. High levels of immunity must be maintained to prevent the importation of wild poliovirus. In this study, we determined the immunity against poliomyelitis of the Portuguese population in order to identify possible immunity gaps. A representative sample of 1,133 individuals older than two years residing in mainland Portugal was studied. Logistical difficulties regarding quick sample transportation precluded the Portuguese islands (Madeira and the Azores) from this study. Sera were collected in 2002 from individuals attending health clinics throughout the 18 districts of Portugal. Levels of neutralizing antibodies against poliovirus types 1, 2 and 3 were determined and a titre of > or = 1:8 was defined as indicative of protected immunity. Results were expressed in international units. The antibody prevalence and the geometric mean antibody concentration (GMAC) was 91.6% (GMAC: 2.96 IU/ml), 94.2% (GMAC: 5.03 IU/ml) and 75% (GMAC: 0.53 IU/ml) for poliovirus types 1, 2 and 3, respectively. For poliovirus types 1 and 2, antibody prevalence was close to or above 90% in the majority of age groups. For poliovirus type 3, antibody prevalence was below 80% in teenagers and young adults. Our study shows that the Portuguese are well protected against poliovirus types 1 and 2. For poliovirus type 3, the suboptimal antibody levels observed in teenagers and young adults suggest the need for a booster dose to minimise the risk of wild poliovirus importation.

Immunologic Considerations for the Timing of the Booster Dose of 7-Valent Pneumococcal Conjugate Vaccine in Young Children

The booster (fourth) dose of 7-valent pneumococcal conjugate vaccine (PCV7) is recommended to be given at 12-15 months but in Canada it better fits the national schedule at 18 months, prompting this comparison of the safety and immunogenicity of booster immunization at 15 or 18 months. Children who had completed a study of primary PCV7 immunization (with final serology at 7-8 months of age) were enrolled at 12 months, bled and randomly assigned to receive a PCV7 booster at age 15 or 18 months, with serologic testing before and 4 weeks afterward. Adverse events were documented for 3 days postbooster. Antibody concentrations were measured for the 7 pneumococcal serotypes and Haemophilus influenzae type b at 7-8, 12, 15 or 18 months and after boosting. Three hundred thirty-one children were boosted, 167 at 15 months and 164 at 18 months. Pneumococcal geometric mean antibody concentrations declined by 15 months to 23.4% of peak geometric mean concentrations at age 7-8 months and to 19.8% by 18 months. Spontaneous increases in 1 or more antibody concentrations were noted in 195 subjects (61.7%), most commonly with types 6B and 19F. Antibody responses to PCV7 were similarly brisk at 15 and 18 months. Mild injection-site redness and swelling were significantly more frequent at 15 than 18 months but no other differences in reactogenicity were observed. Residual antibody concentrations differed minimally between 15 and 18 months. Spontaneous antibody increases often occurred before boosting, possibly from colonization. PCV7 booster vaccination at 18 months appears to be safe and provides comparable immunogenicity to 15 months vaccination.

