Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children

Nielsen‐Saines, Karin; Brasil, Patrícia; Kerin, Tara; Vasconcelos, Zilton; Gabaglia, Claudia Raja; Damasceno, Luana; Pone, Marcos Vinícius da Silva; Carvalho, Liège Maria Abreu de; Pone, Sheila Moura; Zin, Andréa; Tsui, Irena; Salles, Tania Regina Saad; Cunha, Denise Cotrim da; Costa, Roozemerie Pereira; Malacarne, Jociele; Reis, Ana Beatriz Rodrigues; Hasue, Renata Hydeé; Aizawa, Carolina Yuri Panvequio; Genovesi, Fernanda Françoso; Einspieler, Christa; Marschik, Peter B.; Pereira, José Paulo; Gaw, Stephanie L.; Adachi, Kristina; Cherry, James D.; Xu, Zhiheng; Cheng, Genhong; Moreira, Maria Elisabeth Lopes

doi:10.1038/s41591-019-0496-1

Cited by 231 publications

(314 citation statements)

References 40 publications

(53 reference statements)

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“…Notably, these data showed that ZIKV proteins were present in the placenta up to delivery, without causing any physical harm to the newborn infant. However, it is important to continue monitoring the newborn as anomalies may manifest at a later time …”

Section: Resultsmentioning

confidence: 99%

Immunological observations and transcriptomic analysis of trimester‐specific full‐term placentas from three Zika virus‐infected women

et al. 2019

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Objectives Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. Methods Full‐term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. Results In this study, each woman exhibited a unique immune response with raised IL‐1RA, IP‐10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co‐localised to placental Hofbauer cells, the placentas showed no anatomic defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centred on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. Conclusion These findings should translate to improve clinical prenatal screening procedures for virus‐infected pregnant patients.

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Section: Resultsmentioning

confidence: 99%

Immunological observations and transcriptomic analysis of trimester‐specific full‐term placentas from three Zika virus‐infected women

et al. 2019

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“…ZIKV infection during pregnancy can result in a range of birth defects that predominantly involve the central nervous system including microcephaly (4)(5)(6). The rate of adverse outcomes varies but can surpass 40% in some regions (7)(8)(9)(10). Similar consequences are observed in macaques, where experimental infection during gestation can lead to fetal neuropathology and demise (11)(12)(13).…”

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confidence: 93%

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Rompay¹,

Coffey²,

Kapoor

et al. 2020

Preprint

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Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmissionand fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV. Significance statement:Zika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.

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Section: Resultsmentioning

confidence: 99%

“…Importantly, fetal development (e.g. blood flow, heart rate, head circumference) should be closely monitored by ultrasound scanning [54] to detect for unwanted anomalies that may surface in the later part of life [25]. Adopting these steps will potentially improve the clinical care administered to affected patients, by identifying potential danger signs associated with ZIKV infection.…”

Section: Discussionmentioning

confidence: 99%

Trimester-specific Zika virus infection affects placental responses in women

Lum

Narang

Hue

et al. 2019

Preprint

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Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children

Cited by 231 publications

References 40 publications

Immunological observations and transcriptomic analysis of trimester‐specific full‐term placentas from three Zika virus‐infected women

Immunological observations and transcriptomic analysis of trimester‐specific full‐term placentas from three Zika virus‐infected women

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Trimester-specific Zika virus infection affects placental responses in women

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