Combined immunogenicity data for a new DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) following primary series administration at 2, 4, 6 months of age in Latin America.

The immunogenicity of a primary series of a new, fully liquid DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim), administered at 2, 4, 6 months of age in four clinical studies is reviewed. Immunogenicity data at 1 month after the third vaccination were assessed and pooled from a total of 1270 participants (per-protocol population) in four randomized clinical trials in Argentina, Mexico, and Peru. Hepatitis B vaccine was not administered at birth. All seroprotection (D, T, polio-1, -2, -3, Hep B, PRP-T [Hib]), seroconversion (PT and FHA), and vaccine response (PT and FHA) data were high, and were similar to licensed comparators (pooled SP, SC, and VR rates were 97.1-100%, 96.0-97.0%, and 99.7-99.9%, respectively). These data show the good immunogenicity of this new hexavalent vaccine that can provide the opportunity to increase global compliance to complex pediatric vaccination schedules.

Antibody persistence and booster vaccination of a fully liquid hexavalent vaccine coadministered with measles/mumps/rubella and varicella vaccines at 15-18 months of age in healthy South African infants.

OBJECTIVE: To assess antibody persistence and booster immunogenicity and safety of a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine. METHODS: Phase III, open-label, 2-center trial. Infants previously primed at 6, 10, 14 weeks of age with DTaP-IPV-Hep B-PRP-T either without (group 1: N = 218) or with hepatitis B at birth (group 3: N = 130) or control DTwP-Hib, hepatitis B and oral poliovirus vaccine vaccines (group 2: N = 219) received the same vaccine(s) as booster (except hepatitis B for group 2) at 15-18 months of age, coadministered with measles/mumps/rubella and varicella vaccines (MMR+V). All participants had received measles vaccine at 9 months of age. Antibodies were measured prebooster and 1 month postbooster vaccination. Safety was evaluated from parental reports. Analyses were descriptive. RESULTS: Antibody persistence (seroprotection and concentration) at 15-18 months of age was high for each valence and similar in each group, except for Hep B (highest in group 3 [extra dose of hepatitis B]) and PRP (highest in group 2). Postbooster seroprotection (D, T, IPV, Hep B, PRP) and seroconversion (pertussis toxin and filamentous hemagglutinin) rates were high and similar in each group (excluding Hep B in group 2 [no booster]); geometric mean antibody levels increased markedly in all groups. The response to MMR+V was similar in each group. All vaccines were well tolerated. CONCLUSIONS: A booster dose of the new DTaP-IPV-Hep B-PRP-T vaccine at 15-18 months of age is highly immunogenic and safe compared with licensed comparators, following primary series administration in the Expanded Program on Immunization schedule, with or without a hepatitis B vaccine at birth and coadministered with MMR+V.

Antibody persistence after a primary series of a new DTaP-IPV-Hep B-PRP-T combined vaccine or separate DTaP-IPV//PRP-T and hepatitis B vaccines at 2, 4, and 6 months of age and the effect of a subsequent DTaP-IPV//PRP-T booster vaccination at 18 months of age in healthy Argentinean infants.

OBJECTIVE: To assess antibody persistence after vaccination with a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine at 18 months of age versus licensed DTaP-IPV//PRP-T and hepatitis B (Hep B) vaccines, and to assess the immunogenicity and safety of a subsequent DTaP-IPV//PRP-T booster. METHODS: A phase III, open-label, single-center study was conducted. Infants previously primed with 3 doses of DTaP-IPV-Hep B-PRP-T (Hexaxim: N = 232 [group 1]) or DTaP-IPV//PRP-T and hepatitis B vaccine (Pentaxim + Engerix B Pediatrico: N = 226 [group 2]) at 2, 4, and 6 months of age received a DTaP-IPV//PRP-T booster at 18 months of age. Antibodies were measured before and 1 month after booster vaccination. Safety was evaluated from parental reports. Analyses were descriptive. RESULTS: Antibody persistence was high and similar in each group for each antigen except for Hep B, for which the percentage (95% confidence interval) of participants with a titer of ≥ 10 mIU/mL was higher in group 2 (99.5% [97.5%, 100.0%]) than in group 1 (85.5% [80.3%, 89.8%]). Postbooster seroprotection (diphtheria, tetanus, inactivated poliovirus, polyribosyl-ribitol phosphate) and serconversion (pertussis toxoid, filamentous hemagglutinin) rates were high and similar in each group, and geometric mean antibody concentrations increased markedly in both groups. Safety after the booster vaccination was good and independent of the primary-series vaccine, although one serious adverse event of convulsions was considered to be vaccine related. CONCLUSIONS: The DTaP-IPV/PRP-T booster vaccination at 18 months of age was similarly immunogenic and well tolerated after primary-series vaccination with either the investigational hexavalent vaccine or the reference pentavalent vaccine. This confirms the suitability of a booster vaccination of DTaP-IPV//PRP-T after a primary series of the new DTaP-IPV-Hep B-PRP-T vaccine.

Safety and immunogenicity of an investigational fully liquid hexavalent DTaP-IPV-Hep B-PRP-T vaccine at two, four and six months of age compared with licensed vaccines in Latin America.

OBJECTIVE: This trial assessed the safety of a fully liquid investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine containing 10 µg Hansenula polymorpha-derived recombinant hepatitis B (hep B) antigen for primary vaccination of infants at 2, 4 and 6 months of age compared with licensed comparators. METHODS: Participants received the DTaP-IPV-Hep B-PRP-T vaccine (group 1, N = 1422) or licensed DTwP-Hep B//Hib (Tritanrix-Hep B/Hib) and oral poliovirus vaccines (group 2, N = 711). The incidence of severe fever (≥ 39.6°C rectal equivalent) in the 2 groups was compared statistically; reactogenicity was evaluated from parental reports. Anti-Hep B antibody titers were measured in a subset of participants (no hepatitis B vaccination at birth) 1 month after dose 3. RESULTS: The investigational vaccine was well tolerated. After any dose, fever (rectal equivalent temperature ≥ 38°C) was observed in 74.8% and 92.7% of participants in groups 1 and 2; severe fever was observed in 4.0% and 5.5% of participants. Solicited injection site and systemic reactions were numerically less frequent in group 1 than group 2, although this difference was not assessed statistically. In both groups, all participants included in the immunogenicity analysis achieved anti-Hep B ≥ 10 mIU/mL and ≥ 96.2% of participants achieved anti-Hep B ≥ 100 mIU/mL, although geometric mean titer was approximately 3-fold lower for the investigational vaccine. CONCLUSION: This new, fully liquid acellular pertussis hexavalent vaccine demonstrated less reactogenicity than the licensed comparator whole cell pertussis vaccine and was highly immunogenic for the new Hep B valence.

A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

OBJECTIVES: To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. METHODS: Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. RESULTS: Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. CONCLUSION: These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules.

Immunogenicity and safety of an investigational hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae B conjugate combined vaccine in healthy 2-, 4-, and 6-month-old Argentinean infants.

BACKGROUND AND AIMS: Assessment of a new, fully liquid, investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim, Sanofi Pasteur), containing the same active ingredients as Pentaxim (DTaP-IPV//PRT-T) and 10 µg Hansenula polymorpha-derived recombinant hepatitis B (Hep B) surface antigen, Sanofi Pasteur, in Argentinean infants. METHODS: Infants born to Hep B surface antigen seronegative mothers were randomized to receive the DTaP-IPV-Hep B-PRP-T vaccine or Pentaxim and Engerix B Pediatrico (Hep B monovalent) vaccines at 2, 4, 6 months of age. Antibody titers were measured before and 1 month after 3-month primary vaccination. Noninferiority analyses were performed on seroprotection/seroconversion rates. Safety was evaluated descriptively up to 1 month after primary vaccination. RESULTS: A total of 624 participants were enrolled, 312 participants were randomized to each group, and 604 participants completed the trial. The DTaP-IPV-Hep B-PRP-T vaccine was demonstrated as noninferior to the Pentaxim and Hep B monovalent vaccines with seroprotection/seroconversion rates 1 month postdose 3 for each valence. The anti-Hep B geometric mean titer 1-month postdose 3 for the investigational DTaP-IPV-Hep B-PRP-T primary series was similar to the monovalent Hep B control. The overall incidence of adverse events was similar among the 2 groups. CONCLUSIONS: The new, fully liquid, investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) is highly immunogenic and safe when compared with licensed comparators, warranting further development.

Immunogenicity and safety study of a new DTaP-IPV-Hep B-PRP-T combined vaccine compared to a licensed DTaP-IPV-Hep B//PRP-T comparator, both concomitantly administered with a 7-valent pneumococcal conjugate vaccine at 2, 4, and 6 months of age in Thai infants.

