Humoral Immune Response of a Pneumococcal Conjugate Vaccine: Capsular Polysaccharide Serotype 14-Lysine Modified PspA

Vaccine. 2011 Nov 3;29(47):8689-95. doi: 10.1016/j.vaccine.2011.08.109. Epub 2011 Sep 9.

Abstract

Polysaccharide-protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the specificity of the reaction between protein and polysaccharide, inhibiting polymerization and the gel formation reaction. In the synthesis process, the currently used activator, 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) was substituted for 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). BALB/c mice were immunized with either the PS14-mPspA conjugate or the co-administered components in a three dose regimen and sera from the immunized animals were assayed for immunity induced against both antigens: PS14 and mPspA. Modification of more than 70% of lysine residues from PspA (mPspA) did not interfere in the immune response as evaluated by the anti-PspA titer and C3 complement deposition assay. Sera of mice immunized with conjugated PS14-mPspA showed similar IgG titers, avidity and isotype profile as compared to controls immunized with PspA or mPspA alone. The complement deposition was higher in the sera of mice immunized with the conjugate vaccine and the opsonophagocytic activity was similar for both sera. Conjugation improved the immune response against PS14. The anti PS14 IgG titer was higher in sera of mice immunized with the conjugate than with co-administered antigens and presented an increased avidity index, induction of a predominant IgG1 isotype and increased complement deposition on a bacteria with a surface serotype 14. These results strongly support the use of PspA as carrier in a conjugate vaccine where both components act as antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology*
  • Complement System Proteins / immunology
  • Female
  • Immunoglobulin G / blood
  • Lysine / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Opsonin Proteins / blood
  • Phagocytosis
  • Pneumococcal Vaccines / administration & dosage*
  • Pneumococcal Vaccines / chemistry
  • Pneumococcal Vaccines / immunology*
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / immunology*
  • Vaccination / methods
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / chemistry
  • Vaccines, Conjugate / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • Immunoglobulin G
  • Opsonin Proteins
  • Pneumococcal Vaccines
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate
  • pneumococcal surface protein A
  • Complement System Proteins
  • Lysine