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. 2014 Dec;21(12):1661-7.
doi: 10.1128/CVI.00356-14. Epub 2014 Oct 8.

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

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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

James T Gaensbauer et al. Clin Vaccine Immunol. 2014 Dec.

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.

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Figures

FIG 1
FIG 1
H. influenzae type b (A), DT IgG concentration in HIV-infected mothers in Uganda before birth and in their HIV-uninfected infants at birth (B), and percent mother-to-infant Hib and DT IgG antibody transfer (C) (n = 52 mother-infant pairs; P value from Wilcoxon rank sum test).
FIG 2
FIG 2
Correlation of percent transfer of Hib- and DT-specific IgG and concentration of maternal antibody (n = 20 mother-infant pairs; P values from linear regression for each antigen and analysis of covariance for comparison between antigens).
FIG 3
FIG 3
H. influenzae type b antibody concentrations at four time points in the first year of life in Ugandan HIV-exposed but -uninfected (A) and U.S. HIV-unexposed (B) infants (n = 57 Ugandan and 14 U.S. infants).
FIG 4
FIG 4
Avidity in 1 M ammonium thiocyanate of H. influenzae type b IgG from Ugandan HIV-exposed but -uninfected and U.S. HIV-unexposed infants at birth and 1 year of age. The avidity percentage represents the percentage of Hib-specific IgG persistently bound in the presence of 1 M ammonium thiocyanate. A higher percentage represents greater avidity for and strength of binding to the solid-phase Hib capsular PRP antigen. Statistical comparisons are represented by dark horizontal lines; P values are for unpaired t tests (n = 23 Ugandan and 14 U.S. infants). NS, not significant.

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