Humoral immune response of a pneumococcal conjugate vaccine: Capsular polysaccharide serotype 14—Lysine modified PspA

A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi

“…This was consistent with our earlier results with Vi-DT (Diphtheria Toxoid) conjugates which showed a similar shift [20]. The anti-PspA IgG subclass distribution induced by both un-conjugated and conjugated PspA was also predominantly IgG1 similar to that shown earlier with a PspA conjugate from another group [21].…”

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

“…This modification process incorporates methyl groups in about 70% of the ε-amine groups of PspA lysine residues; methyl incorporation has been proven not to interfere with rPspA immunogenicity (27).…”

“…The strains carrying PspA clade 1 and serotype 3 were shown to be highly pathogenic, causing rapid sepsis and death in the mice, while tests using serotypes different from serotypes 3, 6A, and 6B did not cause disease in the animals (data not shown). In the absence of a suitable pneumococcal disease model, the OPA was the assay of choice for evaluating the functional activity of anti-PspA antibodies (27,40).…”

“…Our group has previously demonstrated that conjugation of recombinant PspA (rPspA) to different PSs either maintains or increases its immunogenicity: (i) rPspA family 1, clade 1, conjugated to PS23F induced higher protection against lethal challenge than the nonconjugated rPspA (52), and (ii) rPspA family 2, clade 3, conjugated to polysaccharide serotype 14 (PS14) induced antibodies with a higher efficiency in complement deposition and higher opsonophagocytic activity than the nonconjugated protein (27). To extend these studies, PS6B was conjugated to rPspA family 1, clade 1, using two different methods of conjugation: the chemical linkage of PS6B either to the carboxyl groups or to the amine groups of rPspA.…”

“…Improved conjugation yields increase the possibility of achieving an affordable manufacturing process. In the studies described herein, the method of conjugation through the carboxyl groups previously described by us (27,52) was extended to the conjugation of PS6B with to rPspA clade 1 (rPspA1), and its efficiency was compared with that of reductive amination, a classical method used to obtain PCV7 and PCV13.…”