CD4+ T-cell responses among adults and young children in response to Streptococcus pneumoniae and Haemophilus influenzae vaccine candidate protein antigens

• Adults had higher CD4+ T-cell responses to Spn and NTHi antigens compared to very young children.
• CD4+ T-cell responses of very young children to Spn and NTHi antigens were Th-2 predominant.
• Very young children have reduced Th1 and Th2 responses similar to neonates.
• IL-17a producing CD4+ T-cells were rarely detected in response to Spn and NTHi antigens.
• Memory phenotypic profiles of antigen-induced CD4+ T-cells were divergent in adults and children.

We characterized cytokine profiles of CD4+ T-helper (h) cells in adults and young children to ascertain if responses occur to next-generation candidate vaccine antigens PspA, PcpA, PhtD, PhtE, Ply, LytB of Streptococcus pneumonia (Spn) and protein D and OMP26 of non-typeable Haemophilus influenzae (NTHi). Adults had vaccine antigen-specific Th1 and Th2 cells responsive to all antigens evaluated whereas young children had significant numbers of vaccine antigen-specific CD4+ T cells producing IL-2, (p = 0.004). Vaccine antigen-specific CD4+ T-cell populations in adults were largely of effector (TEM) and/or central memory (TCM) phenotypes as defined by CD45RA−CCR7+ or CD45RA−CCR7− respectively; however among young children antigen-specific IL-2 producing CD4+ T cells demonstrated CD45RA+ expression (non-memory cells). We conclude that adults have circulating memory CD4+ T cells (CD45RA−) that can be stimulated by all the tested Spn and NTHi protein vaccine candidate antigens, whereas young children have a more limited response.