title: Impaired haemophilus influenzae type b transplacental antibody transmission and declining antibody avidity through the first year of life represent potential vulnerabilities for HIV-exposed but -uninfected infants.
abstract: To determine whether immune function is impaired among HIV-exposed but -uninfected (HEU) infants born to HIV-infected mothers and to identify potential vulnerabilities to vaccine-preventable infection, we characterized the mother-to-infant placental transfer of Haemophilus influenzae type b-specific IgG (Hib-IgG) and its levels and avidity after vaccination in Ugandan HEU infants and in HIV-unexposed U.S. infants. Hib-IgG was measured by enzyme-linked immunosorbent assay in 57 Ugandan HIV-infected mothers prenatally and in their vaccinated HEU infants and 14 HIV-unexposed U.S. infants at birth and 12, 24, and 48 weeks of age. Antibody avidity at birth and 48 weeks of age was determined with 1 M ammonium thiocyanate. A median of 43% of maternal Hib-IgG was transferred to HEU infants. Although its level was lower in HEU infants than in U.S. infants at birth (P < 0.001), Hib-IgG was present at protective levels (>1.0 μg/ml) at birth in 90% of HEU infants and all U.S. infants. HEU infants had robust Hib-IgG responses to a primary vaccination. Although Hib-IgG levels declined from 24 to 48 weeks of age in HEU infants, they were higher than those in U.S. infants (P = 0.002). Antibody avidity, comparable at birth, declined by 48 weeks of age in both populations. Early vaccination of HEU infants may limit an initial vulnerability to Hib disease resulting from impaired transplacental antibody transfer. While initial Hib vaccine responses appeared adequate, the confluence of lower antibody avidity and declining Hib-IgG levels in HEU infants by 12 months support Hib booster vaccination at 1 year. Potential immunologic impairments of HEU infants should be considered in the development of vaccine platforms for populations with high maternal HIV prevalence.
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA Center for Global Health, Colorado School of Public Health, Aurora, Colorado, USA james.gaensbauer@childrenscolorado.org.
authors.forename: James T
authors.initials: JT
authors.lastname: Gaensbauer
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA Mucosal and Vaccine Research Colorado (MAVRC), Aurora, Colorado, USA Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Rakhola
authors.affiliation: Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
authors.forename: Carolyne
authors.initials: C
authors.lastname: Onyango-Makumbi
authors.affiliation: Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
authors.forename: Michael
authors.initials: M
authors.lastname: Mubiru
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Westcott
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Krebs
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA Center for Global Health, Colorado School of Public Health, Aurora, Colorado, USA.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Asturias
authors.affiliation: Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
authors.forename: Mary Glenn
authors.initials: MG
authors.lastname: Fowler
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA Mucosal and Vaccine Research Colorado (MAVRC), Aurora, Colorado, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McFarland
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA Mucosal and Vaccine Research Colorado (MAVRC), Aurora, Colorado, USA Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D000915:Antibody Affinity / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D018073:Haemophilus Vaccines / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate
chemical_list: D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D018074:Vaccines, Conjugate