Effect of O Acetylation of Neisseria meningitidis Serogroup A Capsular Polysaccharide on Development of Functional Immune Responses

Abstract

The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis serogroup A polysaccharide (PS) was examined in studies using human sera and mouse immunization.

Discovery and characterization of sialic acid O-acetylation in group BStreptococcus

“…There are several examples where O-acetylation of bacterial polysaccharides appears to alter host immune responses, including O-acetyl groups on the uronic acid residues of Staphylococcus aureus types 5 and 8 (50); glucuronic acid, ManNAc, and glucose residues of Streptococcus pneumoniae 9V (51); ManNAcphosphate residues of N. meningitidis serogroup A (52); Nacetylgalactosaminuronic acid residues of Salmonella typhi Vi (53); and, N-acetylneuraminic acid residues of N. meningitidis serogroup C (54-56) and E. coli K1 (20). In the last two instances mentioned above, the O-acetylation was present on Sia residues of polysialic acid capsules.…”

The Neisseria meningitidis Serogroup A Capsular Polysaccharide O-3 and O-4 Acetyltransferase

“…In some pathogens, O-acetylation of capsules is involved in immune recognition (6,7). For meningococcal serogroup A CPS, there is a dramatic reduction in the immunogenicity of the polysaccharide observed upon removal of the O-acetyl groups by chemical treatment (8).…”

Spontaneous point mutations in the capsule synthesis locus leading to structural and functional changes of the capsule in serogroup A meningococcal populations

“…Neither the anti-A capsule mAb nor the polyclonal anti-capsular antiserum elicited by the ACWY conjugate vaccine Menveo recognized the non-O-acetylated polysaccharide resulting in a complete lack of bactericidal activity of the anti-ACWY capsule antiserum. In line with this, it has been observed [44] that the majority of the antibodies elicited by vaccination with a conjugate serogroup A polysaccharide vaccine were specific for epitopes involving O-acetyl groups. In contrast, the O-acetyl groups on the meningococcal serogroup C polysaccharide are not necessary for induction of protective antibodies [45].…”

“…O-acetylation is an important final step modification of the A polysaccharide polymer, and a dramatic reduction in immunogenicity is associated with the removal of the O-acetyl groups [19,44]. Many pathogenic bacteria are O-acetylated, but CsaC has no homology to other known O-acetyltransferases or to the sialic acid serogroup C, Y, and W capsule O -acetyltransferases (OatC and OatWY) [17].…”