Effects of housing conditions on the welfare of lactating ewes

Space allocation and housing conditions are critical factors for health and welfare of housed animals and it is well known that sheep are less easily accustomed to confinement than other farmed animals. This study was undertaken to investigate changes in the behavioral, immune and production performances of lactating ewes when subjected to different housing conditions. A one-year trial (from May 2005 to May 2006) was performed with 45 Comisana ewes. At the beginning of the trial the ewes were divided into three groups of 15 each, which were separately penned in the same building and balanced in terms of age, body weights and time of lambing. The treatments were: i) high stock density (HD) with individual ewe having 1.5 m2, ii) low stock density (LD) with individual ewe having 3 m2, iii) low stock density with external paddock (LDP) with individual ewe having 3 m2 divided into 1.5 m2 inside the building and 1.5 m2 in the external paddock. The cell-mediated immune status of sheep was evaluated by means of skin-tests which were performed on all the animals at the beginning of the trial, and then during the dry period, the first phase of pregnancy, the transition period and the beginning of lactation. Chicken egg albumin (OVA) was injected subcutaneously in both shoulders of each ewe to assess the humoral immune response. Antibody titers to OVA were determined in blood samples collected immediately before the first antigen injection and then at 20, 40, 60 and 80 days of the study period by an ELISA performed in 96-well U-bottomed microtiter plates. Behavioral observations were recorded once monthly by two trained observers equipped with video cameras. Scan samples were taken every 15 min from 0830 to 1230 and from 1330 to 1730. After lambing and weaning of lambs, the ewes were machine milked twice daily and milk yield was recorded daily by means of graduated measuring cylinders. Milk samples, consisting of proportional volumes of morning and evening milk, were individually collected weekly in 200 ml sterile plastic containers after cleaning and disinfection of teats (70% ethyl alcohol) and discharging the first streams of foremilk. Samples were carried to our laboratory by means of transport tankers at 4 °C, and analyzed for their chemical composition. Data were processed by analysis of variance, using the GLM procedure of SAS. Cell mediated immune responses detected in LDP ewes were higher than LD responses (P < 0.001). Mean antibody concentration was higher in LDP ewes than in LD ewes (P < 0.05), and in LD than in HD ewes (P < 0.001). A higher number of LDP ewes was observed standing and drinking than LD ewes (P < 0.001 and P < 0.01, respectively). Higher proportions of LD than HD ewes were observed in ambulatory activity (P < 0.01). On the contrary, lower proportions of LD than HD were observed drinking (P < 0.01); a tendency in higher number of aggressive activities was recorded in HD than in LD ewes (P < 0.1). Milk yield was lower in HD than in LD ewes (P < 0.05); milk from HD animals displayed and Somatic Cell Count (SCC) than milk from LD ewes (P < 0.001 and P < 0.05, respectively). Milk from LDP ewes had higher protein and whey protein contents (P < 0.05), and contained more lactose and less SCC than milk from LD ewes (P<0.01 e P<0.05, respectively). Data from the present trial showed that a stocking density of 1.5 m2/animal negatively influenced ewe welfare and production performance.

Antibody prsistence after Haemophilus influenzae type b (Hib) primary vaccination and response to boosters in Korean children

Purpose : Antibody persistence after primary series of Haemophilus influenzae type b (Hib) vaccine and responses to boosters are seldom studied in Korean children. We performed this study to evaluate the antibody titer in relation to booster immunization of Hib vaccine in Korean children. Method : One hundred forty four children aged 12-23 months were enrolled in three university hospitals. The immunogenicity of boosters with Hib vaccine was assessed in children previously primed with Hib vaccine. Antibody persistence was also assessed in children who had received 3 doses of Hib vaccine without a booster. Anti-polyribosylribitol phosphate (PRP) IgG antibody levels and bactericidal titers were determined by enzyme immunoassay and bactericidal assay at the Center for Vaccine Evaluation and Study, Medical Research Institute, Ewha Womans University. Results : Prior to a booster in the second year of life, geometric mean antibody concentrations were 2.39μg/mL and the percent of subjects who had a anti-PRP antibody level 1μg/mL was 68.6%. After boosting, antibody concentration was 19.09μg/mL and the percent of subjects who had a anti- PRP antibody level 1μg/mL was 96.5%, which reflects previous immune priming. In subjects who had finished primary immunization only, the bactericidal titer was 3,946 and in subjects who had a booster, it was 11,205. Anti-PRP antibody level was correlated with serum bactericidal titer. Conclusion : Many children aged 12-23 month old still had protective antibodies after recommended primary immunization only. A booster dose seemed to induce good anamnestic antibody responses in Korean children.

Oral pathogens and allergic disease: Results from the Third National Health and Nutrition Examination Survey

The hygiene hypothesis contends that fewer opportunities for infection have led to increases in the prevalences of asthma and other allergic diseases. This study evaluated the association between asthma, wheeze, and hay fever and antibodies to 2 oral bacteria associated with periodontal disease. Data were obtained from the Third National Health and Nutrition Examination Survey. Serum levels of IgG antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were quantified by enzyme-linked immunoassays in 9385 subjects age 12 years and older. The outcomes were current asthma, wheeze, and hay fever. Odds ratios (ORs) representing a 1-log-unit increase in IgG concentrations were estimated with logistic regression. ORs were adjusted for 8 confounders and weighted to represent the US population. For each disease outcome, geometric mean antibody concentrations were higher in persons without the disease outcome than with the disease outcome. For a 1-log-unit increase in P gingivalis antibody concentration, adjusted ORs were 0.41 (95% CI, 0.20-0.87) for asthma, 0.43 (0.23-0.78) for wheeze, and 0.45 (0.23-0.93) for hay fever. For A actinomycetemcomitans, those ORs were 0.56 (0.19-1.72), 0.39 (0.17-0.86), and 0.48 (0.23-1.03), respectively. Consistent with the hygiene hypothesis, higher concentrations of IgG antibodies to P gingivalis were significantly associated with lower prevalences of asthma, wheeze, and hay fever, and higher concentrations of IgG antibodies to A actinomycetemcomitans were significantly associated with a lower prevalence of wheeze. Colonization of the oral cavity by bacteria and other microbes might play a protective role in the etiology of allergic disease.

Valor diagnóstico do anticorpo antipeptídeo citrulinado cíclico na artrite reumatóide

INTRODUCTION: Rheumatoid arthritis (RA) is one of the most common autoimmune rheumatic diseases, but a specific and reproducible test for its diagnosis is still lacking. OBJECTIVES: To evaluate the diagnostic efficiency of a new commercial ELISA kit in detecting anti-cyclic citrullinated peptide antibodies (anti-CCP) for the diagnosis of RA. METHODS: Anti-CCP antibodies and rheumatoid factor (RF) were determined in the serum of 486 patients: 100 patients with RA and 386 controls, including healthy subjects, patients with other non-rheumatic and rheumatic disease, as well as patients with infections disease. Comparative evaluation of diagnostic performance of anti-CCP and RF was done by calculation the several diagnostic indexes and construction of the ROC (receiver operator characteristic) curve. Statistical analysis included chi-square, Fisher exact, and Mann-Whitney's test. RESULTS: At cutoff of 25 UI/ml, anti-CCP showed sensitivity of 68% (95% CI, 57,8-76,8%), specificity of 97,7% (95% CI, 95,5-98,8%), positive predictive value (VPP) of 88,3% (95% CI, 78,5-94,2%), negative predictive value (VPN) of 92,2% (95% CI, 89-94,5%) and likelihood ratios (LR) of 29,2% (95% CI, 15,1-56,4%). Anti-CCP-positive RA patients had a mean antibody concentration of 920,7 UI/ml (range, 70,5-2000 UI/ml). Anti-CCP-positive non-RA patients had a mean antibody concentration of 38,7 UI/ml (range, 29,5-47, 4 UI/ml). The diagnostic performance of anti-CCP, as estimated by the ROC curve, was superior to that of RF. RF had a higher sensitivity (91%) and a lower specificity (78,8%) than anti-CCP. When the two antibodies were used together, specificity was 99,5%. CONCLUSION: The anti-CCP testing presented the best diagnostic performance for RA and was the most specific test. It may be useful if performance concomitantly with RF in the diagnostic difficulty.

Combined Typhoid Fever and Hepatitis A Vaccine: Comparison of Immunogenicity and Safety to Concomitant Monovalent Vaccine over 3 Years

The safety and immunogenicity of Viatim, a combined hepatitis A (HA) and typhoid fever (Vi) vaccine, were compared with the monovalent component vaccines up to and 1 month after a booster dose at 3 years. Healthy, adult volunteers were randomized to receive Viatim (group A, n = 179) or separate HA and Vi vaccines (group B, n = 181); subgroups were boosted after 3 years with Viatim (groups C and D, n = 56 and 46, respectively). Local and systemic reactions were recorded for 28 days postvaccination. Seroconversion and seroprotection rates and geometric mean antibody concentrations were measured at 14 and 28 days, 1, 2, and 3 years postvaccination, and 28 days after the booster dose. Local and systemic safety profiles were equivalent between the two groups. Immediate local reactions were infrequent (1 in group A and 2 in group B). Local reactions, consisting mostly of mild or moderate pain, were least frequent with monovalent HA. Antibody concentrations to both antigens were similar in groups A and B, in which HA seroprotection rates (> or = 20 mIU/mL) were respectively, 98.7% and 100% at day 28, and 99.1% and 99.0% after 3 years, achieving 100% after the booster. Vi seroprotection rates (> or = 1 microg/mL) of 85.2% and 84.9% after 28 days fell to 32.1% and 35.6% after 3 years, increasing to 67.3% and 69.8% after the booster dose. The combined HA/Vi vaccine, Viatim, had equivalent tolerability and safety and was as rapidly immunogenic as its component monovalent vaccines when given concurrently. A booster dose after 3 years significantly increased antibody levels with some evidence of relative hyporesponsiveness of the typhoid response.

