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

Håvard Jakobsen1, Solveig Hannesdottir, Stefania P Bjarnarson

  • 1Department of Immunology, Landspitali - University Hospital, Hringbraut, 101 Reykjavik, Iceland.

European Journal of Immunology
|December 31, 2005
PubMed

Insights

Neonatal and infant mice show reduced antibody responses to pneumococcal conjugate vaccines due to impaired T cell responses to the carrier protein. This age-dependent T cell immunity influences vaccine efficacy.

Area of Science:

  • Immunology
  • Vaccinology
  • Microbiology

Background:

  • Pneumococcal conjugate vaccines (PNCs) are crucial for preventing pneumococcal infections.
  • Neonatal and infant immune responses to PNCs are often suboptimal compared to adults.
  • The role of T cell responses to carrier proteins in neonatal PNC immunity is not fully understood.

Purpose of the Study:

  • To investigate the age-dependent T cell response to the tetanus toxoid (TT) carrier protein in mice immunized with a pneumococcal polysaccharide (PPS)-TT conjugate vaccine (Pnc1-TT).
  • To determine the correlation between carrier-specific T cell responses and anti-PPS antibody production and protective efficacy.

Main Methods:

  • Immunization of neonatal, infant, and adult mice with Pnc1-TT vaccine.
  • In vitro stimulation of spleen cells with TT carrier protein.
  • Measurement of T cell proliferation and cytokine secretion (IFN-gamma, IL-5).
  • Quantification of anti-PPS IgG antibody titers.

Main Results:

  • Spleen cells from adult mice showed robust proliferation and IFN-gamma secretion upon TT stimulation, unlike neonatal and infant mice.
  • Neonatal and infant mice exhibited age-dependent Th2-cytokine (IL-5) responses.
  • Reduced IFN-gamma production and a lower IFN-gamma/IL-5 ratio were observed in younger mice.
  • IL-5 response correlated with anti-PPS IgG titers; lack of PPS antibodies in neonates was linked to absent IL-5 production.
  • Neonatal mice showed a weak, Th2-biased response, while infant mice displayed a mixed Th1-Th2 response.

Conclusions:

  • Carrier-specific T cell responses, particularly IFN-gamma production, mature with age and are critical for effective antibody production against pneumococcal polysaccharide antigens.
  • The Pnc1-TT vaccine elicits age-dependent T cell immunity, influencing the magnitude and quality of the humoral immune response.
  • Understanding these age-related differences in T cell immunity is essential for optimizing vaccine strategies in infants and neonates.

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