Milk protein-based infant formula containing rice starch and low lactose reduces common regurgitation in healthy term infants: a randomized, blinded, and prospective trial.

OBJECTIVE: Spit-up (regurgitation) reduction with prethickened milk protein-based infant formulas containing rice starch has been clinically demonstrated in infants with heavy spit-ups but not in otherwise healthy normal infants with common spit-ups. The objective of this study was to evaluate growth, gastrointestinal tolerance, and efficacy to reduce common spit-up in normal, healthy term infants fed an investigational rice starch prethickened lactose-free milk protein-based infant formula. METHODS: This double-blind, randomized, parallel study evaluated the investigational rice starch prethickened lactose-free (low lactose < 100 mg/L) milk protein-based infant formula compared to a standard, commercially available, iso-nutrient, lactose-containing (100% of carbohydrate) milk-based infant formula (control) for growth and gastrointestinal tolerance in healthy term infants (n = 132/group) fed from 14 ± 3 days to 112 days of age. Data were classified and analyzed as evaluable (EV; subjects completing study per protocol) or intent-to-treat data (ITT; all subjects with available data). RESULTS: Growth as indicated by weight gain (primary variable) and formula intake were not significantly different (p > 0.05) between feeding groups (EV or ITT). Though both formulas were well tolerated, spit-up frequency was significantly lower (p < 0.05) in the rice versus control group by 53% at 28 days of age, 54% at 56 days, 48% at 84 days, and 32% at 112 days (EV). Importantly, infants in the rice group were 1.6 to 1.8 times more likely to report zero spit-up than infants in the control group. The rice group also had higher percentages of soft and yellow stools. CONCLUSIONS: The rice starch prethickened lactose-free milk protein-based formula (rice) supported normal growth and safe use as the sole source of feeding for normal infants over the first 4 months of life. The rice formula was efficacious in providing a clinically relevant reduction of spit-up frequency in otherwise healthy term infants.

Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials.

BACKGROUND: Data are needed from large clinical trials of paediatric, adult, and elderly people to find the appropriate antigen dose and vaccination schedule for the 2009 pandemic influenza A H1N1. We therefore report preliminary safety and immunogenicity results after one injection of a licensed monovalent pandemic H1N1 vaccine in the USA. METHODS: We randomly assigned healthy children (aged 6-35 months and 3-9 years) and adults (18-64 years and >or=65 years) to vaccine containing per dose 7.5 microg (children and adults), 15 microg (children and adults), or 30 microg (adults only) haemagglutinin in two placebo-controlled, observer-masked, multicentre phase 2 studies done in the USA. Participants were allocated with an interactive voice-response system or computer-generated randomisation lists with opaque scratchable patches. Primary outcome was haemagglutination inhibition antibody response 21 days after the first of two planned vaccinations (interim analysis of studies in progress). Analyses were by full-analysis set. The trials are registered with ClinicalTrials.gov as NCT00953524 and NCT00952419. FINDINGS: 410 of 423 children and 724 of 750 adults given an active vaccine, and 50 of 51 children and 95 of 99 adults given placebo were assessed for immunogenicity on day 21. After active vaccination, 45 of 101 (45%; 95% CI 35-55) to 47 of 94 (50%; 40-61) infants aged 6-35 months, 75 of 109 (69%; 59-77) to 80 of 106 (75%; 66-83) 3-9-year-old children, 134 of 141 (95%; 90-98) to 144 of 144 (100%; 98-100) of 18-64-year-old adults, and 93 of 100 (93%; 86-96) to 93 of 98 (95%; 89-98) elderly adults were seroprotected (proportion with titres >or=1:40). No vaccine-related serious adverse events occurred. Injection-site and systemic reactions were reported by up to about 50% of every age and vaccine group, with no noticeable differences between vaccine and placebo groups. INTERPRETATION: One dose of vaccine was highly immunogenic in adults, suggesting that it afforded sufficient protection against this pandemic influenza A H1N1 virus. Two doses of vaccine will probably be needed in children younger than 9 years. Safety and reactogenicity of the vaccine were acceptable and similar to those of seasonal vaccine. FUNDING: Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority.

Prevalence of human papillomavirus infection and associated risk factors in young women in Brazil, Canada, and the United States: a multicenter cross-sectional study.

To determine the prevalence of cervical human papillomavirus (HPV) infection and risk factors in young women from Brazil, Canada, and the USA. Cross-sectional study in 3204 healthy women, aged 15 to 25 years. Cervical samples were collected for cytology and for HPV DNA detection (SPF 10-LiPA 25 system). Serum samples were collected for the measurement of HPV-16 and HPV-18 antibodies by enzyme-linked immunosorbent assay. Risk factors were obtained through a questionnaire. Overall, 26.6% of women had DNA detected for at least 1 HPV type. The prevalence for oncogenic HPV types was 21.7% (25% in Brazil, 16.9% in Canada, and 19.1% in the USA). HPV-16 was the most prevalent oncogenic type (5.2%). The next most common oncogenic HPV types were 51 (3.3%), 52 (3.3%), 31 (2.9%), 66 (2.3%), and 39 (2.0%). Multiple oncogenic types were detected in one-third of the infections. The prevalence of HPV-16 and/or HPV-18 infections detected by DNA and/or enzyme-linked immunosorbent assay was 24.8%. The majority of women (85%) had a normal cervical cytology. Sexual behavior was the main determinant for HPV-16/18 infections and squamous intraepithelial lesions. The prevalence of HPV oncogenic infections was high and linked to sexual behavior. Strategies to reduce the burden of oncogenic HPV infection, such as prophylactic vaccination programs, are likely to impact the burden of disease due to cervical precancer and cancer.

Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States.

An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ≥0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.

Immunogenicity and safety of an inactivated hepatitis a vaccine administered concomitantly with a pneumococcal conjugate vaccine in healthy children 15 months of age.

The immunogenicity and safety of hepatitis A vaccine and pneumococcal conjugate vaccine, administered separately or concomitantly in children 15 months of age, were evaluated. After completed vaccinations, antihepatitis A and antipneumococcal geometric mean concentrations were similar across groups. Both vaccines were well-tolerated when given concomitantly during the second year of life.

Immunogenicity and safety of a combination diphtheria, tetanus toxoid, acellular pertussis, hepatitis B, and inactivated poliovirus vaccine coadministered with a 7-valent pneumococcal conjugate vaccine and a Haemophilus influenzae type b conjugate vaccine.

OBJECTIVE: To evaluate the immunogenicity and safety of a diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus-containing vaccine (DTaP-HepB-IPV) coadministered with pneumococcal 7-valent conjugate vaccine (PCV-7) and Haemophilus influenzae type b vaccine (Hib), with separate vaccines concurrently, or staggered (delayed) administration of PCV-7. STUDY DESIGN: At 2, 4, and 6 months of age, infants received either DTaP-HepB-IPV plus PCV-7 and Hib (n = 199), separate vaccines (n = 188), or DTaP-HepB-IPV plus Hib with PCV-7 administered 2 weeks later (n = 188). Blood was drawn before and after vaccination. Parents reported symptoms for 4 days after each dose and adverse events throughout the entire study. RESULTS: Immunogenicity in the Combination Vaccine Group was noninferior to that of the Separate and Staggered Vaccine Groups with respect to seroprotective rates for diphtheria, tetanus, and poliovirus and to geometric mean concentrations for pertussis. Seroprotective rates for HepB and Hib were not different between groups. Seropositivity for PCV-7 was high in all groups. Administration of combination vaccine appeared to be associated with higher rates of irritability, fever > or = 100.4 degrees F (38.0 degrees C) and some local symptoms compared with separate vaccines (exploratory P < .05). No group differences were observed in rates of symptoms for which parents sought medical advice. CONCLUSIONS: DTaP-HepB-IPV was highly immunogenic and well tolerated when coadministered with Hib and PCV-7 at 2, 4, and 6 months of age.

Rapid and sustained immune response against hepatitis A and B achieved with combined vaccine using an accelerated administration schedule.