Immunogenicity and effectiveness of Haemophilus influenzae type b conjugate vaccine in HIV infected and uninfected African children

The quantitative (anti-Hib capsular polysaccharide antibody concentrations; anti-HibPS) and qualitative (bactericidal activity and avidity) aspects in immune responses to Haemophilus influenzae type b polyribosyl ribitol phospshate-CRM 197 conjugate vaccine (HibCV; HibTiter ®) were evaluated in 66 HIV infected children not receiving anti-retroviral therapy and 127 HIV uninfected children. Surveillance was conducted for invasive Hib disease in a cohort of 39 865 (approximately 6.4% of whom were HIV infected) children from March 1998 to June 2004. HIV infected children had lower anti-HibPS geometric mean antibody concentrations 1 month post-immunisation than HIV uninfected children ( P < 0.00001) and were less likely to have anti-HibPS antibody concentrations of ≥1.0 μg/ml (RR 0.54; 95% CI 0.43–0.69). A lower proportion of HIV infected children than HIV uninfected children (RR 0.78; 95% CI 0.66–0.93) had measurable anti-Hib serum bactericidal activity (SBA) and the HibPS antibody concentration required for 50% killing of Hib bacteria was greater among HIV infected than HIV uninfected children ( P = 0.001). The estimated risk of HibCV failure was 35.1-fold greater (95% CI 14.6–84.6) amongst HIV infected than HIV uninfected children.

A Prospective Study of 1038 Pregnancies on the Predictive Value of Anti‐Annexin V Antibodies for Fetal Loss

Retrospective studies have demonstrated that anti-annexin V (anti-AnxV) antibodies are linked to miscarriage. Their predictive value is, however, unknown. We have carried out a prospective study to evaluate the relationship between anti-AnxV antibodies and the pregnancy outcome. A serum sample was taken from 1038 consecutive healthy women at the beginning of pregnancy. IgG and IgM anti-AnxV antibodies were measured by an ELISA method. The cutoff value was set at 5 units for both IgG and IgM. Out of 1038 women, 116 (11.4%) had a miscarriage by the 22nd week; 10 were lost to follow-up, 10 had an induced abortion, 6 had a preterm delivery, and 896 carried their pregnancy through to term. An adverse outcome of the pregnancy proved to be directly related to the number of previous miscarriages (P = .008) and the age of the woman (P = .002). IgG and IgM anti-AnxV were present in 25% and 27% of the women who miscarried, and in 23% and 28% of those who gave birth (mean antibody concentration IgG, 4.2 vs. 4.4 U/mL; IgM, 3.7 vs. 3.5 U/mL). IgG and IgM anticardiolipin and anti-beta(2)GPI, together with antinuclear, antithyroperoxidase, and antithyroglobulin antibodies, were also measured in the 116 sera of the women with miscarriage and in an equal number of women who gave birth. Their positivity or level proved not to be useful in discriminating between the risk of miscarriage and term delivery. This large-scale prospective study demonstrates that the presence of IgG and IgM anti-AnxV antibodies, when measured in healthy women, does not give a positive predictive lead towards the possibility of a miscarriage, and it is not useful in evaluating the risk of miscarriage at the beginning of pregnancy.

Quantitative and Qualitative Antibody Response to Pneumococcal Conjugate Vaccine Among African Human Immunodeficiency Virus-Infected and Uninfected Children

To determine the quantitative and qualitative antibody responses to a pneumococcal conjugate vaccine (PnCV) in human immunodeficiency virus (HIV)-exposed infected and uninfected children. Children were randomized to receive either a PnCV or placebo at 6, 10 and 14 weeks of age. PnCV serotype-specific antibody concentrations were measured by a standard enzyme immunoassay (EIA) and a 22F modified EIA (22F EIA) on single serum samples drawn at 21-42 days post-dose 3. Functional activities of the serotype-specific antibody to serotypes 6B, 19F and 23F were measured with an opsonophagocytic assay (OPA). The geometric mean antibody concentrations (GMC) were similar in HIV-infected and HIV-uninfected PnCV recipients for 7 of the 9 vaccine serotypes. In placebo recipients, the GMCs were significantly higher in HIV-infected than in uninfected children for 7 of the serotypes. In HIV-infected PnCV recipients, the GMCs were lower for 5 of the serotypes in children with severe acquired immunodeficiency syndrome than in children who were asymptomatic or mildly symptomatic with acquired immunodeficiency syndrome. HIV-infected PnCV recipients were less likely to have measurable functional antibody (OPA titer > or =1/8) to all 3 studied serotypes (6B, 19F and 23F) than in HIV-uninfected children. HIV-infected children required a higher concentration of anticapsular antibody to achieve 50% of the maximum uptake of labeled Streptococcus pneumoniae in the OPA assay than HIV-uninfected children for 2 of the 3 serotypes, although this was significant only for serotype 6B (P = 0.0005). HIV-infected children have similar quantitative antibody responses but poorer qualitative antibody responses to the PnCV.

