Initiation of Antiretroviral Therapy Before Pregnancy Reduces the Risk of Infection-related Hospitalization in Human Immunodeficiency Virus–exposed Uninfected Infants Born in a High-income Country

Goetghebuer, Tessa; Smolen, Kinga K.; Adler, Catherine; Das, Jishnu; McBride, Trevor; Smits, Gaby; Lecomte, Sandra; Haelterman, Edwige; Barlow, Patricia; Piedra, Pedro A.; Klis, Fiona van der; Kollmann, Tobias R.; Lauffenburger, Douglas A.; Alter, Galit; Levy, Jack S.; Marchant, Arnaud

doi:10.1093/cid/ciy673

Cited by 68 publications

(79 citation statements)

References 35 publications

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“…The study was conducted according to the principles expressed in the declaration of Helsinki, reviewed by the Partners Internal Review Board, and approved by the Partners Human Research Committee (Approval Number 2011P001763). Cohort 2 is part of a study of maternal determinants of infant immunity (Goetghebuer et al, 2018) and was reviewed by the ethics Committee of the Hô pital Saint-Pierre, Belgium and Partners Human Research Committee (Approval Number 2011P001763).…”

Section: Human Serum Samplesmentioning

confidence: 99%

Fc Glycan-Mediated Regulation of Placental Antibody Transfer

Jennewein

Goldfarb

Dolatshahi

et al. 2019

Cell

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185

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Graphical Abstract Highlights d NK cell-activating antibodies are selectively transferred across the placenta d Digalactosylated Fc glycans are preferentially transferred across the placenta d Digalactosylated antibodies bind more effectively to FcRn and FCGR3A d Although immature, neonatal NK cells are highly responsive to immune complexes SUMMARY Despite the worldwide success of vaccination, newborns remain vulnerable to infections. While neonatal vaccination has been hampered by maternal antibody-mediated dampening of immune responses, enhanced regulatory and tolerogenic mechanisms, and immune system immaturity, maternal pre-natal immunization aims to boost neonatal immunity via antibody transfer to the fetus. However, emerging data suggest that antibodies are not transferred equally across the placenta. To understand this, we used systems serology to define Fc features associated with antibody transfer. The Fc-profile of neonatal and maternal antibodies differed, skewed toward natural killer (NK) cell-activating antibodies.This selective transfer was linked to digalactosylated Fc-glycans that selectively bind FcRn and FCGR3A, resulting in transfer of antibodies able to efficiently leverage innate immune cells present at birth. Given emerging data that vaccination may direct antibody glycosylation, our study provides insights for the development of next-generation maternal vaccines designed to elicit antibodies that will most effectively aid neonates. Antibodies against pertussis derived filamentous hemagglutinin (FHA), pertactin (PTN), fimbriae (FIM), and pertussis toxin (PTX) antigens were compared in 14 mother:cord pairs. (A) The flow cytometric plots depict the gating strategy for antibody dependent cellular phagocytosis (ADCP). (B) The connected dot-plot shows the phagocytic activity across mother:cord pairs. (C) The box-and-whisker plot shows the transfer ratio of ADCP. The dotted line indicates a 100% transfer efficiency (equivalent levels across both compartments). (D) The flow plots highlight the gating strategy for antibody dependent neutrophil phagocytosis (ADNP). (E) The dot-plot shows the relationship between ADNP activity across mother:cord pairs for each antigen-specificity. (F) The whisker plots show the transfer ratio for ADNP. (G) The flow plots highlighting the gating strategy for the NK cell activation assay. (H-J) The dot-line plots show NK-dependent degranulation plotted as the percentage of NK cells positive for CD107a (H), IFNg (I), and MIP-1b (J). (K-M) The whisker plots depict the transfer ratio across the three NK cell activation markers, CD107a (K), IFNg (L), and MIP-1b (M).

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Section: Human Serum Samplesmentioning

confidence: 99%

Fc Glycan-Mediated Regulation of Placental Antibody Transfer

Jennewein

Goldfarb

Dolatshahi

et al. 2019

Cell

Self Cite

185

211

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“…This is particularly significant given the increased infectious morbidity and mortality observed in HIV-exposed uninfected as compared to HIV-unexposed infants [120,128]. This notion is supported by a recent study conducted in Belgium, showing an association between reduced transfer of maternal antibodies, as well as immune activation in the newborn, and risk of hospitalization for infection during the first months of life in HIV-exposed uninfected infants [127]. Few studies have examined the impact of maternal HIV infection on the transfer of antibodies induced by vaccination during pregnancy.…”

Section: Impact Of Chronic Maternal Infections On Antibody Transfermentioning

confidence: 82%

“…Studies from low and high income countries reported decreased transfer of maternal IgG in children born to HIV-infected mothers across multiple vaccine and pathogen-specific antigens [119,126,127]. This is particularly significant given the increased infectious morbidity and mortality observed in HIV-exposed uninfected as compared to HIV-unexposed infants [120,128].…”

Section: Impact Of Chronic Maternal Infections On Antibody Transfermentioning

confidence: 99%

“…This variability could be related to differences in the activity of maternal HIV infection across studies. Indeed, higher transfer ratios of maternal antibodies were observed in mothers who initiated anti-retroviral therapy before as compared to during pregnancy [127]. Immunization of HIV-infected pregnant women is an important strategy to protect their vulnerable newborn infants but its efficacy can be limited by reduced vaccine immunogenicity and reduced transfer of maternal antibodies.…”

Section: Impact Of Chronic Maternal Infections On Antibody Transfermentioning

confidence: 99%

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Immunobiological aspects of vaccines in pregnancy: Maternal perspective

Chu

Marchant

2020

Maternal Immunization

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“…Risk of hospitalization was related to time at initiation of antiretroviral therapy in the pregnant women and was predicted by immune alterations measured at birth. The risk for hospitalization was 4-fold higher when mothers initiated therapy during pregnancy but not significantly increased when treatment was started before pregnancy (16).…”

mentioning

confidence: 92%