Immunologic response to Hib tetanus toxoid conjugated vaccine coadministered with DTPa either mixed or in two separate injections in toddlers not primed with Hib vaccine.

This open randomized study compared the immunogenicity and safety of a diphtheria-tetanus-acellular pertussis (DTPa) and H. influenzae polyribosylribitol phosphate conjugated to the tetanus toxoid (Hib-PRP-T) vaccine (mixed prior to administration) with separate injections of DTPa and Hib vaccines in toddlers aged two years. A total of 119 children (60 mixed; 59 separate administration), primed with DTPw, but not with Hib vaccine were enrolled. Prior to immunization only 10.3% of toddlers had anti-PRP antibody titres > or =1.0 microg/ml, compared with all children on Days 7 and 30. The anti-PRP and anti-tetanus antibody geometric mean concentrations were lower after the combined DTPa/Hib vaccine compared to separately administered vaccines (47.16 microg/ml vs 78.36 microg/ml and 24.95 IU/ml vs 40.63 IU/ml, respectively). One month after vaccination all children had anti-tetanus and anti-diphtheria antibody titres above the protective level of > or =0.1 IU/ml. The rates of recorded adverse events were similar and mostly mild or moderate in intensity whether the vaccines were combined as a single injection or given separately. We conclude that in 2-year old children, previously not immunized against Hib, a single dose of DTPa and Hib was safe and highly immunogenic irrespective of whether it was given as a combined vaccine or separate injections. Although the increase in anti-T and early (7-10 days after) anti-PRP concentrations was greater when the vaccine components were given separately than after combined administration, the DTPa/Hib combined vaccine would provide an effective method of delivering primary Hib vaccination in unprimed toddlers.

Safety and immunogenicity of a primary course and booster dose of a combined diphtheria, tetanus, acellular pertussis, hepatitis B and inactivated poliovirus vaccine.

Primary immunization at 3, 4.5, and 6 months and boosting between 15 and 27 months of age with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) vaccine was compared with separate administration of DTPa-HBV and IPV to healthy children (trials DTPa-HBV-IPV-019/033). Antibody titres were measured before and 1 month after primary and booster courses. Solicited local and general symptoms were recorded using diary cards. One month after primary vaccination, all children in both groups developed antibody titres above the assay cut-off for all vaccine components. Significantly higher anti-diphtheria, anti-pertactin (PRN) and anti-polio GMTs were measured following DTPa-HBV-IPV than DTPa-HBV plus IPV. Prior to boosting similar seroprotection/seropositivity rates were recorded in both groups. After boosting all children had seroprotective levels of diphtheria, tetanus, polio and HBV. Criteria for pertussis vaccine response were fulfilled in most children. Significantly higher anti-PRN GMTs were measured following DTPa-HBV-IPV than DTPa-HBV plus IPV. There was no difference between groups in the incidence or intensity of local and general symptoms after primary or booster vaccination, except for fever which was more frequent after the booster dose in the combined vaccine group. Both vaccine regimens were well tolerated and immunogenic, however the combined administration has the advantage of being administered as a single injection.

Pertussis outbreak in a basic school in Estonia: description, contributing factors and vaccine effectiveness.

The aim of the current study was to assess the epidemiological situation concerning the emergence of a pertussis outbreak, as well as potential contributing factors and vaccine effectiveness. A retrospective epidemiological description and an analysis of the outbreak among students were performed. The basic school in Adavere had a total of 150 students in 2003. Of these, 54 cases of pertussis, with median age 12 y, all corresponding to clinical case definition, were identified with an attack rate of 36%. Regarding confirmation of the diagnosis, out of all clinical cases, 18 were confirmed by laboratory testing (2 by isolation of B. pertussis and 16 serologically based on single sera) and 36 with epidemiological linkage only. Of all the students with pertussis, 35 (65%) had received 4 doses and 6 (11%) 3 doses of DTwP vaccine; 13 (24%) students had received fewer than 3 doses or were unvaccinated. The contributing factors in generating this outbreak were close epidemiological contacts, late identification of pertussis diagnosis in the primary, secondary and later cases, as well as a too late initiated active surveillance. In this outbreak, low vaccine effectiveness and low vaccination coverage also played an important role.

Double-blind study comparing the immunogenicity of a licensed DTwPHib-CRM197 conjugate vaccine (Quattvaxem) with three investigational, liquid formulations using lower doses of Hib-CRM197 conjugate.

We performed a double-blind clinical study to evaluate the safety and immunogenicity of four formulations of a DTwPHib full liquid vaccine, three of which contained fractional doses of the 10 microg-dose of CRM197-Hib conjugate vaccine. A total of 261 infants were enrolled and randomised to receive at 3, 4 and 5 months of age, in a double-blind fashion, one of the four DTwPHib vaccine formulations containing 10, 5, 2.5 or 1.25 microg of CRM197-Hib conjugate. Post-immunization reactions were similar in the four vaccine groups, they were mild, transient and resolved without sequelae. The seroconversion rates to anti-PRP titres > or = 0.15 microg/mL were 100%, 98%, 97% and 98% in the groups 10, 5, 2.5 and 1.25 microg, respectively. The seroconversion rates to anti-PRP titres > or =1 microg/mL were 95%, 97%, 88% and 90%, again respectively. Anti-PRP GMTs were 18, 17, 7.82 and 6.94 microg/mL, respectively. All subjects were protected against tetanus and diphtheria, and >80% seroconverted to pertussis. High, and similar, levels of anti-PRP GMTs were elicited by the formulations with 10 and 5 microg of CRM197-Hib conjugate. Although the formulations with 2.5 and 1.25 microg of CRM197-Hib elicited lower levels of anti-PRP GMTs, they were immunogenic and are possible candidates for further development.