Reduced-antigen-content-diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine as a booster for adolescents 10 to 14 years of age

High rates of pertussis disease in adolescents suggest that additional boosting against pertussis would be beneficial. A combined acellular-pertussis-containing booster vaccine (dTpa-IPV; Boostrixtrade mark Polio, n =440) was compared to separately administered dTpa (Boostrixtrade mark) and inactivated polio virus (IPV; Imovax Polio((R)), n =219), and to DTPa-IPV (Infanrixtrade mark IPV, n =111) vaccine in a partially blind, randomised controlled trial in 10-14 year olds. One month after vaccination, seroprotection/seropositivity rates for all antigens were similar for all groups. Although pertussis and diphtheria antibody geometric mean antibody concentrations were higher after DTPa-IPV, all subjects had protective antibodies against diphtheria, tetanus and polio, and at least 97% had a vaccine response to pertussis antigens. Reactogenicity of dTpa-IPV was comparable to dTpa + IPV, but dTpa-IPV was generally better tolerated than DTPa-IPV. The combined reduced-antigen-content-diphtheria-tetanus-acellular-pertussis and IPV vaccine is immunogenic and well tolerated when administered to adolescents and could be used to improve the control of pertussis disease in this age group.

Duration of protective antibodies and correlation with survival in Nile tilapia Oreochromis niloticus following Streptococcus agalactiae vaccination

Streptococcus agalactiae is a major piscine pathogen that causes significant morbidity and mortality among numerous species of freshwater, estuarine and marine fishes. Considering the economic importance of fishes susceptible to S. agalactiae throughout the world, an efficacious S. agalactiae vaccine was developed using an extracellular product (ECP) fraction and formalin-killed whole cells of S. agalactiae. A vaccine study was conducted by intraperitoneal (i.p.) injection in Nile tilapia Oreochromis niloticus in order to determine the duration of protection and its correlation to antibodies specific for this pathogen. After 47, 90 or 180 d post-vaccination (DPV), the fish were i.p. challenged with approximately 2.0 x 10(4) S. agalactiae colony-forming units (CFU) fish(-1) to determine the duration of protective immunity. The percent survival in control fish i.p.-injected with sterile TSB was 16,16, and 4% on 47, 90 and 180 DPV, respectively, while the percent survival for the vaccinated fish was 67, 62 and 49%, respectively. The specific mean antibody concentration of the vaccinated fish was significantly higher than that of the control fish, with significant correlation between the ELISA optical density (OD) and protection. These results indicate that the specific antibody has a correlation with protection following immunization with the S. agalactiae vaccine and that the vaccine can confer protection against S. agalactiae up to 180 DPV.

Dose response of CRM 197 and tetanus toxoid-conjugated Haemophilus influenzae type b vaccines

High vaccine cost has limited use of conjugate vaccines in the developing world where the disease burden is greatest. Fixed fractional doses of Haemophilus influenzae type b (Hib) vaccines have been shown to be immunogenic, but dose responses of these vaccines in humans are needed to determine the lowest immunogenic dose as an option for lowering vaccine cost. We randomized children to receive one of five doses (0.625, 1.25, 2.5, 5.0 and 10 μg) of either a diphtheria CRM 197 or tetanus toxoid-conjugated Hib vaccine. The children received a primary three-dose series at 6, 10, and 14 weeks of age and a booster dose at 9 months. Anti-PRP IgG antibodies were measured at each vaccination, at 18 weeks, and at one week following the booster dose. Concentrations of ≥1.25 μg of HibCRM 197 vaccine produced mean anti-PRP responses at 18 weeks of ≥5.72 μg/ml and ≥0.15 μg/ml was achieved in >98% of the children with at least 79% reaching anti-PRP concentrations of ≥1.0 μg/ml. Concentrations of ≥1.25 μg of Hib-tetanus vaccine produced mean anti-PRP responses at 18 weeks of ≥8.63 μg/ml and ≥0.15 μg/ml was achieved in 100% of the children with at least 88.9% reaching anti-PRP concentrations of ≥1.0 μg/ml. While mean antibody concentrations after either vaccine decreased over time, the proportion of children with antibody levels of ≥0.15 μg/ml had not changed significantly at the 9 month measurement. Immunologic memory was demonstrated by significant increases in mean antibody concentrations one week after the booster dose for doses ≥1.25 μg of HibCRM 197 and Hib-tetanus to mean concentrations ≥37.71 and 16.07 μg/ml, respectively. There were no differences in antibody responses for vaccine doses ≥1.25 μg of the same vaccine or between the same concentrations of the two different vaccines. Our data suggest that doses of these vaccines of ≥1.25 μg may be sufficient to stimulate an immune response that offers both short and longer term protection from invasive Hib disease.

