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. 2016 Jun 15;213(12):1996-2004.
doi: 10.1093/infdis/jiw066. Epub 2016 Feb 16.

Maternal Helminth Infection Is Associated With Higher Infant Immunoglobulin A Titers to Antigen in Orally Administered Vaccines

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Maternal Helminth Infection Is Associated With Higher Infant Immunoglobulin A Titers to Antigen in Orally Administered Vaccines

Carolyn E Clark et al. J Infect Dis. .

Abstract

Background: Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system.

Methods: Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection.

Results: Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups.

Conclusions: Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines.

Keywords: IgA; helminth; immunization; maternal; vaccine.

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Figures

Figure 1.
Figure 1.
Flow diagram of birth cohort participants included in this study.
Figure 2.
Figure 2.
Validating multiplex beads to assess plasma immunoglobulin A (IgA) titers after oral administration of rotavirus and polio vaccines. A, Correlation between plasma IgA titers determined by the rotavirus beads in our multiplex assay compared with those determined by the gold standard rotavirus-specific enzyme-linked immunosorbent assay (ELISA). B, Correlation of neutralization titers for poliovirus serotype 3 (OPV3) determined by standard microneutralization assays and plasma titers of total anti-OPV3 IgA by multiplex assay. C, Correlation of plasma titers of anti–poliovirus serotype 1 (OPV1) IgA and anti-OPV3 IgA determined by multiplex assays. In all panels, each circle represents 1 subject. Spearman coefficient (r) and P values represent results of a nonparametric Spearman correlation test.
Figure 3.
Figure 3.
Comparison of vaccine-specific plasma antibody titers between children of mothers with helminth infection (CHel+) and children of mothers without helminth infection (CHel-). A, Plasma immunoglobulin A (IgA) titers specific for orally administered vaccines at 13 months of age (ie, rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 [OPV1] and 3 [OPV3]). B, Plasma immunoglobulin G (IgG) titers specific for parenterally administered vaccines at 13 months of age (diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b [Hib] vaccines). In all graphs, boxes extend between the 25th and 75th percentiles, whiskers indicate the 5th and 95th percentiles, lines indicate median titers, and plus signs indicate mean titer. Where present, dotted lines indicate minimum titers believed to be protective. Not all graphs have a dotted line because not all vaccines have an established minimum protective titer. Abbreviation: B. pertussis, Bordetella pertussis.
Figure 4.
Figure 4.
Percentage of children of mothers with helminth infection (CHel+) and children of mothers without helminth infection (CHel-) achieving a defined threshold of vaccine-specific plasma antibody titers at 13 months of age. A, Primary end points: the orally administered vaccines. The threshold for antirotavirus immunoglobulin A (IgA) titer was defined as 20 U/mL, the titer often used as a cutoff in rotavirus-specific enzyme-linked immunosorbent assays. The threshold for anti–poliovirus serotype 3 (OPV3) IgA titer was defined as 3100 mIU/mL, the titer at which the sensitivity and specificity were highest, as determined by a receiver operating characteristic curve. B, Secondary end points: the parenterally administered vaccines. The thresholds for vaccine-specific immunoglobulin G (IgG) titers were as follows: anti–diphtheria toxoid, 10 mIU/mL; anti–tetanus toxoid, 10 mIU/mL; anti–Bordetella pertussis, 5 IU/mL; anti–measles virus, 120 mIU/mL; anti–rubella virus, 15 mIU/mL; and anti–Haemophilus influenzae b (Hib), 150 ng/mL. These titers were chosen because they are considered to be correlates or surrogates of protection [19].

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