Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children.

Vaccines have a critical role for the protection against infectious diseases by inducing specific neutralizing IgG antibodies and immunological memory. In Sweden, measles–mumps–rubella (MMR) vaccination is routinely initiated at 18 months with a booster dose at 6–8 years of age, and 95% of all Swedish 2-year-olds have received the vaccine. There is however a notable inter-individual variation in magnitudes of vaccine-specific antibody titers in vaccinated children. Whether these variations are related to the maturation of the adaptive immune system before and close to vaccination is unknown. The adaptive immunity of newborns is essentially naive, given limited exposure to exogenous antigens in utero. Indeed, the majority of CD4+ T cells and B cells in cord blood are naive, that is, express the surface markers CD45RA and CD5, respectively.1, 2, 3, 4, 5 Along with an age-dependent decrease in naive lymphocytes there is an increase in proportions of memory T and B cells that express CD45RO and CD27, respectively.1, 3, 4, 5 This immune maturation progress is paralleled by an enhanced capacity to produce cytokines and with increased total IgG levels in blood.4, 6, 7, 8, 9 Regulatory T cells (Tregs), which express FOXP3 and/or CTLA-4, impede proliferation and cytokine production of other T cells,10, 11, 12, 13 but also have suppressive effects on dendritic cells as well as on B cells and immunoglobulin responses,13, 14, 15 and reviewed in Shevach.16 Whether higher proportions of Tregs in blood hamper the subsequent MMR vaccine-induced antibody titers in children is not known. Early-life environmental factors have been shown to influence adaptive immune maturation. Growing up on a farm is associated with higher proportions of memory T cells and with an enhanced capacity to produce proinflammatory and T helper-associated cytokines.17, 18 Contrary, children born by cesarean section (CS) have lower proportions of memory T cells in childhood.19 Additionally, we have shown that boys have lower B-cell activating factor levels in cord blood than girls, as well as higher proportions of naive B cells at birth and later in childhood.20 Sex-related differences in vaccine-specific antibody levels have also been reported, demonstrating that girls present with higher mumps and rubella antibody titers.21, 22 Given that certain early-life environmental factors appear to have profound effects on immune maturation, they may also impact inter-individual variations in vaccine-induced antibody responses observed in children. By studying the FARMFLORA birth cohort, we sought to further explore how environmental factors and postnatal adaptive immune maturation relate to the MMR-specific humoral immune response.