Hexavalent vaccines: What can we learn from head-to-head studies?

Background: Three hexavalent vaccines against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib) are licensed in Europe: Infanrix hexa (DT3aP-HBV-IPV/Hib), Hexyon (DT2aP-HBV-IPV-Hib) and Vaxelis (DT5aP-HBV-IPV-Hib).

Methods: A systematic literature search was performed in various electronic databases to identify published peer-reviewed head-to-head studies comparing any licensed hexavalent vaccine to another.

Results: Predefined inclusion criteria were met by 12 articles.

Infant vaccine co-administration: review of 18 years of experience with GSK's hexavalent vaccine co-administered with routine childhood vaccines.

Introduction: The benefits of vaccine co-administration include improved vaccine acceptance and uptake resulting in an increased coverage and protection against multiple childhood diseases, with minimal medical visits. The diphtheria-tetanus-acellular pertussis-hepatitis B-poliomyelitis- type b vaccine (DTaP-HBV-IPV/Hib) has been available for more than 19 years and is recommended for co-administration with several other infant vaccines.

Areas Covered: This is a comprehensive review (34 studies, 21,000 participants) describing the immunogenicity and safety of DTaP-HBV-IPV/Hib when co-administered with 12 different vaccines in infants including pneumococcal, meningococcal, rotavirus or measles-mumps-rubella-varicella.

Immunogenicity and safety of a combined DTPa-IPV/Hib vaccine administered as a three-dose primary vaccination course and a booster dose in healthy children in Russia: a phase III, non-randomized, open-label study.

We assessed the immunogenicity and safety of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus/ type b vaccine (DTPa-IPV/Hib) in children in Russian Federation aiming to support the registration of the vaccine in Russia. In this phase 3, non-randomized, open-label study (NCT02858440), healthy children received three primary doses at 3, 4.5, and 6 months of age (N = 235) and a booster dose at 18 months of age (N = 225).

Integration of hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliomyelitis and Haemophilus influenzae type b conjugate vaccine within existing national recommendations following a birth dose of monovalent hepatitis B virus vaccine: results of a systematic review in the Asia Pacific region.

: In Asia Pacific, most countries recommend a monovalent hepatitis B virus (HBV) vaccine dose at birth followed by primary vaccination series including three or four doses of combination vaccines against diphtheria, tetanus, and pertussis, with or without type b (Hib), HBV or poliomyelitis antigens. If hexavalent conjugate vaccines against diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Hib (DTPa-HBV-IPV/Hib) replace the vaccines included in the primary vaccination series, co-administration of lower-valent vaccines would be avoided but infants would receive ≥4 doses of HBV-containing vaccines before the age of 2 years. : We searched for clinical trials conducted in the South-East Asia and Western Pacific Regions (World Health Organization geographic definition), investigating vaccination regimens with >3 doses of HBV-containing vaccines in infants, including a monovalent HBV vaccine birth dose and ≥1 dose of GSK's hexavalent DTPa-HBV-IPV/Hib vaccine.

Immunogenicity and safety following primary and booster vaccination with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccine: a randomized trial in the United States.

Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis and Haemophilus influenzae type b vaccine (DTaP-HBV-IPV/Hib) can further reduce the number of injections in pediatric immunization schedules of countries currently using pentavalent DTaP combination vaccines. This open-label, randomized, multicenter study (NCT02096263) conducted in the United States evaluated the immunogenicity and safety of DTaP-HBV-IPV/Hib vaccine compared with concomitant administration of DTaP-HBV-IPV and Hib or DTaP-IPV/Hib and HBV vaccines. We randomized (1:1:1) infants to receive 3-dose priming with DTaP-HBV-IPV/Hib boosted with DTaP+ Hib, DTaP-HBV-IPV+ Hib boosted with DTaP+ Hib, or DTaP-IPV/Hib+ HBV boosted with DTaP-IPV/Hib, at 2, 4, 6, and 15-18 months of age.

Long-term antibody persistence against hepatitis B in adolescents 14-15-years of age vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy.

We evaluated antibody persistence against hepatitis B virus (HBV) in adolescents previously vaccinated with a hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib), as part of the national newborn immunization program in Germany. We also assessed the anamnestic response to a challenge dose of a monovalent HBV vaccine. In this phase 4, open-label, non-randomized study (NCT02798952), 302 adolescents aged 14-15 years, primed in their first 2 years of life with 4 DTPa-HBV-IPV/Hib doses, received one challenge dose of monovalent HBV vaccine.

Hexavalent vaccines: increasing options for policy-makers and providers. A review of the data supporting interchangeability (substitution with vaccines containing fewer antigens) and mixed schedules from the same manufacturer.

Introduction: Combination vaccines improve vaccine uptake and open the infant immunization space for additional vaccines. Hexavalent vaccines have been marketed since 2000. Infanrix hexa (combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine, DTPa-HBV-IPV/Hib, GSK) is longest on the market, providing 16 years post-marketing experience.

Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa.

Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DTPa-HBV-IPV/Hib), or B (DTPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12-15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine.