In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising.

We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine, which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine (DTP) with Hib (PRP-OMPC) and hepatitis B vaccine (HB), in a series of three studies involving 2156 infants. The vaccination schedule was 2, 4, 6 and 18 months for all studies. In addition, subjects in the third study also received a dose of monovalent hepatitis B vaccine at birth. The principal study was a randomised double blind trial of two separate, but concurrently administered vaccines in each of three groups: pentavalent vaccine [DTP-Hib-HB] plus placebo (Group A, n=619); quadrivalent vaccine [DTP-HB] plus Hib vaccine (Group B, n=620); and bivalent vaccine [Hib-HB] plus DTP (Group C, n=226). The second study (Group D, n=231) was an open trial of three separate, but concurrently administered licensed control vaccines (DTP, Hib and HB). The third study (Group E, n=460) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations, and a month after the 6- and 18-month vaccinations. A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination. The pentavalent vaccine, whether or not preceded by a birth dose of hepatitis B vaccine, was generally well tolerated at all administration times, and had a reactogenicity profile similar to that observed for licensed vaccine controls. Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups. The anti-HBs responses (% > or = 10 mIU/ml) following the 6-month dose of vaccines were, respectively, for Groups

A-E:

83.2, 91.7, 96.5, 98.8 and 93.9%, and following the 18-month doses: 87.9, 97.5, 98.8, 98.8 and 92.8%. Anti-PRP responses (% > or = 1.0 microg/ml) following the 6-month dose for Groups A-D were 86.0, 90.5, 91.2, and 74.4%, and after the 18-month dose for Groups A-E were 97.3, 98.3, 98.1, 97.0, and 99.5%. Consistently higher geometric mean titres (GMTs) for pertussis antibodies to agglutinogens (Agg2, Agg3) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine, though they were somewhat lower for pertussigen (PT). Except for the hepatitis B response, antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate, but concurrently administered licensed control vaccines. A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2, 4, 6 and 18 months was not countered by any clinically significant decrease in seroresponses.

BACKGROUND:

Combination vaccines are urgently needed to reduce the number of injections given to young children. The aim of the study was to evaluate the safety and immunogenicity of a combination vaccine that contains diphtheria and tetanus toxoids and acellular pertussis antigens (DTaP), recombinant hepatitis B surface antigen (HepB) and Haemophilus influenzae type b (Hib) polysaccharide conjugated to tetanus toxoid (PRP-T).

METHODS:

Four hundred five infants were randomized equally to three groups and immunized at 2, 4 and 6 months of age with: (1) DTaP/HepB vaccine used to reconstitute lyophilized PRP-T vaccine and administered as a single injection; (2) DTaP/HepB vaccine and PRP-T vaccine administered as two separate injections; or (3) DTaP, HepB and PRP-T vaccines administered as three separate injections. Safety was closely monitored, and blood specimens were obtained to assess antibody responses to each vaccine antigen.

RESULTS:

All study vaccines were well-tolerated, and the rates of systemic and injection site reactions were similar between groups. After the third dose the geometric mean antibody concentrations to Hib were significantly lower in subjects in Group 1 (1.63 microg/ml) compared with subjects in Groups 2 and 3 (6.26 and 6.15 microg/ml, respectively; P < 0.0001). Subjects with antibody concentrations <1.0 microg/ml after the third dose responded well to a booster dose of Hib conjugate vaccine given at 11 to 15 months of age (41 of 44 with anti-PRP > or = 1.0 microg/ml). Differences between groups for antibody responses to the other vaccine components were not clinically significant.

CONCLUSIONS:

Infants given a combined DTaP/ HepB/PRP-T vaccine experienced a significantly lower antibody response to the PRP-T component than infants given PRP-T vaccine as a separate injection. However, the immune response to a booster dose of Hib conjugate vaccine indicated the presence of immunologic memory.

