Immunecorrelates of lower respiratory tract infections in HIV-exposed uninfected infants

Abstract

The NICHD Site Development Initiative (NISDI) perinatal study undertaken in Latin America showed that HIV-exposed, but uninfected infants (HUI) born to HIV-infected mothers have an excess incidence of lower respiratory tract infections (LRTIs), particularly bronchiolitis, that require hospitalization compared with historical data from unexposed infants. To determine the immune correlates that lead to the increased incidence of RTI in HIV-exposed, but uninfected infants (HUI), we formulated the hypotheses: 1-Low maternal antibody transference to the fetus due to HIV infection of the pregnant mother increases the susceptibility of (HUI) to LRTI during the first 6 months of life; 2- HUIs have a deficit of innate or adaptive immunity during the first 6 months of life. -The objectives of this proposal are: 1-To identify the microbiologic agents associated with the increased incidence of LRTI in HUIs; 2-To compare the acquisition of maternal antibodies directed against respiratory agents by HUIs vs. infants born to healthy mothers and between LRTI-affected and unaffected HUIs; 3-To compare humoral and CMI responses to childhood vaccines of HUIs with those of infants born to healthy mothers and between LRTI-affected and unaffected HUIs;4-To compare the Natural Killer function of HUIs with that of infants born to healthy mothers and between LRTI-affected and unaffected HUIs. - The study group will consist of at least 300 Brazilian term (>37 completed weeks of gestation), HUIs enrolled in the NISDI Perinatal Study as of March 1, 2006 who weighed > 2500 grams at birth with no severe underlying conditions who completed six months of follow up. A control group of 100 Brazilian infants born to healthy mothers will be enrolled and followed from birth to 6 months of age similarly to those enrolled in NISDI. Medical history and physical examination with assessment of growth, morbidity, feeding, immunizations, and hospitalizations data will be recorded. Plasma samples will be obtained from the mother before hospital discharge, and from the infant, in the neonatal period and at 6 months of age for verification of the antibody levels against RSV, HMPV, pneumococcus, influenza, PIV1, 2, 3. Cryopreserved PBMC obtained at 6 months of age will be used to evaluate cell-mediated immunity in response to tetanus toxoid vaccine and BCG-Id.- After exploring reasons related to components of children's immunity and better understanding frequently associated agents causing these infections, the findings of this study have the potential of improving clinical management of HUIs in Central and South America. Furthermore, these findings could be useful for means of prevention of infections using available vaccines and/or prophylactic drugs. (AU)