Infanrix Hexa (diphtheria tetanus toxoids, acellular pertussis, hepatitis B (recombinant), inactivated poliomyelitis, adsorbed conjugated Haemophilus influenzae type b vaccine) / GSK - LARVOL DELTA

PRELIMINARY ANALYSIS OF PRE-BOOSTER IMMUNE RESPONSE TO HEXAVALENT VACCINES FOLLOWING THREE-DOSE PRIME VACCINATION IN PRETERM INFANTS (ESPID 2025) - "Methods UK-based infants receiving a three-dose Infanrix hexa (Hex-I) or Vaxelis (Hex-V) hexavalent vaccine schedule at 2-3-4 months were recruited at 12-months and not given Hib/MenC. Sample analysis is ongoing; more samples expected by May 2025. Conclusions/Learning Points These preliminary data suggest that infants born preterm have lower anti-PRP antibodies at 18-months than term infants and could be at increased risk of Hib infection prior to booster vaccination."

Prematurity • Hepatitis B • Infectious Disease • Influenza • Pertussis

Bifidobacteria support optimal infant vaccine responses. (PubMed, Nature) - "Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age...In preclinical models, responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units. Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity."

Journal • Infectious Disease • Influenza • Pneumococcal Infections • Respiratory Diseases

Acellular Pertussis Vaccine Given in the Week After Birth Does Not Impair Antibody Responses to Later Childhood Doses. (PubMed, Pediatr Infect Dis J) - "A birth dose of acellular pertussis vaccine does not impair antibody responses to booster doses of pertussis vaccines and may be an alternative for protection against early infant pertussis when pertussis booster has not been administered during pregnancy."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pertussis • Respiratory Diseases • Tetanus

A Study on the Safety and Immune Responses to the GVGH altSonflex1-2-3 Vaccine Against Shigellosis in Adults, Children, and Infants (clinicaltrials.gov) - P1 | N=552 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting | Phase classification: P1/2 ➔ P1

Enrollment closed • Phase classification

A Study on the Immune Response and Safety of a Multicomponent Shigella Vaccine in Preventing Shigellosis in Infants (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open

Safety and Immunogenicity of an Investigational Pentavalent Meningococcal ABCYW Vaccine Against Meningococcal Disease in Children, Toddlers, and Infants (clinicaltrials.gov) - P1/2 | N=750 | Recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Meningococcal Infections • Pediatrics

A study on the immunogenicity and safety of a multicomponent Shigella vaccine in preventing shigellosis in infants (clinicaltrialsregister.eu) - P2 | N=200 | Sponsor: GlaxoSmithKline Biologicals

New P2 trial • Dermatology • Infectious Disease

A Study on the Immune Response and Safety of a Multicomponent Shigella Vaccine in Preventing Shigellosis in Infants (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial

Safety and Immunogenicity of an Investigational Pentavalent Meningococcal ABCYW Vaccine Against Meningococcal Disease in Children, Toddlers, and Infants (clinicaltrials.gov) - P1/2 | N=750 | Not yet recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company

New P1/2 trial • Infectious Disease • Meningococcal Infections • Pediatrics

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial. (PubMed, PLoS Med) - "In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia)...https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371998&isReview=true. Just one registry (as above)."

Head-to-Head • Journal • Allergy • Food Hypersensitivity • Immunology • Infectious Disease • Pertussis • Respiratory Diseases • Tetanus

A study on the safety, reactogenicity, and immune response to the GVGH iNTS-GMMA vaccine against invasive nontyphoidal Salmonella in adults, children, and infants. (clinicaltrialsregister.eu) - P1/2 | N=516 | Sponsor: GLAXOSMITHKLINE BIOLOGICALS SA

New P1/2 trial • Dermatology • Infectious Disease

EARLY-LIFE ANTIBIOTIC EXPOSURES LEADS TO IMPAIRED ANTIBODY RESPONSES TO PNEUMOCOCCAL VACCINATION ASSOCIATED WITH DEPLETION OF BIFIDOBACTERIUM IN THE INFANT GUT MICROBIOTA. (ISPPD 2024) - "This study assessed the impact of perinatal antibiotic exposure on infant vaccine-specific antibody responses We prospectively enrolled term infants who received 3 doses of Prevenar 13 (PCV13) and Infanrix-hexa vaccines at 6 weeks-4-6 months and 2 doses of rotavirus vaccine (Rotarix). Perinatal antibiotic exposure influences gut microbiome which may affect infant vaccine responses and probiotics may improve responses in these infants."