The results of the following studies are reported: a longitudinal double blind trial comparing Lederle-Takeda APDT vaccine with Lederle DTP vaccine in two, four and six month old infants; two double blind similar APDT vs DTP trials in 18 month old and four to six year old children; a large longitudinal open trial with APDT in two, four and six month old infants and a household contact efficacy trial with Takeda APDT in Japan. APDT vaccine recipients had a lesser frequency and less severe reactions than whole cell vaccine recipients. Antibody responses to lymphocytosis-promoting factor and agglutinogens were higher in DTP recipients; APDT recipients had a better serologic response to filamentous hemagglutinin. Equivalent 69K protein antibody responses were seen. Vaccine efficacy in the household contact study was 98% (95% CI = 84% to 99%) against classical pertussis and 81% (95 CI = 64% to 90%) if all respiratory illnesses are considered.

This study was conducted to determine the immunogenicity and safety of a 7-valent CRM197 protein conjugated pneumococcal vaccine (PCV7) in Korean infants immunized at 2, 4 and 6 months. A total of 202 infants were enrolled and 146 and 141 infants were, respectively, included in post-2nd dose and post-3rd dose immunogenicity evaluations conducted on a per protocol basis. After two and three PCV7 vaccinations, 63.0-98.0 and 97.2-100% of infants achieved an antibody level of >or=0.35microg/mL, respectively, with a lowest against serotype 6B. No vaccination-related serious adverse reactions were observed. Thus, PCV7 appears safe and highly immunogenic in Korean infants, and adopting two doses for a primary series could be a feasible option for facilitating vaccine coverage rate.

In preparation for a large efficacy trial in Germany, a pilot study was initiated in December 1990. In this study 149 infants were enrolled; with double-blind randomization 75 received Lederle/Takeda acellular pertussis component diphtheria-tetanus-pertussis vaccine (APDT) and 74 received Lederle whole-cell pertussis component diphtheria-tetanus-pertussis vaccine (DTP). The mean age at first dose was 3.5 months, and the second and third doses followed at 6-week intervals. Reactions were relatively mild with both vaccines; in general they were less frequent following APDT. The IgG antibody responses to lymphocytosis promoting factor (LPF) and fimbriae-2 were similar in both groups whereas the responses to pertactin and filamentous haemagglutinin (FHA) were greater in APDT recipients. DTP recipients had greater responses to tetanus and diphtheria toxoids. When age of first dose was examined (8-12 weeks versus 16-20 weeks), it was found that young age had a suppressive effect on antibody responses in DTP but not APDT recipients to LPF toxoid, pertactin, fimbriae-2, and tetanus and diphtheria toxoids. High values of transplacentally acquired antibody lessened the response to LPF toxoid and tetanus toxoid in DTP recipients and to tetanus toxoid in APDT vaccinees. The IgG immune response to LPF toxoid, FHA and fimbriae-2 was found to be more uniform in APDT recipients than in DTP vaccinees. An IgA antibody response to fimbriae-2 was noted in 13% of DTP recipients but in no APDT vaccinees. The broad immunogenicity and mild reactogenicity of this APDT vaccine justifies its use in the German efficacy trial.

We compared antibody levels following separate but simultaneous administration of diphtheria and tetanus toxoids with acellular pertussis vaccine (DTaP) containing pertussis toxoid, filamentous hemagglutinin, and pertactin (PRN); hepatitis B vaccine; and Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate; PRP) vaccine conjugated to tetanus toxoid (PRP-T) with those following administration of a combination of a DTaP-hepatitis B vaccine-PRP-T to infants at 2, 4, and 6 months of age. The antibody response to a booster dose of PRP conjugate vaccine (CRM197-OS) in infants with low (< 1 microgram/mL) or undetectable (< 0.10 microgram/mL) postpriming levels of antibody to PRP was also studied. Antibody levels were quantitated before and after dose 3 by enzyme-linked immunosorbent assay, radioimmunoassay, or neutralization assay. Seroresponse rates were not different between the two vaccine groups except for rates of response to PRP. There was a trend that levels of antibody to all the antigens included in the combination vaccine were lower than those of antibody to antigens in separate vaccines; for levels of antibody to diphtheria toxoid (P = .001), PRN (P < .0001), and PRP (P < .0001), the differences were significant. Despite low or undetectable postpriming levels of antibody to PRP, high-titered (geometric mean concentration, 9.02 micrograms/mL; range, 1.0-81.5 micrograms/mL), immunoglobulin G-predominant antibody to PRP was produced following a booster dose of CRM197-OS, a finding consistent with a memory response.

