Polysaccharide: Influence of Carriers and Adjuvants on Isotype Distribution

This project investigated the effects of novel carriers and adjuvants on the isotype of murine immunoglobulin G (IgG) antibody to pneumococcal capsular polysaccharide type 14 (S14PS). S14PS conjugated to bovine serum albumin induced a weak antibody response which was 100 % IgGl following injection without adjuvant. The same polysaccharide conjugated to flagella of Salmonella typhi induced an antibody response which was 88% IgG3. S14PS-bovine serum albumin was injected with block copolymer L121 or Quil A in squalane-in-water emulsions. The copolymer L121 was at least as effective as Quil A or complete Freund adjuvant in inducing IgG antibodies. IgGl was the dominant subclass for all. Addition of monophosphoryl lipid A, but not the threonyl derivative of muramyl dipeptide or nontoxic Rhodopseudomonas sphaeroides lipopolysaccharide, to copolymer L121 increased production of the IgG2a, IgG2b, and IgG3 subclasses. S14PS-flagella with copolymer L121 induced higher titers with a markedly altered isotype distribution: 13 % IgGl, 52 % IgG2a, 6 % IgG2b, and 29 % IgG3. Monophosphoryl lipid A added to L121 reduced IgGl antibody to 5%, but increased IgG2a antibody to 14%, IgG2b antibody to 3%, and IgG3 antibody to 78%. These studies demonstrate that both the carrier and the adjuvant can influence the titer and isotype distribution of antipolysaccharide anti-body responses. Polysaccharides of Streptococcus pneumoniae are thy