Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide-specific antibody response and protective efficacy

Eur J Immunol. 2006 Feb;36(2):287-95. doi: 10.1002/eji.200535102.

Abstract

Immunization with a tetanus-protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1-TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti-PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1-TT responded with proliferation and IFN-gamma secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2-cytokine responses were observed in mice immunized with Pnc1-TT. Impaired IFN-gamma production upon TT-stimulation in vitro was also reflected in reduced IFN-gamma/IL-5 ratio. The IL--5 response correlated with IgG anti-PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier-specific IL-5 production. These results show that immunization with Pnc1-TT induces carrier-specific T cell responses that increase with age and determine the levels of PPS-specific Ab elicited. Whereas a weak and Th2-biased response was observed in neonatal mice, infant mice showed a mixed Th1-Th2 response as observed in adults.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Aging / immunology*
  • Animals
  • Animals, Newborn
  • Antibodies, Bacterial / immunology
  • Antibody Formation / immunology*
  • Immunologic Memory / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / immunology*
  • Polysaccharides, Bacterial / administration & dosage
  • Polysaccharides, Bacterial / immunology*
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology*
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Pneumococcal Vaccines
  • Polysaccharides, Bacterial
  • Tetanus Toxoid
  • Vaccines, Conjugate