Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial.

BACKGROUND: Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate. METHODS: This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination. RESULTS: 1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains. CONCLUSIONS: In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity criteria for adults. CLINICAL TRIAL REGISTRY NUMBER: NCT01481454.

Randomized controlled study of fractional doses of inactivated poliovirus vaccine administered intradermally with a needle in the Philippines.

OBJECTIVE: Comparison of a fractional inactivated poliovirus vaccine (IPV) dose administered intradermally (ID) to a full dose administered intramuscularly (IM). METHODS: Healthy Filipino infants were randomized to receive IPV as either a fractional (1/5(th)) dose ID by needle injection or a full dose IM at 6, 10, and 14 weeks and a booster at 15-18 months of age. Pre- and post-vaccination anti-polio 1, 2, and 3 titers were estimated. Adverse events were monitored throughout the study. RESULTS: Following primary series vaccination, anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in 99-100% of participants, and the ID route was non-inferior to the IM route. Depending on the study group, antibody persistence was detected in 83-100% of participants, and the booster dose resulted in a strong anamnestic response in all groups. The incidence of adverse events in each group was similar, except for injection-site erythema (higher in the ID group). CONCLUSIONS: Primary series and booster vaccination of a fractional IPV dose administered by the ID route was highly immunogenic and well tolerated. These data confirm the medical validity of using fractional ID doses of IPV. The programmatic feasibility of implementing affordable mass vaccination programs based on this delivery mode has yet to be established.

MMR trivalent vaccine based on safety, reactogenicity and immunogenicity observed in 12-24 month-old healthy Filipino children: Evaluation of lot-to-lot consistency of a live-attenuated measles-mumps-rubella

In this double-blind, randomized single-dose study, 194 healthy Filipino children aged 12-24 months were randomized into three groups (1:1:1) to receive one of the three lots of live-attenuated measles-mumps-rubella (MMR) vaccine to assess lot-to-lot consistency in safety and immunogenicity. Adverse events were recorded during 43-day post-vaccination follow-up period. Antibody levels were measured using ELISA pre-vaccination and on Day-60. No statistically significant differences were observed across groups for overall incidences of local and general symptoms (p>0.05) or immune response rates against the three antigens (p=0.835, 0.458 and 0.222 for anti-measles, anti-mumps and anti-rubella, respectively). The three lots demonstrated consistency in their reactogenicity and immunogenicity profile.

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

OBJECTIVE: 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. METHODS: 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. FINDINGS: 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. CONCLUSION: 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.