Characterization of antibodies to PspA and PsaA in adults over 50 years of age with invasive pneumococcal disease

We characterized antibody responses to two Streptococcus pneumoniae surface proteins, PspA and PsaA, in 14 adults over 50 years of age hospitalized with invasive pneumococcal disease (IPD), and in two groups of age-matched controls (18 patients with invasive disease due to other microorganisms and 35 patients hospitalized for non infectious conditions). All patients with IPD and all control subjects had detectable antibodies to both proteins on hospital admission. Three weeks later, the geometric mean concentrations of antibodies to PspA and PsaA in IPD patients were respectively 10 and 25 times higher than on admission. In contrast, acute and convalescent antibody levels were similar in control patients with invasive diseases due to other microorganisms.

Antibody persistence, PRP-specific immune memory, and booster responses in infants immunised with a combination DTPa–HBV–IPV/Hib vaccine

A new single-injection combination vaccine against six diseases has been developed to accommodate the growing number of recommended paediatric vaccines. A pentavalent liquid diphtheria, tetanus, acellular pertussis (3-component), hepatitis B, and inactivated polio (types 1–3) combined vaccine (DTPa–HBV–IPV) is extemporaneously mixed with a lyophilized Haemophilus influenza type B (Hib) conjugate vaccine (polyribosyl-ribitol phosphate (PRP)–T) and given as a single-injection. A cohort of 368 healthy infants was initially studied to evaluate the immunogenicity and reactogenicity of this hexavalent combination given as a primary course at 2, 4, and 6 months of age. At 15 months of age, from this cohort, 219 children received a booster dose of a licensed DTPa/Hib (PRP–T) vaccine to assess the booster response, while 70 received a challenge dose of unconjugated PRP (PRP) vaccine (to evaluate Hib-specific memory) plus a separate DTPa vaccine. Seven to 10 days following plain PRP challenge, anti-PRP geometric mean antibody concentrations (GMCs) had increased 13-fold to 5.67 μg/ml, and thirty days after conjugated PRP booster vaccination, anti-PRP antibody GMCs increased 102-fold. Both responses are indicative of immune memory. Vaccination was well tolerated following all primary and booster doses, although 10.5% of booster recipients experienced >50-mm local swelling at the site of DTPa vaccination. We conclude that DTPa–HBV–IPV/Hib is safe and immunogenic for primary vaccination, and that Hib-specific memory is induced by primary vaccination.

Immunogenicity, reactogenicity and adherence with hepatitis A vaccination among drug users

Hepatitis A virus (HAV) vaccination is recommended in drug users (DUs) because this population has a very high prevalence of hepatitis C virus, and additional infection with HAV can lead to increased morbidity and mortality. The efficacy of hepatitis A vaccine (1440 ELISA units), in terms of immunogenicity, reactogenicity and compliance among 44 heroin DUs using a 0–6 month schedule was investigated. Three subjects (6.8%) experienced adverse reactions. After the first dose of hepatitis A vaccine, 37% of subjects seroconverted. Two months after the 6-month booster vaccination, all vaccinated patients became seropositive. The mean serum antibody concentration was 40 mIU/ml after 6 months and 558 mIU/ml after 8 months. Although all DUs proved seropositive after the booster vaccination, the seroconversion rate, at the 2 and 6 months time points was much lower than in healthy subjects. The lower geometric mean titre could affect the kinetics of decrease of antibody titres and the protection conferred by vaccination may be less durable in these patients. These findings indicate that the 0–12 months schedule could be reduced to a shorter 0–6 months schedule in order to shorten the unprotected period. Further studies among drug users are needed to explore the efficacy and immunogenicity of higher doses or alternative schedules of HAV vaccine.

