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Earlier infantile immune maturation is related to higher DTP vaccine responses in children.

Strömbeck A, Lundell AC, Nordström I, Andersson K, Adlerberth I, Wold AE, Rudin A - Clin Transl Immunology (2016)

Bottom Line: The most apparent multivariate pattern was that higher anti-DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood.Furthermore, lower infantile total T- and B-cell blood counts were associated with higher proportions of circulating CD45RO(+) memory T cells and to lower proportions of α4β7(+) naïve T cells later in childhood.The multivariate findings were corroborated in univariate correlation analyses.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden.

ABSTRACT
There are large inter-individual variations in vaccine-specific antibody responses in children. We sought to investigate whether early-life environmental factors and/or adaptive immune maturation were related to diphtheria-tetanus-pertussis (DTP) vaccine-specific antibody levels at 18 months of age. In the prospective FARMFLORA birth-cohort, including both farming and non-farming families, children were immunized with DTP vaccine at 3, 5 and 12 months of age. DTP vaccine-induced antibody levels were measured in plasma at 18 months of age. Infants' blood samples obtained at birth, 3-5 days, 4, 18 and 36 months and at 8 years of age were analyzed for total CD4(+) T- and B-cell counts, proportions of naïve and memory T and B cells, and fractions of putative regulatory T cells by flow cytometry. Multivariate factor analysis was used to examine associations between immune variables and vaccine responses. The most apparent multivariate pattern was that higher anti-DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood. Furthermore, lower infantile total T- and B-cell blood counts were associated with higher proportions of circulating CD45RO(+) memory T cells and to lower proportions of α4β7(+) naïve T cells later in childhood. The multivariate findings were corroborated in univariate correlation analyses. Sex, delivery mode and dairy farm exposure were unrelated to the magnitude of DTP-specific antibody responses. Our results thus suggest that children with a more mature/activated infantile adaptive immunity respond with higher vaccine-induced anti-DTP antibody levels at 18 months of age.

No MeSH data available.


Related in: MedlinePlus

(a) OPLS-loading column plot displaying the associations between Y, that is, total numbers of B cells at 4 months of age, and X variables, that is, T- and B-cell variables over the first 9 years of life that characterize adaptive immune maturation. X variables with bars projected in the same direction as the respective Y variable are positively associated, whereas parameters in the opposite direction are inversely related to the Y variable. The larger the bar and smaller the error bar, the stronger and more certain is the contribution to the model. VIP values are used to discriminate between important and unimportant predictors for the overall model. The OPLS-loading column plot is based on X variables with VIP values⩾1.32. The quality of the OPLS analysis was based on the parameters R2, that is, how well the variation of the variables is explained by the model, and Q2, that is, how well a variable can be predicted by the model. R2Y=0.40; Q2=0.37. Statistical significant correlations (Spearman's rank correlation test) between Y and X variables are indicated by asterisks in the OPLS analysis. A P-value⩽0.05 was regarded as being statistically significant (*P⩽0.05; **P⩽0.01; ***P⩽0.001 and ****P⩽0.0001). (b–e) Representative univariate correlation plots from the OPLS analysis. (f) Total numbers of blood B cells within the lymphocyte gate at birth, at 3–5 days, at 1, 4, 18, 36 months and at 8 years of age. Horizontal bars indicate medians. ****⩽0.0001, analysis of variance post-test for linear trend. All data regarding B-cell numbers up to 36 months of age in the FARMFLORA study have been published previously by Lundell et al.7
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fig4: (a) OPLS-loading column plot displaying the associations between Y, that is, total numbers of B cells at 4 months of age, and X variables, that is, T- and B-cell variables over the first 9 years of life that characterize adaptive immune maturation. X variables with bars projected in the same direction as the respective Y variable are positively associated, whereas parameters in the opposite direction are inversely related to the Y variable. The larger the bar and smaller the error bar, the stronger and more certain is the contribution to the model. VIP values are used to discriminate between important and unimportant predictors for the overall model. The OPLS-loading column plot is based on X variables with VIP values⩾1.32. The quality of the OPLS analysis was based on the parameters R2, that is, how well the variation of the variables is explained by the model, and Q2, that is, how well a variable can be predicted by the model. R2Y=0.40; Q2=0.37. Statistical significant correlations (Spearman's rank correlation test) between Y and X variables are indicated by asterisks in the OPLS analysis. A P-value⩽0.05 was regarded as being statistically significant (*P⩽0.05; **P⩽0.01; ***P⩽0.001 and ****P⩽0.0001). (b–e) Representative univariate correlation plots from the OPLS analysis. (f) Total numbers of blood B cells within the lymphocyte gate at birth, at 3–5 days, at 1, 4, 18, 36 months and at 8 years of age. Horizontal bars indicate medians. ****⩽0.0001, analysis of variance post-test for linear trend. All data regarding B-cell numbers up to 36 months of age in the FARMFLORA study have been published previously by Lundell et al.7

Mentions: It is not known whether the total numbers of blood lymphocytes are related to the maturation progress of the adaptive immune system in children. The negative correlations observed between total lymphocyte counts and vaccine-induced anti-DTP antibody titers (Figure 2) thus prompted us to investigate whether infantile total lymphocyte counts were related to the development of the adaptive immune system during the first 8 years of life. The final OPLS-loading column plots in Figures 3a and 4a display immune parameters that associate most strongly (variable importance for the projection (VIP) values ⩾1.2), positively or negatively, with total numbers of CD4+ T and B cells at 4 months of age, respectively.


Earlier infantile immune maturation is related to higher DTP vaccine responses in children.

Strömbeck A, Lundell AC, Nordström I, Andersson K, Adlerberth I, Wold AE, Rudin A - Clin Transl Immunology (2016)

(a) OPLS-loading column plot displaying the associations between Y, that is, total numbers of B cells at 4 months of age, and X variables, that is, T- and B-cell variables over the first 9 years of life that characterize adaptive immune maturation. X variables with bars projected in the same direction as the respective Y variable are positively associated, whereas parameters in the opposite direction are inversely related to the Y variable. The larger the bar and smaller the error bar, the stronger and more certain is the contribution to the model. VIP values are used to discriminate between important and unimportant predictors for the overall model. The OPLS-loading column plot is based on X variables with VIP values⩾1.32. The quality of the OPLS analysis was based on the parameters R2, that is, how well the variation of the variables is explained by the model, and Q2, that is, how well a variable can be predicted by the model. R2Y=0.40; Q2=0.37. Statistical significant correlations (Spearman's rank correlation test) between Y and X variables are indicated by asterisks in the OPLS analysis. A P-value⩽0.05 was regarded as being statistically significant (*P⩽0.05; **P⩽0.01; ***P⩽0.001 and ****P⩽0.0001). (b–e) Representative univariate correlation plots from the OPLS analysis. (f) Total numbers of blood B cells within the lymphocyte gate at birth, at 3–5 days, at 1, 4, 18, 36 months and at 8 years of age. Horizontal bars indicate medians. ****⩽0.0001, analysis of variance post-test for linear trend. All data regarding B-cell numbers up to 36 months of age in the FARMFLORA study have been published previously by Lundell et al.7
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4815027&req=5

fig4: (a) OPLS-loading column plot displaying the associations between Y, that is, total numbers of B cells at 4 months of age, and X variables, that is, T- and B-cell variables over the first 9 years of life that characterize adaptive immune maturation. X variables with bars projected in the same direction as the respective Y variable are positively associated, whereas parameters in the opposite direction are inversely related to the Y variable. The larger the bar and smaller the error bar, the stronger and more certain is the contribution to the model. VIP values are used to discriminate between important and unimportant predictors for the overall model. The OPLS-loading column plot is based on X variables with VIP values⩾1.32. The quality of the OPLS analysis was based on the parameters R2, that is, how well the variation of the variables is explained by the model, and Q2, that is, how well a variable can be predicted by the model. R2Y=0.40; Q2=0.37. Statistical significant correlations (Spearman's rank correlation test) between Y and X variables are indicated by asterisks in the OPLS analysis. A P-value⩽0.05 was regarded as being statistically significant (*P⩽0.05; **P⩽0.01; ***P⩽0.001 and ****P⩽0.0001). (b–e) Representative univariate correlation plots from the OPLS analysis. (f) Total numbers of blood B cells within the lymphocyte gate at birth, at 3–5 days, at 1, 4, 18, 36 months and at 8 years of age. Horizontal bars indicate medians. ****⩽0.0001, analysis of variance post-test for linear trend. All data regarding B-cell numbers up to 36 months of age in the FARMFLORA study have been published previously by Lundell et al.7
Mentions: It is not known whether the total numbers of blood lymphocytes are related to the maturation progress of the adaptive immune system in children. The negative correlations observed between total lymphocyte counts and vaccine-induced anti-DTP antibody titers (Figure 2) thus prompted us to investigate whether infantile total lymphocyte counts were related to the development of the adaptive immune system during the first 8 years of life. The final OPLS-loading column plots in Figures 3a and 4a display immune parameters that associate most strongly (variable importance for the projection (VIP) values ⩾1.2), positively or negatively, with total numbers of CD4+ T and B cells at 4 months of age, respectively.

Bottom Line: The most apparent multivariate pattern was that higher anti-DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood.Furthermore, lower infantile total T- and B-cell blood counts were associated with higher proportions of circulating CD45RO(+) memory T cells and to lower proportions of α4β7(+) naïve T cells later in childhood.The multivariate findings were corroborated in univariate correlation analyses.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden.

ABSTRACT
There are large inter-individual variations in vaccine-specific antibody responses in children. We sought to investigate whether early-life environmental factors and/or adaptive immune maturation were related to diphtheria-tetanus-pertussis (DTP) vaccine-specific antibody levels at 18 months of age. In the prospective FARMFLORA birth-cohort, including both farming and non-farming families, children were immunized with DTP vaccine at 3, 5 and 12 months of age. DTP vaccine-induced antibody levels were measured in plasma at 18 months of age. Infants' blood samples obtained at birth, 3-5 days, 4, 18 and 36 months and at 8 years of age were analyzed for total CD4(+) T- and B-cell counts, proportions of naïve and memory T and B cells, and fractions of putative regulatory T cells by flow cytometry. Multivariate factor analysis was used to examine associations between immune variables and vaccine responses. The most apparent multivariate pattern was that higher anti-DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood. Furthermore, lower infantile total T- and B-cell blood counts were associated with higher proportions of circulating CD45RO(+) memory T cells and to lower proportions of α4β7(+) naïve T cells later in childhood. The multivariate findings were corroborated in univariate correlation analyses. Sex, delivery mode and dairy farm exposure were unrelated to the magnitude of DTP-specific antibody responses. Our results thus suggest that children with a more mature/activated infantile adaptive immunity respond with higher vaccine-induced anti-DTP antibody levels at 18 months of age.

No MeSH data available.


Related in: MedlinePlus