Gut Microbiota • Pneumococcal vaccines • Infectious Disease • Pneumococcal Infections • Rotavirus Infections

A Study on the Safety, Reactogenicity, and Immune Response to the GVGH iNTS-GMMA Vaccine Against Invasive Nontyphoidal Salmonella in Adults, Children, and Infants (clinicaltrials.gov) - P2 | N=516 | Recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Infectious Disease

Tdap vaccine in pregnancy and immunogenicity of pertussis and pneumococcal vaccines in children: What is the impact of different immunization schedules? (PubMed, Vaccine) - "Infant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children's protection."

Journal • Pneumococcal vaccines • Infectious Disease • Pertussis • Pneumococcal Infections • Respiratory Diseases

Persistence of immunity to 4 years of age following a delayed pertussis vaccine schedule in infancy (ANZCTR) - P=N/A | N=60 | Completed | Sponsor: The Sydney Children's Hospital Network | Initiation date: May 2000 ➔ May 2016

Trial initiation date • Infectious Disease • Pertussis • Respiratory Diseases

Immunogenicity of the pentavalent DTwP-HB-Hib vaccine (Shan-5) used in the Thai Expanded Program on Immunization compared to the hexavalent DTaP-HB-Hib-IPV and DTwP-HB-Hib (Quinvaxem) vaccines administered to infants at 2, 4, 6 months of age. (PubMed, Vaccine) - "The immunogenicity of the HepB surface antigen in the EPI Shan-5 vaccine was similar to that achieved by the hexavalent vaccine, but was higher than that achieved by the Quinvaxem vaccine. The Shan-5 vaccine is highly immunogenic and generates robust antibody responses after primary immunization."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pertussis • Respiratory Diseases • Tetanus

INTERCHANGES OF HEXAVALENT VACCINES, DATA FROM THE FRENCH PEDIATRIC AMBULATORY RESEARCH IN INFECTIOUS DISEASES (PARI) (ESPID 2023) - "In France, two hexavalent vaccines have been marketed for many years, Infanrix Hexa® (IH) and Hexyon® (H), whereas Vaxelis® (V) has been available since April 2018. Among the 41,750 hexavalent doses administered (including 7% preterm infants [<37 weeks]), H represented the majority (63.1%), followed by V (21.5%) and IH (15.5%). For preterms ≤ 32 weeks, the distribution was about 50% each for IH and H. Among the 5,843 children who received 2 doses of hexavalent, H+H represented 62%, V+V, 20% and I+I, 14% of the schedules while interchangeability accounted for 4% with 6 different combinations observed. Among the 8,675 children who received 3 doses of hexavalent, H+H+H represented 61% of the schedules, V+V+V, 21%, I+I+I,13% and interchangeability accounted for 5% with 18 different combinations observed."

Clinical • Infectious Disease • Pediatrics

A Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK)'s Infanrix Hexa Vaccine (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis Vaccine (DTaP5-HBV-IPV-Hib) in Healthy Infants and Toddlers (clinicaltrials.gov) - P4 | N=500 | Completed | Sponsor: GlaxoSmithKline | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease

A review of the DTaP-IPV-HB-PRP-T Hexavalent vaccine in pediatric patients. (PubMed, Expert Rev Vaccines) - "Hexaxim can be given as a booster for infants primed with Infanrix Hexa and given in a pentavalent-hexavalent-pentavalent series. It is an acceptable alternative to other hexavalent vaccines on the market. Further studies are required on the use in immunocompromised patients as well as the antibody persistence of each of the vaccine components."

Journal • Review • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Influenza • Pediatrics • Pertussis • Respiratory Diseases • Tetanus

A Randomized Trial Assessing the Immunogenicity and Reactogenicity of Two Hexavalent Infant Vaccines Concomitantly Administered With Group B Meningococcal Vaccine. (PubMed, Pediatr Infect Dis J) - "These data support flexibility in the use of either Hex-IH or Hex-V in infant immunization schedules containing 4CMenB, with the possibility that Hex-V may enhance protection against Hib."