Commercial immune globulin, intravenous (IGIV) products contain anti-vaccinia antibodies

Rationale Individuals with immune deficiency diseases may be at risk for vaccinia infection if widespread smallpox immunization programs are implemented in the U.S. for bioterrorism preparedness. Through inadvertent vaccination or contact with an infectious immunization site, immune deficient individuals could sustain morbidity or mortality from complications of vaccinia infection. Passively administered anti-vaccinia antibody-containing immune globulins can prevent or attenuate widespread vaccinia infection. Long-lasting antibody responses in blood or plasma donors could supply anti-vaccinia antibodies. In this study, we evaluated currently licensed IGIV products to determine whether they contain biologically active anti-vaccinia antibodies. Methods Eight licensed and two investigational IGIV products were tested in a vaccinia plaque reduction neutralization assay. Three lots of each product were tested and compared to a reference vaccinia immunoglobulin (VIG, positive control) and a commercially available 5% albumin product (negative control). Five of these lots were randomly selected to determine in vivo activity in SCID mice. Results All tested products contained anti-vaccinia antibodies when compared to the VIG standard in vitro. The mean antibody concentration that neutralized 50% of plaques was 0.413 mg/mL. In vivo, all IGIVs delayed mortality in vaccinia-inoculated SCID mice compared to untreated mice. Conclusions Commercial immune globulins contain anti-vaccinia antibody activity. Compared with VIG, the titers were lower, as would be expected. Since IGIV doses for immune deficient patients are four to eight fold higher than recommended VIG doses, use of IGIV may provide some protection for individuals with inherited or acquired immune deficiencies if they are exposed to vaccinia.

PK modeling and simulations of an anti IL-6 MAB in patients with renal cell carcinoma

Purpose To employ PK modeling and clinical trial simulations for the selection of an appropriate dosing regimen for a Phase I/II clinical study to assess the therapeutic potential of an anti-IL-6 mAb in patients with metastatic renal cell carcinoma (RCC) following single ascending IV infusions. Methods: PK modeling and trial simulations were conducted using WinNonlin and Trial Simulator software. The model was developed using published data from patients with advanced multiple myeloma (van Zaanen, 1996). Results: Since IL-6 is a critical mediator in the pathophysiology of RCC, the dosing regimen for this study was selected based on neutralizing the blood level and endogenous production of IL-6. A minimum of a 300-fold molar excess of mAb to IL-6 was determined to be needed to fully block IL-6 bioactivity and inhibit tumor growth. This equates to a trough mAb concentration of 5 μg/mL. PK modeling and simulations predicted that doses of 1, 3, and 6 mg/kg administered on weeks 0, 3, 6, and 9 would result in mean serum antibody concentration exceeding the target trough concentration of 5 μg/mL for approximately 29, 33, and 35 weeks after the first infusion, respectively. Conclusions: PK modeling and simulations of published data from previous human experience should provide a sound rationale for selecting the appropriate dosing regimen for assessing the therapeutic potential of this study agent, in patients with renal cell carcinoma. Clinical Pharmacology & Therapeutics (2004) 75, P84–P84; doi: 10.1016/j.clpt.2003.11.323

Helicobacter pylori seroprevalence in patients with lung cancer.

To assess Helicobacter pylori (H pylori) seroprevalence in a cohort of Greek patients with lung cancer. Seventy-two lung cancer patients (55 males and 17 females, aged 58.2+/-11.7 years) and 68, age and gender-matched, control subjects were enrolled. All subjects underwent an enzyme-linked immunosorbent assay IgG serologic test for H pylori diagnosis. A correlation between age and H pylori IgG level was detected for both lung cancer patients (r = 0.42, P = 0.004) and controls (r = 0.44, P = 0.004). Seropositivity for H pylori did not differ significantly between patients with lung cancer and controls (61.1% vs 55.9%, P>0.05). Concerning the mean serum concentration of IgG antibodies against H pylori, no significant difference between the two groups was detected (32.6+/-19.1 vs 27.4+/-18.3 U/mL, P>0.05). No significant association between H pylori infection and lung cancer was found.