title: Meningococcal polysaccharide A O-acetylation levels do not impact the immunogenicity of the quadrivalent meningococcal tetanus toxoid conjugate vaccine: results from a randomized, controlled phase III study of healthy adults aged 18 to 25 years.
abstract: In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ≥1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ≥1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.
authors.affiliation: Research Institute for Tropical Medicine, Department of Health, Muntinlupa City, Philippines.
authors.forename: Socorro
authors.initials: S
authors.lastname: Lupisan
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Limkittikul
authors.forename: Nestor
authors.initials: N
authors.lastname: Sosa
authors.forename: Pornthep
authors.initials: P
authors.lastname: Chanthavanich
authors.forename: Véronique
authors.initials: V
authors.lastname: Bianco
authors.forename: Yaela
authors.initials: Y
authors.lastname: Baine
authors.forename: Marie
authors.initials: M
authors.lastname: Van der Wielen
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Miller
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D001770:Blood Bactericidal Activity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005221:Fatigue / Q000453:epidemiology; D005260:Female; D006261:Headache / Q000453:epidemiology; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D010146:Pain / Q000453:epidemiology; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; C043226:meningococcal group A polysaccharide; C576777:tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine