Pregnancy, Arsenic and Immune Response
Condition: Arsenic--Toxicology; Immunologic Disorders Complicating Pregnancy; Vaccine Response Impaired; Micronutrient Deficiency; Influenza
MeSH terms: Influenza, Human; Pregnancy Complications; Immune System Diseases
Study type: Observational

Summary: 
      As the global availability of vaccines increases, and reaches areas disproportionately
      affected by arsenic and malnutrition, resolving questions about potential environmental and
      biologic barriers to maternal immunization has become increasingly urgent. It is not known
      whether arsenic, a known developmental toxicant, can alter maternal immune responses to
      vaccination and whether exposure to arsenic during pregnancy can impair the transfer of
      maternal vaccine-induced antibody to the newborn. Moreover, factors known to affect arsenic
      metabolism and toxicity outcomes, particularly micronutrients critical in one-carbon
      metabolism, have not been evaluated in studies of arsenic immunotoxicity and vaccine-induced
      protection in mothers and their newborns.

      The objective in this study is to investigate whether maternal arsenic exposure and
      one-carbon metabolism micronutrient deficiencies alter maternal and newborn measures of
      vaccine-induced protection, respiratory morbidity, and systemic immune function following
      influenza vaccination during pregnancy.
    

Detailed description: 
      The objective in this study is to investigate whether maternal arsenic exposure and
      one-carbon metabolism micronutrient deficiencies alter maternal and newborn measures of
      vaccine-induced protection, respiratory morbidity, and systemic immune function following
      influenza vaccination during pregnancy. The hypothesis is that maternal arsenic exposure and
      one-carbon metabolism micronutrient deficiencies alter maternal and newborn influenza
      antibody titer and avidity, respiratory infection morbidity, and markers of systemic immune
      function following maternal influenza vaccination during pregnancy. This study leverages a
      comprehensive pregnancy surveillance system at the JiVitA Maternal and Child Health and
      Nutrition Research Project site in Bangladesh (hereafter JiVitA) to pursue the following
      three aims:

      Aim 1. Establish whether arsenic exposure during pregnancy alters maternal and newborn
      influenza antibody titer and avidity following maternal influenza vaccination.

      Aim 2. Determine whether markers of systemic immune function mediate the association between
      arsenic exposure and respiratory illness in pregnant women and their newborns.

      Aim 3. Assess whether arsenic exposure and one-carbon metabolism micronutrient deficiencies
      during pregnancy have a joint effect on markers of systemic immune function and respiratory
      illness in mothers and their newborns.

      This study will yield three expected outcomes. First, it will fill critical knowledge gaps
      about whether arsenic exposure and one-carbon metabolism micronutrient deficiencies alter
      immune responses to a vaccination with known benefits for mothers and their newborns. Second,
      it will increase understanding of arsenic-associated respiratory morbidity and specific
      immune function pathways between arsenic exposure and respiratory morbidity in mothers and
      their newborns. Finally, as the global availability of vaccines increases, improving
      knowledge of potential environmental and biologic barriers to maternal and newborn
      vaccine-induced protection could lead to improved vaccine regimens (targeted vaccination
      campaigns, higher vaccine doses, and/or additional booster immunizations) to restore
      vaccine-induced protection in arsenic-exposed and malnutrition-affected populations of
      pregnant women and newborns worldwide.
    

Intervention name(s): Seasonal influenza vaccine - VAXIGRIP TETRA influenza vaccine (quadrivalent, split virion, inactivated)
Intervention type(s): Biological
Intervention description(s): Influenza virus (quadrivalent, split virion, inactivated) of the strains that comply with the World Health Organization (WHO) recommendations (Northern Hemisphere) and European Union (EU) decision for the 2018/2019 season. The quadrivalent vaccine is propagated in fertilised hens' eggs from healthy chicken flocks.
Intervention MeSH terms: Vaccines
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study will be conducted at the Johns Hopkins JiVitA project site, in the rural
        Gaibandha district, Bangladesh, one of the largest project sites in South Asia, covering
        more than 650,000 people in an area of more than 500 sq. km. Over 150,000 married women of
        reproductive age have been enlisted through thirteen years of previous studies in the area
        with approximately 12% of registered women becoming pregnant each year.
      
Biospecimen description: 
      Venous blood will be collected at a volume of ~24 milliliter (mL) / visit from mothers and
      ~1.5 mL / visit from newborns. Urine will be collected from mother and baby in whatever
      volume is provided at the time. Saliva will be collected in whatever volume is provided using
      the Oracol sampler sponge collection device (Malvern Medical Developments Ldt, Worcester,
      UK). Samples will be transported to the nearest JiVitA field office in a temperature
      monitored cooler on ice within 1hr of collection and processed within 4hrs thereafter.
    
Keywords: Observational; Influenza; Vaccine immunogenicity; Arsenic; Immunology