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Safety and immunogenicity of six acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fifth dose in four- to six-year-old children.

OBJECTIVE: To evaluate the safety and immunogenicity of 6 different acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) and with 1 licensed whole-cell pertussis vaccine (DTwP) as a fifth dose in children who had previously received the same DTaP, a different DTaP, or DTwP as primary and fourth-dose vaccinations. METHODS: Healthy 4- to 6-year-old children were enrolled at 5 National Institute of Allergy and Infectious Diseases Vaccine Treatment and Evaluation Units to receive a fifth dose of a DTaP or DTwP vaccine. All had been randomly assigned to receive 3 primary doses of DTaP or DTwP at 2, 4, and 6 months and a fourth-dose booster at 15 to 20 months of age as part of earlier National Institutes of Health multicenter acellular pertussis vaccine trials. Parents recorded the occurrence and magnitude of fever, irritability, and injection site redness, swelling, and pain for 3 days after vaccination. Sera obtained before and 1 month after the booster vaccination were analyzed by enzyme-linked immunosorbent assay for antibody to pertussis toxin, filamentous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxoid. Safety and/or immunogenicity data are reported for 317 children who received DTaP and 10 children who received DTwP. RESULTS: Fever and moderate or severe irritability were uncommon following the fifth dose of DTaP vaccine and were generally less frequent than following the fourth dose. However, for the DTaP vaccine groups, redness, swelling, and pain increased in prevalence compared with the fourth dose. The time course and frequency of reactions following DTaP vaccination were generally similar in children who received the same DTaP, a different DTaP, or DTwP for previous doses in the 5- dose series. No significant differences among the DTaP vaccines were detected in the occurrence of reactions, but the statistical power to detect differences was limited by sample size. Significant increases in antibodies directed against the included antigens were observed for all DTaP vaccines in paired pre- and post-fifth dose sera. Post-fifth dose antibody concentrations differed significantly among the DTaP vaccines. Some children in the study showed an antibody response to an antigen not reported to be in the DTaP vaccine. CONCLUSION: All the studied DTaP vaccines performed similarly with regard to reactions, whether given as a fifth sequential dose of the same vaccine, a mix of different DTaP vaccines in the 5-dose sequence, or after 3 DTwP and 1 DTaP vaccinations. Large injection site reactions occurred more frequently after the fifth dose of DTaP than after the previous 4 doses. A fifth dose of all DTaP vaccines induced an antibody response to those antigens contained in the vaccine. No DTaP was consistently most or least reactogenic or immunogenic.

Antibodies, Bacterial↗

Six-component vaccines: new preparations. Simpler hepatitis B vaccination of infants.

(1) Two six-component vaccines available in France (Hexavac and InfanrixHexa) are designed for primary and booster vaccination of infants. A single intramuscular injection delivers a five-component vaccine (diphtheria, tetanus, poliomyelitis, Haemophilus influenzae type b and acellular pertussis) and a hepatitis B vaccine. (2) The clinical evaluation dossier on InfanrixHexa includes four trials versus separate injections of a five-component vaccine and a hepatitis B vaccine at two distinct sites. (3) For primary vaccination, no difference in immunogenicity was found between InfanrixHexa and separate vaccination for 5 of the 6 components. The serological response to Haemophilus was weaker with InfanrixHexa, but whether or not this translates into worse long-term clinical protection is unknown. (4) After primary vaccination, major adverse events were a little rarer with InfanrixHexa than with separate vaccination. There was no difference in adverse events between InfanrixHexa and separate vaccination after the recommended booster between the ages of 16 and 18 months. (5) Evaluation data on Hexavac published by Aventis Pasteur MSD are very limited. We found only one trial in the primary vaccination setting, versus vaccination at two distinct sites with a five-component vaccine and a hepatitis B vaccine. (6) The serological response to hepatitis B virus and Haemophilus was significantly weaker with Hexavac than with separate vaccination, but no difference was found regarding the other four components. It is not known if this difference has any clinical implications. There was no difference in adverse events between Hexavac and separate vaccination. (7) The vaccination schedule depends on whether or not separate hepatitis B vaccine is required at birth. A six-component vaccine and a five-component vaccine can be used alternately.

Diphtheria↗

Virological protection of sows upon challenge with Aujeszky's disease virus after multiple vaccinations with attenuated or inactivated vaccines.