Se evaluó el uso de la tecnología de Flujo de Filtración Tangencial (FFT), para obtener la toxina diftérica a partir de cultivos de la bacteria Corynebacterium diphtheriae, usando el proceso de Microfiltración (MF), para eliminar el paquete celular y posteriormente, a partir del filtrado obtenido, concentrar y diafiltrar la toxina diftérica usando el proceso de Ultrafiltración (UF). Se determinaron características de los filtros, condiciones de trabajo y dimensionamiento de los equipos a adquirir para la producción industrial de Toxina Diftérica. Se evaluaron el flujo, tiempo, rendimiento del proceso y las características del producto obtenido, utilizando cultivos con Toxina Diftérica en un equipo de filtración de laboratorio, diseñado para producir el efecto de FFT. Seseleccionó las membranas tipo cassettes, formato Médium Screen, porosidad 0,2 μm, como las adecuadas para el proceso de MF, ya que mostraron 100% de transmisión de la Toxina Diftérica, ausencia de restos celulares y flujo promedio de filtrado de 9.16 L/m2h. Así mismo, se seleccionaron las membranas tipo cassettes, formato Omega, porosidad 10 y 30 kDa, como las adecuadas para el proceso de UF, ya que mostraron 100% de recuperación de la toxina, ausencia de toxina en el filtrado y adecuados flujos de filtrado (97,5 y 125,9 L/m2h, respectivamente), Estos resultaron permitieron dimensionar, considerando las variables a utilizar en la producción industrial (Volumen 650 a 950 Litros, Tiempo de Procesos, 3 a 5 horas), el área de filtración de los equipos de MF y UF a adquirir, estimados en 20m2 y 5m2, respectivamente.

BACKGROUND:

Infants are often subjected to painful procedures such as diphtheria, pertussis, tetanus (DTP) immunization. Despite its negative effects, pain in infants has not got enough attention. Sweet oral solution has analgesic effect.
Objective To determine whether oral sugar solution can reduce the duration of crying in infants who got DTP immunization.

METHODS:

This was a randomized, double-blind controlled trial performed at Growth and Development Clinic of Dr. Sardjito
General Hospital and two Primary Health Centers in Yogyakarta. Study subjects were 4-6 month-old infants who got the 3rd DTP immunization. Subjects were randomly allocated to receive 2 ml 75% oral sugar solution (intervention group) or 2 ml drinking water (placebo) just before the immunization. Crying was recorded from just before the injection until 3 minutes after.

RESULTS:

Eighty-six subjects were enrolled; 42 subjects received sugar solution and 44 subjects received placebo. Sugar solution reduced the median duration of first cry about 38 seconds or 32% (P=0.03) and reduced the median duration of total crying about 35 seconds or 24% (P=0.02).

CONCLUSION:

Administration of 2 ml 75% oral sugar solution can alleviate pain associated with DTP immunization as shown by reduced duration of crying.

INTRODUCTION:

In recent years, acellular pertussis combination vaccines have facilitated compliance with and coverage of the national immunisation programme in Singapore. This phase-II study (Rota-007) evaluated the immunogenicity, reactogenicity and safety of a DTPa-IPV/Hib combined vaccine when co-administered with a rotavirus vaccine.

MATERIALS AND METHODS:

A total of 2464 children aged 3 months were vaccinated with DTPa-IPV/Hib together with a randomised 1:3 ratio of either placebo (n=653) or 1 of 3 different formulations of a rotavirus vaccine. Blood samples were collected for immunogenicity analysis 1 month after the third DTPa-IPV/Hib vaccine dose in a subset of subjects (n = 640). Local and general reactogenicity and unsolicited adverse events were recorded during the follow-up after each vaccination.

RESULTS:

Serological analysis showed >95% response for all antigens in the co-administered DTPa-IPV/Hib vaccine, with no difference between the rotavirus vaccine and placebo groups. No differences in adverse events and reactogenicity were reported in the rotavirus vaccine and placebo groups. Only 0.2% of the subjects reported Grade 3 adverse events. Three subjects (from the vaccine groups) died during the study, which were assessed by the investigators as unrelated to vaccination. No deaths were reported in the placebo group.

CONCLUSION:

The combined DTPa- IPV/Hib vaccine is safe, well tolerated and highly immunogenic when given alone or coadministered with the rotavirus vaccine for infants in Singapore.