BACKGROUND: Combined hepatitis A and B vaccine administered on an accelerated schedule provides a rapid immune response against both hepatitis A and B viruses, which might be especially relevant for individuals who need protection quickly. METHODS: A prospective, open-label, randomized study to compare the immunogenicity and reactogenicity of the combined hepatitis A and B vaccine Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) (>or=720 EL.U/mL inactivated hepatitis A antigen and 20 microg/mL recombinant hepatitis B surface antigen [HBsAg]) administered at 0, 7, 21 to 30 days, and 12 months compared with concurrent administration of Havrix [GlaxoSmithKline Biologicals, Rixensart, Belgium (>or=1440 EL.U/mL inactivated hepatitis A antigen)] at 0 and 12 months, and Engerix-B [GlaxoSmithKline Biologicals, Rixensart, Belgium (20 microg/mL recombinant HBsAg)] at 0, 1, 2, and 12 months in seronegative healthy adults. RESULTS: At month 13, the anti-hepatitis B seroprotection rates (>10 mIU/mL) for the combined vaccine compared to the monovalent hepatitis B vaccine were 96.4% (95% CI: 92.7-98.5) and 93.4% (95% CI: 89.0-96.4), respectively. The anti-hepatitis A seroconversion rates were 100% in both groups (95% CI: 98.1-100). At day 37, the anti-hepatitis A seroconversion rates were similar in both groups (98.5% for combined vaccine, 98.6% for the monovalent vaccine group), but the combined vaccine resulted in a statistically significantly ( p < 0.001) better anti-hepatitis B seroprotection compared to monovalent hepatitis B vaccine, 63.2% versus 43.5%, respectively. The reactogenicity profile was similar in both study groups. CONCLUSIONS: The combined hepatitis A and B vaccine administered on an accelerated schedule was at least as immunogenic and as well tolerated as the corresponding monovalent vaccines.

Immune memory in children previously vaccinated with an experimental quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine.

BACKGROUND: In a previous study, a meningococcal diphtheria toxoid conjugate vaccine (MCV-4) triggered robust bactericidal antibody responses against serogroups A, C, Y, and W-135 in 2- to 10-year-old children. A subset of participants, 2 to 3 years of age at the initial vaccination, was evaluated for persistence of antibody, immune memory, and antibody avidity. METHODS: Participants were healthy children vaccinated 23 to 36 months earlier with MCV-4 (primed) or newly recruited meningococcal vaccine-naive 4-year-olds. Participants in both groups were alternately allocated to provide sera 8 or 28 days after administration of one tenth of the recommended dose of a meningococcal polysaccharide vaccine (PSV-4). Immune responses were assessed in sera obtained at baseline and either 8 or 28 days after reduced-dose PSV-4 administration. Safety was monitored. RESULTS: Before PSV-4 challenge, serum bactericidal antibody geometric mean titers (SBA GMTs) were higher for all 4 serogroups in the MCV-4-primed group than in the vaccine-naive group. SBA GMTs, geometric mean concentrations of immunoglobulin G (IgG) and geometric mean avidity indices for all 4 serogroups were significantly higher among MCV-4-primed versus vaccine-naive participants in the cohorts evaluated at 8 or 28 days after PSV-4 challenge. Adverse events were generally mild, self-limited, and comparable in all groups of children. CONCLUSIONS: Persistence of bactericidal antibody was seen for 23 to 36 months after a primary dose of MCV-4 in young children. Booster responses and avidity maturation were evident after a challenge with reduced-dose polysaccharide vaccine.

Incidence and duration of type-specific human papillomavirus infection in high-risk HPV-naïve women: results from the control arm of a phase II HPV-16/18 vaccine trial.

OBJECTIVES: Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners. METHODS: Data were obtained from 553 women (15-25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. Samples were tested for HPV types using a broad-spectrum PCR assay. Incidence rate ratios (RRs) and 95% CIs were used to estimate the association among age, sexual habits and HPV acquisition. RESULTS: Incidence rates (95% CI) using cervical samples were 11.8 (10.4 to 13.4) and 5.6 (4.7 to 6.6) per 1000 women-months for HR-HPVs and low-risk HPVs (LR-HPVs), respectively. Equivalent rates in combined cervicovaginal and cervical samples were 17.2 (15.4 to 19.2) and 6.9 (5.9 to 8.0), respectively. 54 per cent of HR-HPV types from combined cervicovaginal and cervical samples persisted for 1 year compared with 32.3% for LR-HPV types. The risk of acquiring any HPV infection was higher among women aged <21 years (RR=1.33, 95% CI 1.1 to 1.7) and women having >1 sexual partner (RR=1.83, 95% CI 1.4 to 2.4) at baseline. CONCLUSIONS: HR-HPV infections were more common and lasted longer on average than LR-HPV infections. HPV acquisition was more common in younger women with multiple sexual partners. TRIAL REGISTRATION NUMBER: NCT00689741, NCT00120848; Post-results.

Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.

BACKGROUND: Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions. METHODS: We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity. FINDINGS: In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic. INTERPRETATION: The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.

Comparative trial of the safety and immunogenicity of quadrivalent (A, C, Y, W-135) meningococcal polysaccharide-diphtheria conjugate vaccine versus quadrivalent polysaccharide vaccine in two- to ten-year-old children.

BACKGROUND: A quadrivalent meningococcal diphtheria conjugate vaccine (MCV-4) has been developed to provide T-cell dependent immune responses against 4 major disease-causing serogroups (A, C, Y, W-135). METHODS: In a comparative, randomized, modified double blind, controlled study in healthy 2- to 10-year-old U.S. children, safety and immunogenicity profiles of MCV-4 (n = 696) were compared with those of a licensed quadrivalent polysaccharide vaccine, Menomune A/C/Y/W-135 (PSV-4, n = 702). Vaccine-related adverse reactions were assessed for 28-day and 6-month follow-up periods. Serum bactericidal activity (SBA) was assayed in prevaccination, day 28 and 6-month postvaccination sera samples. RESULTS: Both vaccines were well-tolerated, with no vaccine-related serious adverse events and similar rates of mostly mild local and systemic reactions. Functional antibody (SBA) seroconversion percentages were significantly higher for all 4 serogroups in the MCV-4 group. The SBA geometric mean titers against serogroups A, C, Y and W-135 with MCV-4 were 1700, 354, 637 and 750, respectively, compared with PSV-4 (893, 231, 408 and 426) 28 days postvaccination (P < 0.001 for all comparisons). This significant difference persisted through 6 months. CONCLUSIONS: In 2- to 10-year-old children MCV-4 had a safety profile similar to that of PSV-4 and elicited significantly higher and more persistent serum bactericidal antibody responses against meningococcal serogroups A, C, Y and W-135 than did the licensed polysaccharide vaccine.

Evaluation of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children.

BACKGROUND: A quadrivalent measles, mumps, rubella and varicella vaccine would facilitate universal immunization against all 4 diseases, improve compliance and immunization rates and decrease the number of injections given to children and visits to physicians' offices. OBJECTIVES: To evaluate 1- and 2-dose regimens of a combined measles, mumps, rubella and varicella vaccine (ProQuad, referred to as MMRV) manufactured with a varicella component of increased potency. METHODS: In this partially blind, multicenter study, 480 healthy 12- to 23-month-old children were randomized to receive either MMRV and placebo or M-M-RII and VARIVAX. Injections were given concomitantly at separate sites. Subjects randomized to receive MMRV and placebo received a second dose of MMRV 90 days later. Subjects were followed for 42 days after each vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after each vaccination. RESULTS: Measles-like rash and fever during days 5-12 were more common after the first dose of MMRV (rash, 5.9%; fever, 27.7%) than after M-M-RII and VARIVAX (rash, 1.9%; fever, 18.7%). The incidence of other adverse events were similar between groups. Response rates were >90% to all vaccine components in both groups. Geometric mean titers to measles and mumps were significantly higher after 1 dose of MMRV than after administration of M-M-RII and VARIVAX. The second dose of MMRV elicited slight to moderate increases in measles, mumps and rubella antibody titers and a substantial increase in varicella antibody titer (from 13.0 to 588.1 glycoprotein antigen-based enzyme-linked immunosorbent assay units/mL). CONCLUSION: A 1- or 2-dose regimen of MMRV is generally well-tolerated when administered to 12- to 23-month-old children and has a safety and immunogenicity profile similar to that of M-M-RII and VARIVAX administered concomitantly.

Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults.

