The impact of prenatal exposure to persistent organic pollutants on kinetics of immune response to vaccines and sero-protection in infants

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 DESCRIPTION (provided by applicant): Persistent organic pollutants (POPs) are a group of chemically stable compounds that bioaccumulate and persist in the environment, animals and humans. POP toxicities include carcinogenicity, endocrinopathy, neurotoxicity, and immunotoxicity. Although production of POPs was banned in many countries in the 1980s, high levels can be still be detected in the blood of young children worldwide. Significant exposure to POPs can begin in utero, during critical periods of fetal immune system development, and POPs appear to induce numerous immunotoxic effects. There is specific evidence of attenuated responses to immunizations that suggest reduced vaccine efficacy however a comprehensive assessment of the effects of POPs exposure across a panel of routine infant immunizations has not yet been performed. Significant portions of the Chinese population are exposed to a broad array of POPs across a range of exposure levels that are comparable to those in US populations. The public health impact of POP immunotoxicity has been identified as a research priority by the Chinese Centers for Disease Control and Prevention (China CDC), as well as the US National Institutes of Health. We will perform a prospective cohort study in Tianjin China to assess the dependence of vaccine-specific immune responses and risk for infections on prenatal POPs exposure. Specifically, a cohort of 580 healthy pregnant women 20-30 years of age living in the TangGu Districts of Tianjin China will be established in collaboration with the China CDC. Samples of cord blood will be obtained at the time of birth, and cord blood concentrations of a panel of 47 compounds belonging to all major classes of POPs will be assayed to measure prenatal exposure to POPs. Infants will then be followed from birth to 25 months of age, capturing data regarding vaccination history, diagnosis, treatment and outcomes for infections, general health status, growth and development, and non-infectious illness (especially those related to allergic, autoimmune, and cancer). Blood specimens will be taken at multiple time points throughout this period and analyzed for antibody titers/concentrations to a panel of 10 vaccine-specific antigens associated with 5 routine infant immunizations (oral poliovirus vaccine, hepatitis B, hepatitis A, diptheria/pertussus/tetanus, measles/mumps/rubella). Kinetic parameters of the immune response to each vaccine immunogen will be used to summarize longitudinal data. Multivariate regression methods will be used to model the dependence of the immunologic kinetic parameters on levels of exposure to the 47 POPs compounds alone and in combination. The statistical techniques of multiple imputation and group LASSO with cross-validation will be used to identity subsets of POPs compounds within and between classes that are most predictive of the immunologic outcomes. The establishment of clear links between POPs exposure and degraded immune responsiveness will have important implications for disease prevention efforts in China, as well as in the US and around the globe.