The frequency with which sows are vaccinated during eradication programmes has been determined rather arbitrarily in the past, without the necessary scientific support. In the present study the efficacy of repeated vaccinations against Aujeszky's disease virus (ADV) with two inactivated vaccines and with one attenuated ADV-strain (Bartha) suspended in either oil-in-water or saline was evaluated in 40 breeding sows originating from five farms by the assessment of the clinical and virological protection upon an experimental challenge. Sows with two different histories of number of booster vaccinations after a base immunization were selected: young sows which had received 1-3 booster vaccinations and old sows which had received 8-10 booster vaccinations. Two seronegative and two gE-positive sows were included as controls. After challenge, clinical signs such as anorexia and fever were observed in the two seronegative sows and only in four out of the 18 sows which had repeatedly been vaccinated with inactivated vaccines. The mean duration of virus excretion significantly differed (P < 0.05) between the experimental groups. In seronegative sows, virus shedding lasted for 12.5 days. This period was reduced to 6.8-7.9 days in the groups of sows vaccinated with inactivated vaccines having no effect by the number of booster vaccinations and type of vaccine. In the groups of sows vaccinated with Bartha vaccine, challenge virus was detected during 3.7-5.3 days when revaccinated 1-3 times. A reduction to 0.7-1.2 days was obtained with a higher number of boosters (8-10) but only when the vaccine virus was suspended in o/w. Considering the mean cumulative values of virus excretion (area under the curve) it can be stated that sows frequently vaccinated with inactivated vaccines excrete significantly (P < 0.05) higher amounts of virus (26.0-31.5) than sows frequently vaccinated with attenuated ones (1.6-23.7). We may conclude from the present data that the attenuated vaccine virus Bartha, especially when suspended in o/w is superior to inactivated vaccines for inducing clinical and virological protection of sows in the field during their whole breeding period.

Animals↗

Role of whole-cell pertussis vaccine in severe local reactions to the preschool (fifth) dose of diphtheria-pertussis-tetanus vaccine.

OBJECTIVE: To estimate the contribution of whole-cell pertussis vaccine to severe local reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine. DESIGN: Double-blind randomized controlled trial. SETTING: Urban community. PARTICIPANTS: Volunteer sample of 200 healthy children 4 to 6 years old who were eligible for the fifth dose of DPT vaccine. INTERVENTIONS: Children received, in both arms, either diphtheria toxoid-tetanus toxoid (DT) and monovalent pertussis vaccines (group A, 99 children) or DPT and meningococcal vaccines (group B, 101 children). All were licensed products from single lots. The children were assessed 24 hours later by a trained observer. Serum samples obtained before vaccination were tested for antibodies to tetanus and diphtheria toxins and five pertussis antigens by means of enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of severe local reactions (an area of redness or swelling or both of 50 mm or greater) 24 hours after vaccination. Relation between serum antibody levels before vaccination and rates of severe local reactions to corresponding vaccines. RESULTS: All of the subjects were followed up 24 hours after vaccination. Severe redness was present in 38% given DPT vaccine, 29% given intramuscular pertussis vaccine and 9% given DT vaccine (p < or = 0.002, three-way comparison). Severe swelling was common after vaccination with all three products. After intramuscular pertussis vaccination a relation was evident between the prevaccination levels of antibody to whole-cell pertussis bacteria and the rates of redness (p < 0.02) but not between the prevaccination subcellular antibody levels and the rates of redness. CONCLUSION: That pertussis vaccine resembled the DPT vaccine in causing severe redness suggests that it is the principal cause of such reactions after DPT vaccination. The DT vaccine was also reactogenic; thus, cumulative sensitization to one or more of its constituents may be a factor.

Antibodies, Bacterial↗

Association between administration of hepatitis B vaccine at birth and completion of the hepatitis B and 4:3:1:3 vaccine series.

CONTEXT: The association between infant age at initiation of hepatitis B vaccination and completion of the 3-dose hepatitis B vaccination series is unclear. OBJECTIVE: To assess the association between administration of the first dose of hepatitis B vaccine within 7 days of birth and completion of the hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles-containing vaccine, and 3 doses of Haemophilus influenzae type b vaccine). DESIGN, SETTING, AND PARTICIPANTS: Analysis of data from the 1998 National Immunization Survey, a random-digit-dialing telephone survey (n = 34,480 completed interviews) of parents of children aged 19 to 35 months from 50 states and 28 selected urban areas in the United States that included a provider record check mail survey. MAIN OUTCOME MEASURES: Percentage of infants who received at least 3 doses of hepatitis B vaccine and percentage who received the 4:3:1:3 vaccine series, by age at receipt of the first dose of hepatitis B vaccine. RESULTS: Overall, 86.9% of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis B vaccine, and 79.9% completed the 4:3:1:3 vaccine series. Multivariate analysis indicated that, compared with children who received the first hepatitis B vaccine dose within 7 days of birth, odds ratios (ORs) for not completing the 3-dose hepatitis B vaccine series among children who received the first dose at 8 to 41 days, 42 to 91 days, 92 to 182 days, 183 to 273 days, and 274 or more days of age were 2.4 (95% confidence interval [CI], 2.0-3.0), 7.8 (95% CI, 6.5-9.3), 9.6 (95% CI, 7.0-13. 3), 18.3 (95% CI, 12.0-28.0), and 46.6 (95% CI, 33.7-64.5), respectively; ORs for not completing the 4:3:1:3 vaccine series among these same groups were 1.0 (95% CI, 0.8-1.1), 1.0 (95% CI, 0. 8-1.1), 1.7 (95% CI, 1.3-2.3), 3.8 (95% CI, 2.6-5.6), and 4.0 (95% CI, 2.9-5.5), respectively. CONCLUSION: Administration of the first dose of hepatitis B vaccine at birth is associated with increased likelihood of completion of the hepatitis B vaccination series. JAMA. 2000;284:978-983

Child, Preschool↗

Poor health care worker vaccination coverage and knowledge of vaccination recommendations in a tertiary Australia hospital.

OBJECTIVES: Guidelines for vaccination of health care workers (HCWs) have been available in Victoria since 1998. We estimated knowledge and attitudes towards vaccination among HCWs as well as self-reported vaccination status in a tertiary adult hospital in Melbourne, Australia. METHODS: A cross-sectional survey was conducted in July 2000 using a telephone questionnaire and proportionate random sampling. RESULTS: Only 18% of 269 HCWs were fully vaccinated. Most (76%) had not heard of or seen current guidelines for HCW vaccination despite a stated belief in the importance of full vaccination (94%) and a willingness to update their vaccination status if necessary (96%). Less than half kept vaccination records (39%). Hepatitis B vaccination (95%) was most commonly completed. However, only half of all HCWs had received influenza vaccination in the past 12 months and other vaccines often had suboptimal coverage. A common reason cited for avoiding vaccination was concern over vaccine side effects (17%). While the hospital staff clinic was an acceptable site for vaccination, improved access was seen as important. CONCLUSIONS: HCW vaccination coverage and knowledge of vaccination requirements were poor. Concerns about vaccine side effects were common. IMPLICATIONS: Adequately resourced HCW vaccination programs that include ongoing education for HCWs and improved access to vaccination are necessary to improve vaccination coverage and reduce the risk of vaccine-preventable diseases among staff and patients.

Attitude of Health Personnel↗

Intratumoral vaccination and diversified subcutaneous/ intratumoral vaccination with recombinant poxviruses encoding a tumor antigen and multiple costimulatory molecules.

PURPOSE: Intratumoral (i.t.) vaccination represents a potential modality for the therapy of tumors. Previous i.t. vaccination studies have focused on the efficacy of i.t. vaccination alone. There are no reports that clearly compared i.t. vaccination with systemic vaccination achieved by s.c., intradermal, or i.m. injection, or combining both modalities of systemic and i.t. vaccination. Here, we compared the antitumor effects induced by a systemic vaccination regimen (s.c.) and i.t. vaccination, and a sequential s.c/i.t. vaccination regimen. In this study, we used a recombinant vaccinia virus containing the transgenes for carcinoembryonic antigen (CEA) and a triad of T-cell costimulatory molecules (B7-1, ICAM-1, and LFA-3; designated rV-CEA/TRICOM) for s.c. priming and a replication defective avipox (fowlpox) virus containing the same four transgenes (designated rF-CEA/TRICOM) for i.t. vaccination or s.c. booster vaccinations. EXPERIMENTAL DESIGN: Vaccination was started on day 8 after s.c. implantation with CEA-positive tumors. We compared the antitumor activity induced by these vaccines when administered via the i.t. route versus the s.c. route. Subsequent therapy studies examined the sequential combination of these routes, s.c. priming with rV-CEA/TRICOM followed by i.t. boosting with rF-CEA/TRICOM. Initial studies were conducted in conventional mice to define optimal vaccine regimens and then in CEA-transgenic mice that expressed CEA as a "self" antigen in a manner similar to that of an advanced colorectal cancer patient. RESULTS: The results demonstrate that the antitumor activity induced by i.t. vaccination is superior to that induced by s.c. vaccination. For more advanced tumors, a s.c. priming vaccination, followed by i.t. boosting vaccinations was superior to either s.c. or i.t. vaccination alone. Both of these phenomena were observed in tumor models where the tumor-associated antigen is a foreign antigen and in a CEA-transgenic tumor model where the tumor-associated antigen is a self-antigen. The cytokine, granulocyte macrophage colony-stimulating factor admixed in vaccines, was shown to be essential in inducing the antitumor activity. CONCLUSIONS: These studies demonstrate that the diversified vaccine regimens that consisted of s.c. prime and i.t. boosts with CEA/TRICOM vectors could induce antitumor therapy superior to that seen by either route alone.

Animals↗