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

(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. Men-ACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.

Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines

“…In a phase III partially blinded, controlled study (where 1170 healthy subjects aged 18 to 25 years were randomized (1:1:1)), two lots of meningococcal ACWY-tetanus toxoid conjugate vaccines (MenACWY-TT) that differed in serogroup A CPS O-acetylation levels respectively (68% vs. 92% O-acetylation), were evaluated in terms of immunogenicity (i.e., rabbit serum bactericidal activity (rSBA)) and safety in comparison to a licensed MenACWY CPS vaccine (82% serogroup A O-acetylation). The MenA-TT conjugate with O-acetylation levels of 68% and 92% resulted in comparable vaccine immunogenicity [ 16 ]. As a matter of fact, all the meningococcal serogroup A conjugate contained in licensed vaccines (MenAfriVac–Serum Indian Institute; Menveo–GSK Vaccines; Menactra–Sanofi Pasteur; Nimenrix–GSK Vaccines (later taken over by Pfizer)) are largely O-acetylated.…”

Structural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A

“…For natural NmA-CPS contained in vaccines, total O -acetylation levels between 68–92% have been reported, of which roughly 10% is 4- O -acetylation 5 , 11 , 12 . To investigate, whether similar levels can be achieved by in vitro O -acetylation, we incubated CsaC with 1 mg of non- O -acetylated polymer in the presence of different donor (acetyl-CoA) to acceptor ratios, with each ManNAc moiety being considered as one acceptor site.…”

Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix™): A review of its immunogenicity, safety, co-administration, and antibody persistence

“…There was no impact on the O-acetylation level and the vaccines were found to be immunogenic with all subjects achieving an rSBA titer >1:8 for all serogroups. 57 Similarly, Halperin et al showed that Men-ACWY-TT with different O-acetylation levels was immunogenic in 1016 subjects aged between 10 and 25 years and was non-inferior to MenACWY-DT for all serogroups. 51 …”