Biomedical subjects

K Reisinger

Publications and source records attributed to K Reisinger.

14 recordsLinked to original sources

PubMed2001

Safety and immunogenicity of four doses of Neisseria meningitidis group C vaccine conjugated to CRM197 in United States infants.

BACKGROUND: Following widespread use of conjugate pneumococcal vaccine, Neisseria meningitidis likely will become the leading cause of bacterial sepsis and meningitis in US children. This report describes the safety and immunogenicity in US children of four consecutive doses of a meningococcal group C vaccine conjugated to CRM197 via reductive amination (MnCC). METHODS: One hundred six healthy 2-month-old infants received MnCC at 2, 4 and 6 months of age in a randomized, controlled double blind study; children in the other treatment arm were given a 7-valent conjugate pneumococcal vaccine. Parents reenrolled 64 of these children at 12 to 15 months to receive a fourth dose of MnCC. Routine childhood vaccines, including DTP, were coadministered. Temperatures and symptoms were recorded for 3 days after each immunization. Serum enzyme-linked immunosorbent assay IgG and bactericidal antibodies were measured prevaccination and before and 1 month after Doses 3 and 4. RESULTS: Moderate to severe local reactions, defined as erythema or induration > or =2.4 cm or pain that interfered with limb movement was reported after 0 to 3.2% of MnCC injections, depending on the reaction and dose. Fever occurred in 23 to 37% of children, but the contribution of MnCC to the febrile reactions is unknown. Geometric mean concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72 microg/ml after Dose 3 and 8.03 microg/ml after the booster. Geometric mean functional serum bactericidal antibody titers after Doses 3 and 4 were 1:463 and 1:2341, respectively. One hundred percent of children had a serum bactericidal antibody titer of > or =1:64 after three doses and > or = 1:128 after the booster. CONCLUSIONS: The MnCC vaccine had an acceptable safety profile and generated high titers of bactericidal antibody in immunized US infants and toddlers. It appears to be an attractive candidate vaccine for the prevention of serogroup C meningococcal disease in young children.

Antibodies, Bacterial↗

PubMed2000

Randomized multicenter trial documenting the efficacy and safety of a lactose-free and a lactose-containing formula for term infants.

OBJECTIVE: To evaluate the efficacy and safety of a new lactose-free infant formula. DESIGN: Randomized, prospective, double-blind, controlled, outpatient, multicenter, parallel 12-week trial. SETTING: Ambulatory-care facilities of the participating centers. SUBJECTS: 137 healthy term infants (approximately 7 days old at the time of study enrollment). INTERVENTION: Healthy term infants, whose mothers had decided not to breast-feed, were randomly assigned 1 of the 2 study formulas. MAIN OUTCOME MEASURES: Weight, length, and occipitofrontal circumference measurements were obtained at baseline and when the infant was 2, 4, 8, and 12 weeks old. Formula acceptance and tolerance were also assessed at weeks 2, 4, 8, and 12. Serum albumin concentration, creatirune level, and blood urea nitrogen were determined at baseline and week 12. Adverse events were assessed throughout the study. STATISTICAL ANALYSES PERFORMED: Each baseline anthropometric and laboratory variable was analyzed for comparability between groups using the Student t test and was also analyzed using a repeated-measures analysis of variance method. Covariance analysis was applied to the final laboratory data using the respective baseline data as covariates. Decisions about equality of mean responses to formula effects were based on the .05 level of significance in all cases. RESULTS: One hundred four infants completed the study. No significant differences between the 2 formula groups were noted for any of the growth and blood parameters. APPLICATIONS: This new formula is an effective and safe lactose-free nutrition alternative for infants who require such a diet.

Anthropometry↗

PubMed2000

Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.

Administration, Intranasal↗

PubMed2000

Ultraviolet-A-induced transactivation of the vascular endothelial growth factor gene in HaCaT keratinocytes is conveyed by activator protein-2 transcription factor.

