Immune responses of young mice to pneumococcal type 9V polysaccharide-tetanus toxoid conjugate

Abstract

Pneumococcal type 9V polysaccharide (PS), contained in the current pneumococcal vaccine, induces only a weak antibody response in young children and therefore is not an effective vaccine for young children. To increase its immunogenicity, a conjugate of PS to a protein carrier, tetanus toxoid (TT), was prepared. To quantify the immune response, mouse anti-9V PS immunoglobulin G (IgG) and IgM reference standards were established. Young mice immunized at 2 weeks of age produced IgM antibody in response to 9V PS alone or 9V PS conjugated to TT. However, only the 9V PS-TT conjugate induced an IgG antibody response and an anamnestic effect. Thus, a covalent linkage between TT and 9V PS was required for isotype switching from IgM to IgG. 9V PS-TT adsorbed with aluminum hydroxide adjuvant resulted in a fivefold or greater increase in the IgG antibody level. We also studied the effect of maternal immunization on the immune response of young mice to 9V PS-TT. Maternal immunization before mating or before mating and during gestation primed 2-week-old progeny given two injections of 9V PS-YT to produce more IgM antibody than progeny from unimmunized mothers. The IgG antibody level of neonates at birth was similar to that observed in the mothers and was probably passive antibody. These results indicate that maternal immunization with an optimum dose of a PS-protein conjugate before and/or during pregnancy, followed by immunization of the offspring with the conjugate, could provide young children with an enhanced IgM antibody response to pneumococcal PSs.

Humoral Immune Response in Mice Over-expressing or Deficient in Growth Hormone

“…its clinical relevance in vaccine research (47)(48)(49). Relative to nontransgenic (Ntg) siblings that express GH at normal levels (33, 50), MT-bGH20-tg mice grow to adult body weights that are significantly greater (51) and have significantly reduced life spans (25).…”

Cognate Stimulatory B-Cell–T-Cell Interactions Are Critical for T-Cell Help Recruited by Glycoconjugate Vaccines

“…The role of T cells in IgM responses to bacterial CPSs conjugated to proteins is controversial: some investigators have found substantially higher levels of CPS-specific IgM after CPS conjugation to carriers (8,37,63), while others have found minimal or no differences (10,56). It is interesting that in these studies, levels of CPS-specific IgM were substantially higher when high-molecular-weight CPSs isolated from pathogenic bacteria were used as test antigens (8,37,63), whereas minimal or no differences in hapten-or carbohydrate-specific IgM were observed when synthetic haptens or dextran was used (10,56). We found that immunization of T-cell-sufficient mice with high-molecular-weight GBSIII CPS conjugated to TT resulted in substantially higher levels of CPS-specific IgM than did immunization with unconjugated CPS (Table 1).…”

Development of vaccination approaches for the treatment of neurological diseases

“…Employing HSV amplicon technology my group vaccinated AD transgenic mice expressing mutated APP (Tg2576) with amplicons encoding either Ab 1‐42 (HSVAβ) or Ab 1‐42 fused with the molecular adjuvant tetanus toxin Fragment C (HSVAβ/TtxFC) (Bowers et al,2005). TtxFC was selected because it enhances immunogenicity and can skew an immune response toward a humoral T H 2 pathway (Lu et al,1994). The Tg2576 mice vaccinated with HSVAβ/TtxFC generated IgG1 antibodies consistent with T H 2 activation compared with HSVAβ vaccinated mice which initially expressed IgM antibodies followed by IgA isotypes (Bowers et al,2005).…”