CONTEXT: Increasing reports of pertussis among US adolescents, adults, and their infant contacts have stimulated vaccine development for older age groups. OBJECTIVE: To assess the immunogenicity and reactogenicity of a tetanus-diphtheria 5-component (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3) acellular pertussis vaccine (Tdap) in adolescents and adults. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, modified double-blind, comparative trial was conducted in healthy adolescents and adults aged 11 through 64 years from August 2001 to August 2002 at 39 US clinical centers. INTERVENTIONS: A single 0.5-mL intramuscular dose of either Tdap or tetanus-diphtheria vaccine (Td). MAIN OUTCOME MEASURES: Antibody titers to diphtheria and tetanus toxoids for Tdap and Td were measured in sera collected from subsets of adolescents and adults, before and 28 days after vaccination. For pertussis antigens, titers in sera from Tdap vaccinees were assessed vs those from infants who received analogous pediatric diphtheria-tetanus-acellular pertussis vaccine (DTaP) in a previous efficacy trial. Safety was assessed via solicited local and systemic reactions for 14 days and adverse events for 6 months following vaccination. RESULTS: A total of 4480 participants were enrolled. For both Tdap and Td, more than 94% and nearly 100% of vaccinees had protective antibody concentrations of at least 0.1 IU/mL for diphtheria and tetanus, respectively. Geometric mean antibody titers to pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3 exceeded (by 2.1 to 5.4 times) levels in infants following immunization at 2, 4, and 6 months with DTaP. The incidence of solicited local and systemic reactions and adverse events was generally similar between the Tdap and Td groups. CONCLUSIONS: This Tdap vaccine elicited robust immune responses in adolescents and adults to pertussis, tetanus, and diphtheria antigens, while exhibiting an overall safety profile similar to that of a licensed Td vaccine. These data support the potential routine use of this Tdap vaccine in adolescents and adults.

Quadrivalent meningococcal (MenACWY-TT) conjugate vaccine or a fourth dose of H. influenzae-N. meningitidis C/Y conjugate vaccine (HibMenCY-TT) is immunogenic in toddlers who previously received three doses of HibMenCY-TT in infancy.

BACKGROUND: Immunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers. METHODS: Healthy infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine; or Hib-TT and DTaP-HBV-IPV (control). Recipients of HibMenCY-TT+DTaP-HBV-IPV were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months; MenACWY-TT co-administered with DTaP at 15-18 months; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months. Controls received DTaP only at 15-18 months due to Hib conjugate vaccine shortage. Serum bactericidal activity using human complement (hSBA) and safety were assessed one month after meningococcal vaccination. RESULTS: After vaccination with MenACWY-TT at 12-15 months or MenACWY-TT+DTaP at 15-18 months, all subjects previously primed for serogroups C/Y had hSBA ≥1:8 for these serogroups. At least 96.1% also had hSBA ≥1:8 for serogroups A/W. All subjects in the HibMenCY-TT group had hSBA ≥1:8 for serogroups C/Y. All pre-defined statistical criteria for meningococcal immunogenicity were satisfied. All vaccination regimens had acceptable safety profiles. CONCLUSION: Children primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y. These data provide support that MenACWY-TT, given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life. This study (110870/110871) is registered at www.clinicaltrials.gov NCT00614614.

Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™.

BACKGROUND: Co-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP) at age 15-18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers. METHODS: Infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15-18 months (Coad group); or HibMenCY-TT at 12-15 months and DTaP at 15-18 months (HibMenCY-TT group). Controls received DTaP at 15-18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination. RESULTS: Pre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone. CONCLUSION: Routine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the administration of a fourth DTaP dose following a 4-dose HibMenCY-TT vaccination series, or co-administered with MenACWY-TT in HibMenCY-TT-primed children.

Oral pleconaril treatment of picornavirus-associated viral respiratory illness in adults: efficacy and tolerability in phase II clinical trials.

We evaluated the efficacy and tolerability of oral pleconaril, an anti-picornavirus agent, in treating acute viral respiratory illness (VRI) in two double-blind, placebo-controlled trials. Otherwise healthy subjects, 14 years of age or older, who presented within 36 h of VRI symptom onset, were randomized to pleconaril 400 mg or matching placebo in liquid (first trial) or tablet (second trial) formulations twice-daily (first trial only) or three-times daily for 7 days. The infected subjects from the corresponding active and placebo groups (three-times daily dosing regimens) were combined for analysis. Among the subset of subjects with proven picornaviral infection in both studies (42% of total enrolled), pleconaril 400 mg three-times daily (n = 323) reduced the time to alleviation of illness (no rhinorrhoea and other symptoms mild or absent for > or = 48 h) compared with placebo (n = 264) (median: 10.0 days for placebo and 8.5 days for pleconaril; P = 0.029). In addition, pleconaril reduced the time to a > or = 50% reduction from baseline in total symptom severity score (median: 4.5 days for placebo and 3.5 days for pleconaril; P = 0.038). Significant reductions in the number of tissues used for nose-blowing (20% reduction) and in nights of disturbed sleep (16% reduction) were also observed. Pleconaril was generally well tolerated; the liquid formulation caused gastrointestinal disturbance in all groups (diarrhoea 10-14%, nausea 5-9%, abdominal discomfort 6-8%), and tablets were associated with a greater incidence of nausea (3% for placebo versus 7% for pleconaril, P = 0.003). Pleconaril 400 mg administered three-times daily reduced the duration and severity of picornaviral VRI in adolescents and adults.

Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination.

OBJECTIVES: To assess the impact of a birth dose of hepatitis B vaccine (HepB) on the reactogenicity and immunogenicity of a novel diphtheria-tetanus-acellular pertussis (DTaP)- HepB-inactivated poliovirus (IPV)/ type b (Hib) combination vaccine administered subsequently at 2, 4 and 6 months of age. METHODS: Neonates ( = 550) were randomized into two groups with regard to receipt of HepB at birth. All subjects in both groups received DTaP-HepB-IPV/Hib at 2, 4 and 6 months of age. Solicited local and general adverse events were recorded for 8 days after each dose. Antibodies to hepatitis B surface antigen were measured 1 month after the third dose of DTaP-HepB-IPV/Hib in a subset of 170 infants; titers of at least 10 mIU/ml were considered protective. RESULTS: The DTaP-HepB-IPV/Hib combination vaccine was well-tolerated in both groups. Of the infants who received a birth dose of HepB, 22.6% had severe (Grade 3) reactions after any of the three doses of DTaP-HepB-IPV/Hib combination vaccine compared with 23.2% of subjects who did not receive a birth dose of HepB (difference, -0.5%; 90% confidence interval, -7.4 to 6.1). Antibody to hepatitis B surface antigen titers were > or =10 mIU/ml for all tested infants. Geometric mean titers were 2996.2 and 1240.1 mIU/ml with and without a birth dose of HepB, respectively. CONCLUSIONS: A HepB birth dose does not increase the reactogenicity of a combination DTaP-HepB-IPV/Hib vaccine administered at 2, 4 and 6 months of age, and all tested subjects achieved protective anti-HBs titers (> or =10 mIU/ml), although geometric mean titers were higher when a birth dose of HepB was given.

The health-related quality of life effects of once-daily cetirizine HCl syrup in children with seasonal allergic rhinitis.

Seasonal allergic rhinitis (SAR) can adversely impact children's physical, psychological, and social functioning and well-being, that is, their health-related quality of life (HRQL). This study assessed HRQL in children 6 to 11 years treated with cetirizine HCl syrup, while concurrently assessing symptomatic relief and safety. In an open-label, non-comparative study, 544 children from 124 centers in the United States were instructed to take cetirizine HCl syrup (10 cc of 1 mg/mL) each evening for 4 weeks. Children experienced statistically significant improvements in HRQL with significant reductions in mean symptom score (p < 0.001) during the treatment period. Results were consistent across age groups (6-7, 8-9, 10-11 years). These results suggest that the symptomatic relief and tolerability profile of cetirizine HC1 syrup daily translates into improvements in the HRQL of children with SAR. This 4-week open label study is among the first to evaluate the effect of antihistamine treatment on HRQL outcomes in children.

Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: end-of-study analysis of a Phase III randomized trial.

The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received ≥1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection.