Abstract
The evidence for non-specific effects (NSE) of vaccinations on all-cause morbidity and mortality among children is growing. However, our understanding of the underlying mechanisms is still limited. One hypothesis is that NSE are mediated by antibody titers. We used data of 2,123 children from the population-based birth cohort study LISA conducted in Germany to explore whether routine childhood vaccinations and the individual infection history in the first 2 years of life are associated with unrelated antibody titers. We selected 19 exposures (infections and vaccinations) and investigated their association with levels of 12 IgG antibody titers at the age of 2 years. Based on univariable analyses (ANOVA), we identified 21 crude associations between exposures and titers (p < 0.05), while 11 (95%-CI: 6, 17) spurious associations were expected due to multiple testing. In exploratory multivariable analyses, we observed associations between seven investigated IgG titers and 10 exposures; either administered vaccines [e.g., higher anti-hRSV IgG titer in BCG-vaccinated children (regression-coefficient in standard-deviation-units: 0.38; 95%-CI: 0.12, 0.65)] or infections [e.g., higher anti-measles IgG titer in children with reported chickenpox (0.44; 95%-CI: 0.08, 0.80)]. Our results indicate the existence of associations between immunogenic exposures and unrelated antibody titers. Further studies investigating the underlying immunological mechanisms are required.
Highlights
Epidemiological studies in low-income countries suggested that immunization with certain vaccines can have non-specific effects (NSE) on all-cause morbidity and mortality among children (1, 2)
The objective of our study was to investigate whether routine childhood vaccinations and the individual history of infections in the first 2 years of life as well as maternal exposures during pregnancy are associated with the modulation of antibody titer levels against unrelated pathogens at the age of 2 years
Taking missing values into account, 10.6% reported that their children received a Bacillus Calmette-Guérin (BCG) vaccination in the first 2 years of age; 51.0% of the children received a vaccination against MMR while 59.4% a vaccination against hepatitis B, and 86.4% of the children were vaccinated against DTPPHIB (Table 2)
Summary
Epidemiological studies in low-income countries suggested that immunization with certain vaccines can have non-specific effects (NSE) on all-cause morbidity and mortality among children (1, 2). One of the potential mechanisms discussed in the context of NSE is a non-specific modulation of the immune system. This has been supported by several studies showing that the uptake of live attenuated vaccines, such as Bacillus Calmette-Guérin (BCG) against tuberculosis and the vaccine against measles, has been associated with decreased morbidity and mortality to unrelated pathogens (6– 8). The effects should be studied in children, during the development of the immune system Assessing such effects on the antibody responses is complicated by the fact that vaccinations, and infections during infancy and mothers’ exposures during pregnancy can potentially modulate antibody titers (11). The objective of our study was to investigate whether routine childhood vaccinations and the individual history of infections in the first 2 years of life as well as maternal exposures during pregnancy are associated with the modulation of antibody titer levels against unrelated pathogens at the age of 2 years
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