Ultraviolet-A radiation represents a significant proportion of the ultraviolet solar spectrum that was recently shown to affect gene expression of epidermal keratinocytes by molecular mechanisms distinct from ultraviolet-B radiation. As ultraviolet-A either alone or in combination with ultraviolet-B may contribute to photocarcinogenesis, we aimed to explore the biologic effects of ultraviolet-A radiation on vascular endothelial growth factor gene expression by the immortalized keratinocyte cell line HaCaT. As keratinocyte-derived vascular endothelial growth factor not only provides the major cutaneous angiogenic activity but may also augment the malignant phenotype of tumor cells, we studied the molecular mechanisms of ultraviolet-A-induced vascular endothelial growth factor expression in HaCaT cells, serving as a transformed preneoplastic epithelial cell line. Whereas ultraviolet-B-mediated vascular endothelial growth factor expression has been previously indicated to be conveyed by indirect mechanisms, ultraviolet-A rapidly induced vascular endothelial growth factor mRNA expression in a fashion comparable to that seen with the transforming growth factor alpha, representing a direct and potent activator of vascular endothelial growth factor gene transcription. Ultraviolet-A was found to readily induce vascular endothelial growth factor promoter-based reporter gene constructs through a consensus element for activator protein-2 transcription factor. The critical role of activator protein-2 was substantiated by demonstration of ultraviolet-A-induced activator-protein-2-dependent nuclear DNA binding activity to this site, and by inhibition of ultraviolet-A-mediated vascular endothelial growth factor gene transcription through insertion of a critical mutation within the activator protein-2 sequence. Together, our data further elucidate photobiologic aspects of ultraviolet-A-induced gene expression by characterizing mechanisms of vascular endothelial growth factor upregulation at the molecular level. In addition, our experiments support the concept of a more general importance of activator protein-2 in ultra- violet-A-mediated responses by keratinocytes or keratinocyte-derived cell lines.

Base Pairing↗

PubMed2000

Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine.

The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.

Administration, Intranasal↗

PubMed2000

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Journal Article↗

PubMed1999

Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial.

BACKGROUND: Rotavirus is the most common cause of severe, dehydrating diarrhoea in infants worldwide. We assessed the safety, immunogenicity, and efficacy of a live, oral human rotavirus vaccine, 89-12, in US children in a randomised, placebo-controlled, double-blind multicentre trial. METHODS: 215 healthy infants were enrolled, of whom 213 were given two doses of 89-12 (containing 1x10(5) plaque-forming units) or placebo, and 213 were followed up through one rotavirus season. The frequency of side-effects was compared for 7 days after each dose of vaccine. Immune responses to rotavirus were assessed by serum and stool IgA, and by serum 89-12 neutralising titres. The primary outcome variable (protection from rotavirus disease) was evaluated by comparing the frequencies of rotavirus gastroenteritis in an intention-to-treat analysis. FINDINGS: Adverse reactions were mild. Low-grade fever (> or = 38.1 degrees C) after the first dose was the only side-effect significantly more common in the vaccine group than in the placebo group (21 [19%] vs 5 [5%], p=0.001). An immune response to vaccine was detected in 94.4% of vaccinees. Rotavirus disease occurred in 18 of 107 placebo recipients and two of 108 vaccine recipients (vaccine efficacy 89.0% [95% CI 65.4-94.5]). Ten infants in the placebo group but none in the vaccine group were presented for medical care. INTERPRETATION: The 89-12 rotavirus vaccine was safe and immunogenic and provided a high degree of protection against rotavirus disease. Further investigations of this vaccine are needed to confirm these findings in other settings.

Administration, Oral↗

PubMed1999

Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.

A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.

Adolescent↗

PubMed1997

Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size on immunogenicity and interactions with simultaneously administered vaccines.

Six pentavalent pneumococcal conjugate vaccines (Pn-CRM197) were evaluated among 400 infants. The vaccines differed in saccharide chain length (oligosaccharide [OS] or polysaccharide [PS]) and saccharide quantity (0.5, 2, or 5 microg). Subjects were randomized into groups 1-6 (Pn-CRM197 recipients) or 7 (controls) for immunization at 2, 4, and 6 months of age. Pn-CRM197 were well tolerated and elicited mean antibody concentrations that exceeded those in controls for all 5 capsular serotypes. PS formulations were generally more immunogenic than their OS counterparts. For PS vaccines, a dose-response was documented (5 microg > 2 microg > 0.5 microg), but the differences between the 5- and 2-microg formulations were insignificant. The mean anti-PRP antibody concentration was significantly higher among Pn-CRM197 recipients. It is concluded that PS vaccines are more immunogenic than OS vaccines. The improved immunogenicity from Haemophilus type b oligosaccharide conjugate (HbOC) vaccine when given with Pn-CRM197 suggests that a decreased dose of HbOC vaccine may be sufficient to elicit protection.

Antibodies, Bacterial↗

PubMed1995

Safety and cellular and humoral immune responses of a booster dose of varicella vaccine 6 years after primary immunization.

Four hundred nineteen children and adolescents immunized with live varicella vaccine 4-6 years earlier were enrolled in a study to evaluate the safety and immune response to a booster dose containing approximately 3300 pfu of virus. Of the subjects, 99% (414/419) maintained antibody to varicella zoster virus (VZV) with a geometric mean titer of 25.7 and mean stimulation index (SI) for VZV-specific lymphoproliferation response of 40.3 +/- 5.3 (SE). Some 7-10 days after the booster immunization, seropositivity rates increased to 100% (302/302), and GMT was 143.6 (anamnestic response). At 6 weeks after the booster inoculation, a subset of subjects had 100% seropositivity (74/74) with a GMT of 218.8 and an SI of 58.6. After 3 months, seropositivity was 100% (358/358), GMT was 119.0, and SI was 61.4.

Adolescent↗

PubMed1995

Safety and immunogenicity of two acellular pertussis vaccines with different pertussis toxoid and filamentous hemagglutinin content in infants 2-6 months old.

The optimal composition and antigen content of acellular pertussis vaccines is not known. Two vaccines with different quantities of pertussis toxoid (10 and 20 micrograms) and filamentous hemagglutinin (5 and 20 micrograms) and identical 69 kD protein (3 micrograms) and fimbriae 2 and 3 (5 micrograms) combined with diphtheria and tetanus toxoids were compared in a randomized, double-blind study in 2,050 infants undergoing their primary immunization series at 8 centers in the US and Canada. A 6:1 increased antigen to lower antigen allocation was used; 96% of infants received 3 doses and completed the study. A 'clinically significant' local reaction was reported in 3-6% of participants after each dose. Erythema was the most common reaction occurring in 3-5% of infants after the second or third dose. A clinically significant systemic adverse reaction was reported in 28-34% of vaccinees (or vaccinated children) after each dose; fever (7-18%) and fussiness (12-17%) were most common. There were no differences in adverse events between the 2 vaccine formulations. Antibody responses were measured in 292 infants at 1 center. At 7 months, geometric mean anti-filamentous hemagglutinin antibody titers were higher in recipients of the higher antigen content vaccine (p < 0.001) whereas recipients of the lower antigen content formulation had higher anti-fimbriae antibody (p < 0.001) and agglutinin titers (p < 0.05). No differences were detected in anti-pertussis toxin or other antibody responses between the formulations. We conclude that increasing the antigen content of the acellular pertussis vaccine had a variable effect on antibody response but was not associated with increased adverse reactions.

Adhesins, Bacterial↗

PubMed1993

Inactivated hepatitis A vaccine in childhood: implications for disease control.

The experience to date with the Merck inactivated hepatitis A vaccine in healthy children 2-16 years old is reviewed. Comparison of response to increasing doses indicates that an intramuscular dose of 25 units results in seroconversion of 99% of children by week 4 following a single dose. Antibody persistence rate is nearly 100% six months later, whether or not a second priming dose is given at week 8. This vaccine has proven highly immunogenic in children and has a favourable safety/tolerability profile. It should be useful for pre-exposure prophylaxis and control of hepatitis A, and should eventually replace immune globulin (Ig) for this indication.

Adolescent↗

PubMed1992

Safety and immunogenicity of acellular pertussis vaccine combined with diphtheria and tetanus toxoids in 17- to 24-month-old children.

A double-blind, randomized, controlled trial comparing 4 lots of acellular pertussis-diphtheria tetanus toxoids vaccine (APDT) to whole cell DTP vaccine in 397 children was conducted at 7 clinical centers. Children were immunized at 17 to 24 months of age and sera were obtained pre- and postimmunization. Sera were analyzed for antibody to pertussis antigens (pertussis toxin, filamentous hemagglutinin, with a molecular weight of 69,000 (69k) outer membrane protein and agglutinogens) and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events was collected daily for 10 days postimmunization. The acellular vaccine produced significantly fewer local reactions than whole cell DTP. Parents reported that drowsiness or fretfulness occurred significantly less often in APDT vaccine recipients compared with whole cell DTP recipients. Fever greater than or equal to 38.3 degrees C occurred in 8% of APDT vaccine recipients and in 15% of whole cell DTP vaccine recipients (P = 0.06). The only significant difference in immune response to pertussis antigens between the two vaccines was for filamentous hemagglutinin (P less than 0.01) for which significantly higher antibody concentrations were found in the APDT vaccine group. We conclude that this APDT vaccine is safe and immunogenic when administered as a booster dose to 18-month-old children.

Antibodies, Bacterial↗

PubMedDate not supplied

Acute rheumatic fever and rheumatic heart disease on the Navajo reservation, 1962-77.

The occurrence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Navajos was ascertained for the period from 1962 through 1977 by means of hospital discharge diagnoses and patients' charts. The annualized attack rate for ARF was 12.4 per 100,000 population, with no clear evidence of an overall secular trend. The proportion of recurrences (19.6 percent) and clinical features were similar to those reported elsewhere, but no seasonal variation in attack rates was noted. Between 1962-71 and 1972-77, the age of RHD patients increased, suggesting few newly diagnosed cases and the aging of known patients. A streptococcal disease control program was instituted in many Navajo elementary schools before 1975. In the program, throat cultures were performed routinely for some asymptomatic children and for all symptomatic children. During the subsequent 3 years, ARF rates declined from 13.5 to 8.2 per 100,000 in areas covered by the program, while in the noncovered areas the rates showed little change-9.5 to 10.1 per 100,000.

Acute Disease↗