Reduced Poliovirus vaccine neutralising-antibody titres in infants with maternal HIV-exposure

Sanz-Ramos, Marta; Manno, Daniela; Kapambwe, Mirriam; Ndumba, Ida; Musonda, Kunda; Bates, Matthew; Chibumbya, Julia N.; Siame, Joshua; Monze, Mwaka; Filteau, Suzanne; Gompels, Ursula A.; Team, Cignis Study

doi:10.1016/j.vaccine.2013.02.044

Cited by 29 publications

(30 citation statements)

References 34 publications

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“…When compared to Hepatitis C exposed infants, HEU infants have been shown to have lower levels of transferred maternal antibodies at birth and significantly higher total immunoglobulin levels until 2 years of age [46], and it is thought that reduced maternal antibody interference with vaccines may contribute to a stronger vaccine response. However, others studies have reported decreased neutralizing-antibody titres to the oral poliovirus vaccine [47] and diminished response to the Hepatitis B vaccine among HEU infants [48]. Given the uncertainty surrounding B cell function among HEU, it is not clear if our findings of decreased CD19% in the absence of changes to absolute CD19 count are suggestive of an altered overall immunological profile in response to aggravated HIV exposure, or simply represent an isolated finding.…”

Section: Discussionmentioning

confidence: 66%

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

et al. 2014

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BackgroundReports of increased morbidity and mortality from infectious diseases among HIV Exposed Uninfected (HEU) infants have raised concern about a possible underlying immunodeficiency among them. The objective of this study was to assess the immunological profile of HEU infants born to mothers exhibiting different levels of HIV-1 viremia at the time of delivery.MethodsStudy subjects were enrolled in the Centre maternel et infantile sur le SIDA (CMIS) mother-child cohort between 1997 and 2010 (n =585). Infant CD4+ T cell, CD8+ T cell and CD19+ B cell counts were assessed at 2 and 6 months of age, and compared among HEU infants in groups defined by maternal viral load (VL) at the time of delivery (VL < 50 copies/ml, VL 50–1000 copies/ml, and VL > 1000 copies/ml) in a multivariable analysis.ResultsAt 2 months of age, infants born to mothers with VL > 1000 copies/ml had lower CD4+ T cell counts compared to those born to mothers with VL < 50 copies/ml at the time of delivery (44.3% versus 48.3%, p = 0.007, and 2884 vs. 2432 cells/mm3, p = 0.02). These differences remained significant after adjusting for maternal and infant antiretroviral drug use, gender, race and gestational age, and persisted at 6 months of age. There were no differences in CD8+ T cell count or absolute CD19+ B cell count between groups, though higher CD19+ B cell percentage was seen among infants born to mothers with VL > 1000 copies/ml.ConclusionsThese results suggest that exposure to high levels of HIV-1 viremia in utero, even in the absence of perinatal transmission, may affect the infant’s developing immune system. While further work needs to be done to confirm these findings, they reinforce the need for optimal treatment of HIV infected pregnant women, and careful follow-up of HEU infants.

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Section: Discussionmentioning

confidence: 66%

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

et al. 2014

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“…In keeping with previous studies, the investigators noted lower levels of transferred maternal antibodies in the HEU infants; reduced maternal antibody interference with the vaccine may have contributed to their strong vaccine responses. Detailed longitudinal studies in a birth cohort showed no significant impairment of antibody levels following EPI vaccines between HEU and UU infants [94]; other studies have reported conflicting results [95,96]. In one of these studies, low poliovirus vaccine titres was associated with reduced duration of breastfeeding in the HIV-exposed group [96].…”

Section: Do Heu Infants Make Normal Vaccine Responses?mentioning

confidence: 98%

“…Detailed longitudinal studies in a birth cohort showed no significant impairment of antibody levels following EPI vaccines between HEU and UU infants [94]; other studies have reported conflicting results [95,96]. In one of these studies, low poliovirus vaccine titres was associated with reduced duration of breastfeeding in the HIV-exposed group [96]. Thus it remains an open question if and when EPI vaccines elicit adequate antibody responses in HEU infants; in particular, long-lasting B cell memory and antibody quality have not been addressed in detail.…”

Section: Do Heu Infants Make Normal Vaccine Responses?mentioning

confidence: 99%

HIV-exposed uninfected children: a growing population with a vulnerable immune system?

Afran

Garcia-Knight

Nduati

et al. 2014

Clinical and Experimental Immunology

192

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SummaryThrough the successful implementation of policies to prevent mother-tochild-transmission (PMTCT) of HIV-1 infection, children born to HIV-1-infected mothers are now much less likely to acquire HIV-1 infection than previously. Nevertheless, HIV-1-exposed uninfected (HEU) children have substantially increased morbidity and mortality compared with children born to uninfected mothers (unexposed uninfected, UU), predominantly from infectious causes. Moreover, a range of phenotypical and functional immunological differences between HEU and UU children has been reported. As the number of HEU children continues to increase worldwide, two questions with clear public health importance need to be addressed: first, does exposure to HIV-1 and/or ART in utero or during infancy have direct immunological consequences, or are these poor outcomes simply attributable to the obvious disadvantages of being born into an HIV-affected household? Secondly, can we expect improved maternal care and ART regimens during and after pregnancy, together with optimized infant immunization schedules, to reduce the excess morbidity and mortality of HEU children?

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“…Most infant vaccinations elicit protection through neutralizing antibody induction. There are conflicting reports regarding antibody induction in HEU infants with reports of higher[ 8 ] or lower[ 18 ] antibody titres. Reports on vaccine-specific T-cell responses are also conflicting (reviewed in[ 7 ]).…”

Section: Introductionmentioning

confidence: 99%

Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants

et al. 2015

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Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.

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Reduced Poliovirus vaccine neutralising-antibody titres in infants with maternal HIV-exposure

Cited by 29 publications

References 34 publications

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

HIV-exposed uninfected children: a growing population with a vulnerable immune system?

Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants

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