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

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‐γ 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‐γ production upon TT‐stimulation in vitro was also reflected in reduced IFN‐γ/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.