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TB and Pregnancy Impact of Immune Changes of HIV and Stages of Pregnancy on Tuberculosis: Nested Study on Investigating Maternal Antibodies to Modify Infant Tuberculosis Acquisition
Despite high rates of Bacille calmette Guerin (BCG) vaccination to prevent tuberculosis (TB), the World Health Organization estimates that there are 0.5 million new cases of TB among children annually. Infants experience the highest burden of TB morbidity and mortality; up to 40% of children <12 months of age who are infected with Mycobacterium tuberculosis (Mtb) develop TB, and nearly 50% of infants with TB die if untreated. New strategies to prevent infant TB are urgently needed. Maternal vaccination for respiratory pathogens such as influenza and pertussis have resulted in decreased infant mortality, but the impact of maternal humoral TB immunity on infant Mtb acquisition is unknown. The goal of this proposal is to determine if maternal antibodies confer immune protection to infants from Mtb infection. We propose to define Mtb antibody profiles in Indian mothers and their infants, and to evaluate if Mtb antibodies in archived maternal breast milk or infant blood modify infant risk for Mtb infection. These data will inform future studies on maternal vaccination to prevent TB in infancy.
Aim 1: To define the profile of Mtb antibodies among Indian mothers and their infants.
Approach: We will measure Mtb antibody titers (IgA, IgG) and function (antibody-dependent cellular phagocytosis (ADCP)) in 100 Indian mothers and their infants at delivery, 6 weeks, and 6 months of life. We will assess whether maternal HIV and latent tuberculosis infection (LTBI) are associated with Mtb antibody titers and/or function.
Aim 2: Determine if Mtb antibodies in maternal breast milk or infant blood modify risk for infant Mtb infection.
Approach: In a nested case-control study, we will compare Mtb titers and ADCP function in maternal breast milk at 6 weeks postpartum and infant plasma at 6 weeks of life among infants with and without Mtb infection at 1 year of life.