OBJECTIVE: To assess a new, fully-liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine (diphtheria toxoid (D), tetanus toxoid (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (Hep B), and Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (PRP-T) antigens) compared to a licensed DTaP-IPV-Hep B//PRP-T vaccine following primary series co-administration with a 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: This was a randomized, phase III, observer-blind study in Thai infants (N=412), who received DTaP-IPV-Hep B-PRP-T or DTaP-IPV-Hep B//PRP-T at 2, 4, and 6 months of age, co-administered with PCV7. All received Hep B at birth. Non-inferiority for Hep B ≥ 10 mIU/ml and PRP ≥0.15µg/ml was analyzed (DTaP-IPV-Hep B-PRP-T relative to DTaP-IPV-Hep B//PRP-T) at 1 month post-primary. Seroprotection/seroconversion and geometric mean titers (GMTs) were analyzed descriptively for all hexavalent components. Safety was evaluated from parental reports. RESULTS: Anti-Hep B and anti-PRP antibody seroprotection rates were high for DTaP-IPV-Hep B-PRP-T (n=189) and DTaP-IPV-Hep B//PRP-T (n=190), and non-inferiority was demonstrated. Anti-D and anti-T ≥ 0.01 IU/ml, anti-polio types 1, 2, and 3 ≥ 8 (1/dil), and anti-PT and anti-FHA seroconversion were high and similar in each group. For DTaP-IPV-Hep B-PRP-T and DTaP-IPV-Hep B//PRP-T, anti-Hep B ≥ 100 mIU/ml was 98.4% and 99.5% (GMTs 2477 and 2442 mIU/ml), respectively; anti-PRP ≥ 1.0 µg/ml was 85.2% and 71.1% (GMTs 5.07 and 2.41 µg/ml), respectively. Safety profiles were comparable. There were no vaccine-related serious adverse events. CONCLUSIONS: Following co-administration with PCV7 the investigational DTaP-IPV-Hep B-PRP-T vaccine was safe and immunogenic. Non-inferiority to DTaP-IPV-Hep B//PRP-T was shown for Hep B and PRP.

Immunogenicity and safety of an investigational fully liquid hexavalent combination vaccine versus licensed combination vaccines at 6, 10, and 14 weeks of age in healthy South African infants.

BACKGROUND: Assessment of primary vaccination of a new fully liquid, hexavalent investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) in South African infants. METHODS: Infants were randomized to the following at 6, 10, and 14 weeks of age (Expanded Program on Immunization schedule): DTaP-IPV-Hep B-PRP-T (Group 1; N = 286); DTwP-Hib, hepatitis B, and OPV vaccines (Group 2; N = 286); or DTaP-IPV-Hep B-PRP-T vaccine with hepatitis B vaccine at birth (Group 3; N = 143). Antibody titers were measured before vaccination (pertussis toxoid, filamentous hemagglutinin) and postprimary vaccination (all valences). Noninferiority analyses were performed for Group 1 versus Group 2 for seroprotection rates. Safety was evaluated from parental reports. RESULTS: Noninferiority (Group 1 minus Group 2) was demonstrated for anti-HBs, -PRP, -diphtheria, -tetanus, and -polio 1, 2, 3 (lower 95% confidence interval for the difference was -8.20 to 3.46). Anti-HBs antibody titers ≥10 mIU/mL and anti-PRP ≥0.15 µg/mL were ≥95.4% in each group. Seroprotection rates were also high for the other antigens. Seroconversion rates (4-fold increase from pre- to postvaccination) were 93.6%, 83.2%, and 95.1% in Groups 1, 2, and 3, respectively, for anti-pertussis toxoid and 93.1%, 57.7%, and 90.0% for anti-filamentous hemagglutinin. Anti-HBs GMTs were 330, 148, and 1913 mIU/mL for Groups 1, 2, and 3, respectively. Reactogenicity was similar in each group. Fever ≥39.0°C occurred in 1.7%, 0.4%, and 0.0% of infants in Groups 1, 2, and 3, respectively; no extensive limb swelling, hypotonic-hyporesponsive episodes, or vaccine-related serious adverse events were reported. CONCLUSIONS: The new, fully liquid, investigational hexavalent vaccine in the Expanded Program on Immunization schedule, with/without hepatitis B at birth, is highly immunogenic and safe compared with control vaccines, warranting further development.

Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10-45 years.

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10-15 years, 10 microg HBsAg/dose) and one in Uruguay (344 participants aged 16-45 years, 20 microg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers >or=10 mIU/mL; delta non-inferiority limit of -10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10-15 year and 16-45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.