Influenzae Type-b Conjugate Research Articles

Safety profile of Infanrix hexa – 17 years of GSK’s passive post-marketing surveillance

ABSTRACT Introduction This paper reports 17 years of passive safety surveillance of routine use of the pediatric hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b-conjugate vaccine (DTPa-HBV-IPV/Hib, Infanrix hexa, GSK). Methods Global post-licensure passive surveillance data collected in GSK’s central safety database since DTPa-HBV-IPV/Hib’s launch (2000) are described. Results The most common spontaneously reported adverse events (AEs) after DTPa-HBV-IPV/Hib vaccination in children were fever (reporting rate: 7.74/100,000 doses distributed), crying (2.62/100,000), injection site erythema (1.87/100,000) and swelling (1.28/100,000). A review of extensive limb swelling did not reveal any safety concerns. An observed-to-expected analysis did not show an increased risk of sudden death after DTPa-HBV-IPV/Hib vaccination, in line with previous observations. The analyses confirmed that increases in spontaneous reporting proportions of convulsions with/without fever and hypotonic-hyporesponsive episodes after co-administration of DTPa-HBV-IPV/Hib and 13-valent pneumococcal conjugate vaccine remained small and their clinical significance unknown. The most common vaccination errors were mistakes in the vaccination schedule. Reporting of preparation errors (mostly reconstitution) was low and did not impact the vaccine’s benefit-risk profile. Conclusions Seventeen years of post-licensure experience confirm confidence in the safety profile of DTPa-HBV-IPV/Hib in routine use, with a favorable benefit-risk profile in infants and toddlers.

Antibody response to Haemophilus influenzae type-b conjugate vaccine in children and young adults with congenital asplenia or after undergoing splenectomy

Absence of the spleen constitutes a risk of infection caused by encapsulated bacteria. The aim of our study was to determine the immune response to Haemophilus influenzae type-b (Hib) conjugate vaccine (HibCV) in asplenic individuals, considering the cause of asplenia, the age when splenectomy was carried out, and previous Hib vaccinations. Twenty asplenic patients, aged five to 25 years, were immunized with a single dose of HibCV. The specific antibody concentrations against HibCV were measured by enzyme-linked immunosorbent assay. Before vaccinations, the geometric mean antibody concentration (GMC) had an average value of 3.21 μg/ml and was comparable for all of the patients, regardless of the causes of asplenia. After vaccinations, the GMC was significantly higher, with an average of 6.78 μg/ml. Further, 4.5 years after vaccinations, the GMC was comparable to that of previously unvaccinated children. Moreover, 17/20 patients had GMC ≥ 1.0 μg/ml, which included all of the children with congenital asplenia, children splenectomized before the age of six years, and only 57% of children splenectomized after that age. HibCV gives asplenic patients long-term protection. Hence, HibCV should be administered regardless of previous vaccinations and time from splenectomy, even if antibody evaluation is not available.

A comparative study to evaluate the safety and immunogenicity of two lots of Haemophilus influenzae type-B conjugate vaccine manufactured at different scales

