Pregnancy, Arsenic and Immune Response

NCT03930017 | Completed FDA Drug

• 1 other identifier: R01ES026973
• Study Type: observational
• Target: 784
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Arsenic--Toxicology; Immunologic Disorders Complicating Pregnancy; Vaccine Response Impaired; Micronutrient Deficiency; Influenza

Keywords

Observational; Influenza; Vaccine immunogenicity; Arsenic; Immunology

Outcome Measures

Primary Outcomes (7)

• Change in influenza hemagglutination-inhibition (HI) antibody titer

  Influenza hemagglutination-inhibition (HI) antibody titer will be measured in participant's serum.

  Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum

• Mean percent influenza virus antibody avidity

  The accumulated strength of multiple affinities of individual non-covalent binding interactions of influenza-specific antibodies, including avidity of antibodies to seasonal inactivated influenza virus (IIV) strains included in the formulation in Sanofi Pasteur's 2018-2019 seasonal VAXIGRIP® TETRA vaccine.

  Measured at baseline, 28 days post vaccination, birth, and 3 months post-partum

• Seroconversion rate

  The proportion of pregnant women demonstrating seroconversion

  Defined as a post-vaccination HI titer of ≥40 given a pre-vaccination titer ≤10 or, alternatively, a ≥4-fold increase in HI titer between pre-vaccination and post-vaccination sera if the pre-vaccination titer was >10.

• Change in geometric mean HI antibody titer (GMT)

  GMT HI antibody titers will be transformed to binary logarithms, and original values will be divided by 4 (undetectable titer) to set the starting point of the log scale to zero prior to transformation. We will calculate average log2 GMT antibody titers.

  Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum

• Geometric mean ratio of infant:mother HI titer

  Ratio of infant to mother HI titer as a measure of transplacental transfer of influenza antibody.

  Birth and 3 months post-partum

• Change in influenza virus neutralizing antibody titer

  Virus neutralization is measured as a titer calculated based on the highest serum dilution that eliminates virus.

  Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum

• Change in anti-influenza virus total immunoglobulin G (IgG) enzyme immunoassay

  Total IgG antibodies to influenza virus as measured in serum or plasma by enzyme immunoassay

  Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum

Secondary Outcomes (4)

• Maternal influenza-like illness (ILI)

  From date of enrollment visit until date of 3 months postpartum visit, assessed at weekly intervals

• Infant influenza-like illness (ILI)

  From date of birth visit until date of 3 months postpartum visit, assessed at weekly intervals

• Laboratory-confirmed influenza (LCI)

  From date of enrollment visit until date of 3 months postpartum visit, assessed at weekly intervals

• Acute respiratory illness (ARI)

  From date of enrollment visit until date of 3 months postpartum visit, assessed at weekly intervals

Other Outcomes (10)

• Gestational age (GA) at birth

  Within 72 hours of birth

• Newborn anthropometry weight

  Within 72 hours of birth

• Newborn anthropometry length

  Within 72 hours of birth

Interventions

Seasonal influenza vaccine - VAXIGRIP TETRA influenza vaccine (quadrivalent, split virion, inactivated) BIOLOGICAL

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.

Eligibility Criteria

• Age: 13 Years - 45 Years
• Gender Eligibility Details: This is an observational cohort of pregnancy. Thus only females will be enrolled.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• Women who:
• are within 13-16 weeks of gestational age (GA) of pregnancy;
• are between 13 and 45 years of age;
• are married;
• provide informed consent for herself and assent for her unborn child;
• agree to receive the seasonal influenza vaccine (VAXIGRIP® TETRA seasonal quadrivalent inactivated influenza vaccine, Sanofi Pasteur) upon study enrollment.

You may not qualify if:

• Women who:
• have pre-existing immune-related health condition (e.g., immunodeficiency, lupus, chronic infection, or cancer);
• previous or current use of immune-altering drug/therapy (e.g., steroids);
• have already received influenza vaccination for the current season.

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• Sanofi Pasteur, a Sanofi Company: collaborator
• Institute of Epidemiology, Disease Control and Research: collaborator
• Johns Hopkins Bangladesh - The JiVitA Project Site: collaborator
• University of Graz: collaborator
• Columbia University: collaborator
• UNC Gillings School of Global Public Health: collaborator

Study Sites (1)

JiVitA Maternal and Child Health and Nutrition Research Program

Gaibandha, Bangladesh

Location

Related Publications (3)

• Attreed SE, Navas-Acien A, Heaney CD. Arsenic and Immune Response to Infection During Pregnancy and Early Life. Curr Environ Health Rep. 2017 Jun;4(2):229-243. doi: 10.1007/s40572-017-0141-4.

  PMID: 28488132 BACKGROUND

• Heaney CD, Kmush B, Navas-Acien A, Francesconi K, Gossler W, Schulze K, Fairweather D, Mehra S, Nelson KE, Klein SL, Li W, Ali H, Shaikh S, Merrill RD, Wu L, West KP Jr, Christian P, Labrique AB. Arsenic exposure and hepatitis E virus infection during pregnancy. Environ Res. 2015 Oct;142:273-80. doi: 10.1016/j.envres.2015.07.004. Epub 2015 Jul 15.

  PMID: 26186135 BACKGROUND

• Avolio LN, Smith TJS, Navas-Acien A, Kruczynski K, Pisanic N, Randad PR, Detrick B, Fry RC, van Geen A, Goessler W, Karron RA, Klein SL, Ogburn EL, Wills-Karp M, Alland K, Ayesha K, Dyer B, Islam MT, Oguntade HA, Rahman MH, Ali H, Haque R, Shaikh S, Schulze KJ, Muraduzzaman AKM, Alamgir ASM, Flora MS, West KP Jr, Labrique AB, Heaney CD; JiVitA Maternal and Child Health and Nutrition Research Project. The Pregnancy, Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh. Paediatr Perinat Epidemiol. 2023 Feb;37(2):165-178. doi: 10.1111/ppe.12949. Epub 2023 Feb 9.

  PMID: 36756808 DERIVED

Related Links

• JiVitA Maternal and Child Health and Nutrition Research Project Site in Bangladesh
• Institute of Epidemiology and Disease Control Research (IEDCR) collaborator
• Johns Hopkins University (JHU) Center for Human Nutrition
• Johns Hopkins Environmental Health Microbiology and Immunology Laboratory

Biospecimen

Retention: SAMPLES WITH DNA

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.

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Christopher D Heaney, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: April 29, 2019
• Study Start: October 14, 2018
• Primary Completion: January 6, 2020
• Study Completion: January 6, 2020
• Last Updated: January 5, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)