Journal • Infectious Disease • Influenza • Meningococcal Infections • Respiratory Diseases

MET52: Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine in Infants and Toddlers When Administered Concomitantly With Routine Pediatric Vaccines in the United Kingdom (clinicaltrials.gov) - P3 | N=788 | Active, not recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Meningococcal Infections • Pediatrics

An Individual Patient Data-Based Meta-Analysis of the Relative Reactogenicity of the Infant Doses of Two Licensed Dtap-Backboned Hexavalent Vaccines (ISPOR 2022) - "Having access to individual subject data of six randomized head-to-head controlled trials of two hexavalent vaccines [DTaP-IPV-HB-PRP~T (Hexaxim) and DTaP-IPV-HB//PRP~T (Infanrix-Hexa)] we ran an IPD-MA to describe the relative safety profile of the two hexavalent vaccines based on a list of specific safety endpoints. DTaP-backboned hexavalent vaccines are safe and, depending on the safety endpoint explored, some minor differences (all RRs were close to 1) in favor of one vaccine over the other were noted. As AEs were solicited, they may not reflect what HCPs and parents may consider significant AE in real life. Translated in daily medical practice these differences are clinically meaningless and should not constitute an argument in favor of one vaccine over the other."

Retrospective data • Pain

A Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK)'s Infanrix Hexa Vaccine (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis Vaccine (DTaP5-HBV-IPV-Hib) in Healthy Infants and Toddlers (clinicaltrials.gov) - P4 | N=500 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease

COST IMPLICATION OF INTRODUCING A FULLY LIQUID READY-TO-USE PEDIATRIC HEXAVALENT VACCINE IN NORWAY (ESPID 2022) - "A HV containing powder and suspension for reconstitution, protecting against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and Haemophilus influenzae type b diseases (HV-R; INFANRIX® hexa; DTaP3-HepB-IPV/Hib; GlaxoSmithKline Biologicals s.a., Rixensart, Belgium) is currently available in Norway. The use of HV-NR versus HV-R resulted in potential savings of Norwegian Krone (NOK) 7,852,720 (2,062,442 – 15,610,424; €769,567 [202,119 – 1,529,822]) over a 5-year time-horizon, resulting primarily from HCP costs (46%), vaccine acquisition costs (32%; 28% and 4% attributable to vaccine wastage from leakage and heat failure), and non-needle-stick injury error costs (21%). Conclusions/Learning Points: Application of an existing BIM to Norway demonstrates potential cost savings from introducing a fully-liquid ready-to-use pediatric hexavalent vaccine of up to NOK 7.9 million over a 5-year time-horizon."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pediatrics • Pertussis • Respiratory Diseases • Tetanus

A RANDOMISED TRIAL ASSESSING THE IMMUNOGENICTY AND REACTOGENICITY OF TWO HEXAVALENT INFANT VACCINES CONCOMITANTLY ADMINISTERED WITH GROUP B MENINGOGOCCAL VACCINE (ESPID 2022) - "Backgrounds: Four hexavalent (DTaP-IPV-Hib-HepB) vaccines are licensed in Europe, only one of which (Vaxelis, Hex-V), uses a meningococcal outer membrane protein complex as a carrier protein for Haemophilus influenza type b (Hib), creating potential interactions with the meningococcal vaccine 4CMenB. : In this single-centre open-label randomised trial, infants were randomised in a 1:1 ratio to receive Hex-V or an alternative hexavalent vaccine (Infanrix-Hexa, Hex-IH) at 2, 3 and 4 months with 4CMenB (2, 4, 12 months) in the UK routine immunisation schedule... Of the 194 participants enrolled, 96 received Hex-V and 98 Hex-IH. Non-inferiority of anti-PRP IgG GMCs at 5 months of age in participants receiving Hex-V was established; GMCs were 23-times higher following 3 doses of Hex-V than 3 doses of Hex-IH (geometric mean ratio (GMR) 23.25; one-sided 95% CI 16.21, -). 78/85 (92%) of Hex-V recipients and 43/87 (49%) of Hex-IH recipients had anti-PRP antibodies ≥1.0 μg/ml..."

Clinical • Infectious Disease • Meningococcal Infections • Respiratory Diseases