ObjectiveTo compare the immunogenicity and safety of two different lots of SII Haemophilus influenzae type-B–tetanus toxoid conjugate (SII HibPRO) vaccine manufactured at different scales when given in 3-dose schedule. DesignPhase IV, open label, comparative, randomized parallel group study. SettingShirdi Sai Baba Hospital, Vadu Budruk, Pune and Pediatrics Department of King Edward Memorial Hospital Research Centre, Pune. Subjects204 normal healthy infants of age 6–8 weeks at the time of first vaccination. MethodsThe eligible subjects received 3 doses of 0.5ml of SII HibPRO vaccine of either lot depending upon randomization number, intramuscularly in right thigh in the EPI schedule of 6, 10 and 14 weeks. They also received concomitantly DTP-HB vaccine intramuscularly on left thigh and Oral Polio vaccine (OPV). Solicited reactions were captured for 7 days following each vaccination; the events beyond 7 days till day 28 were captured as unsolicited adverse events. Serious Adverse Events (SAEs) were looked for throughout the subject participation. Blood samples were collected at baseline (before the first dose) and one month after the third dose for anti-PRP (polyribosylribitol phosphate) antibodies. ResultsIn both groups, more than 98% subjects achieved short-term seroprotection (anti-PRP≥0.15μg/ml) after 3 doses. The long-term seroprotection (anti-PRP≥1μg/ml) was 87% and 80% in infants receiving lot manufactured at industrial scale and small scale respectively. Short and long term seroprotection and GMTs increased significantly as compared to baseline in both the groups. Overall local pain (52% and 58%), redness (30% and 41%), swelling (34% and 44%), fever (6% and 6%) and irritability (52% and 50%) were reported in infants receiving lot manufactured at industrial scale and small scale respectively. Majority of the reactions were mild and resoled without any sequelae. Four SAEs, none of them causally related to the study vaccine, occurred during study. ConclusionSII HibPRO vaccines manufactured in small and industrial scale are equally immunogenic, safe and confer adequate seroprotection to infants of 6–14 weeks of age. Scaling up production process has not affected the safety and immune response in the target population.

Associations between Vaccination and Childhood Cancers in Texas Regions

To determine whether children born in Texas regions with higher vaccination coverage had reduced risk of childhood cancer. The Texas Cancer Registry identified 2800 cases diagnosed from 1995 to 2006 who were (1) born in Texas and (2) diagnosed at ages 2 to 17 years. The state birth certificate data were used to identify 11 200 age- and sex-matched control subjects. A multilevel mixed-effects regression model compared vaccination rates among cases and control subjects at the public health region and county level. Children born in counties with higher hepatitis B vaccine coverage had lower odds of all cancers combined (OR = 0.81, 95% CI: 0.67 to 0.98) and acute lymphoblastic leukemia (ALL) specifically (OR = 0.63, 95% CI: 0.46 to 0.88). A decreased odds for ALL also was associated at the county level with higher rates of the inactivated poliovirus vaccine (OR = 0.67, 95% CI: 0.49 to 0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44 to 0.87). Children born in public health regions with higher coverage levels of the Haemophilus influenzae type b-conjugate vaccine had lower odds of ALL (OR: 0.58; 95% CI: 0.42 to 0.82). Some common childhood vaccines appear to be protective against ALL at the population level.

Antibody Response to Polysaccharide Conjugate Vaccines after Nonmyeloablative Allogeneic Stem Cell Transplantation

After allogeneic stem cell transplantation with reduced-intensity conditioning regimens (allo-RIST) patients are susceptible to bacterial and viral infections for a period that may last several years. The efficacy of the recommended vaccination schedules, in terms of induction of a protective antibody response, is unknown. In this study, the reconstitution of humoral immunity after allo-RIST is determined by measuring the vaccination-induced antibody response against Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and tetanus toxoid (TT) 1 year posttransplantation. Patients who underwent allo-RIST were vaccinated according to a schedule starting at 12 months following transplantation with conjugated vaccines against S. pneumoniae, Hib, and TT. Of twenty-six patients both pre- and postvaccination sera were available. Patients were required to be off immunosuppression at the time of vaccination, and, therefore, 9 of the 26 patients did not start vaccination at 12 months post-stem cell transplantation but rather at a median range of 15 (12-36 months) posttransplantation. Except for pneumococcal serotype 6B, more than 73% of the patients developed antibody levels >or=0.35 microg/mL for all pneumococcal serotypes included in the vaccine. For Hib and TT, protective antibody levels were found in 77% and 96% of the patients, respectively. Vaccination of patients at a median of 15 months post-allo-RIST leads to significant rise in concentrations of pneumococcal, Hib, and TT antibodies in the majority of patients.

Immunogenicity and safety of a DTaP-IPV//PRP approximately T combination vaccine given with hepatitis B vaccine: a randomized open-label trial.

To determine seroprotection and vaccine response rates produced by a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type-b conjugate (DTaP-IPV//PRP approximately T) vaccine containing a polyribosyl-ribitol-phosphate (PRP)-tetanus toxoid conjugate (Pentaxim) and given with a hepatitis B vaccine. In this multicentre open-label trial, 424 infants who received DTaP-IPV//PRP approximately T at 6, 10 and 14 weeks of age were also randomized to receive hepatitis B vaccine at either 6, 10 and 14 weeks or 0, 6 and 14 weeks of age. Antibody levels were determined at 6 and 18 weeks of age, and reactogenicity was monitored using parental reports. Immunogenicity was high for all vaccine antigens and was similar to that in a historical control study. After primary vaccination, 98.7% of all infants had an anti-PRP antibody titre > 0.15 microg/ml. Seroprotection against poliovirus type-1, -2 and -3 and tetanus was obtained in all infants, and against diphtheria, in 97.1%. Pertussis seroconversion, defined as a > fourfold increase in antibody titre, occurred in 95.3% for anti-pertussis toxoid antibody and in 89.0% for anti-filamentous haemagglutinin antibody. The hepatitis B seroprotection rate was 99.5% with administration at 0, 6 and 14 weeks, and 97.8%, at 6, 10 and 14 weeks. However, the antibody titre was higher with the 0, 6 and 14-week schedule (601 mIU/ml versus 207 mIU/ml). The reactogenicity of both vaccines was low. The DTaP-IPV//PRP approximately T vaccine was highly immunogenic. The anti-hepatitis B antibody response was seroprotective with both schedules, though the antibody titre was higher with the 0, 6 and 14-week schedule.

Simultaneous vaccination of Chinese applicants for a United States immigrant visa

Simultaneous vaccination is still uncommon in China, and many Chinese people are quite concerned about the adverse reactions because few data regarding the adverse reactions of simultaneous vaccination in Chinese people have been reported. The objective of this study was to evaluate the safety of simultaneous vaccination and the frequency of adverse reactions following simultaneous vaccinations in Chinese applicants for a United States immigrant visa. We conducted a prospective observational study in 772 applicants receiving required vaccination in Guangdong International Travel Healthcare Center. The vaccines required for vaccination included diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP), adult formulation tetanus and diphtheria toxoids (Td), haemophilus influenzae type-b conjugate vaccine (Hib), oral polio vaccine (OPV), hepatitis B vaccine (HepB), combined measles mumps rubella vaccine (MMR), varicella vaccine (Var), and influenza vaccine (Inf), pneumococcal polysaccharide vaccine (PPV). Data on adverse reactions were collected by questionnaires. Seven hundred and seventy-two participants have received a total of 2533 doses of different vaccines, and 49.6% of the participants reported adverse reactions within 7 days following vaccination, with 39.8%(307/772) local reactions and 20.2%(156/772) systemic reactions. There were no allergic reactions. Only one vaccinee visited hospital seeking treatment due to fever, and recovered well. The most frequent local reaction was pain at the injection site (260/772, 33.7%), especially in the case of PPV vaccination, 61.2% (63/103) vaccinees who received PPV complained of pain at the site of injection, while the most frequent systemic reaction was fever (84/772, 10.9%). Pain and fever were all temporary reactions and resolved within 72h. Logistic regression analysis found that females experienced adverse reactions more frequently than males [(local reactions: female:male=41.7%(187/448):37%(120/324), p=0.04; systemic reactions: female:male=23%(103/448):16.4%(53/324), p=0.026)]; vaccinees given PPV developed local reactions more frequently than those receiving the other vaccines. The number of vaccines has no significant influence on adverse reactions. Simultaneous vaccination is feasible for Chinese applicants for a United States immigrant visa because the adverse reactions are mostly mild and temporary. Our data suggest that more Chinese people should be encouraged to receive simultaneous vaccination if the time is limited so as to reduce the risk of vaccine-preventable diseases.