scholarly journals Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy

2021 ◽  
Author(s):  
Mary Prahl ◽  
Yarden Golan ◽  
Arianna G. Cassidy ◽  
Yusuke Matsui ◽  
Lin Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Placental Transfer ◽  
Maternal Blood ◽  
Early Infancy ◽  
Time Dependent ◽  
Transplacental Transfer ◽  
Protective Antibodies ◽  
Functional Antibodies ◽  
Epitope Binding ◽  
Efficient Transfer

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we found time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persisted during early infancy. Additionally, using phage immunoprecipitation sequencing, we found a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. In conclusion, products of mRNA vaccines are not transferred to the fetus during pregnancy, however timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.

scholarly journals Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy

2021 ◽  
Author(s):  
Mary Prahl ◽  
Yarden Golan ◽  
Arianna Cassidy ◽  
Yusuke Matsui ◽  
Lin Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Placental Transfer ◽  
Maternal Blood ◽  
Early Infancy ◽  
Time Dependent ◽  
Transplacental Transfer ◽  
Protective Antibodies ◽  
Functional Antibodies ◽  
Epitope Binding ◽  
Efficient Transfer

Abstract Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we found time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persisted during early infancy. Additionally, using phage immunoprecipitation sequencing, we found a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. In conclusion, products of mRNA vaccines are not transferred to the fetus during pregnancy, however timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy

Lessons From the E-Ferol Tragedy

PEDIATRICS ◽  
1986 ◽  
Vol 78 (3) ◽  
pp. 503-506
Author(s):  
William F. Balistreri ◽  
Michael K. Farrell ◽  
Kevin E. Bove
Keyword(s):  
Vitamin E ◽  
Placental Transfer ◽  
Serum Vitamin ◽  
Maternal Blood ◽  
Blood Levels ◽  
Antioxidant Vitamin ◽  
Low Birth Weight Infants ◽  
Term Infants ◽  
Naturally Occurring ◽  
Supplemental Vitamin

"Those who cannot remember the past are condemned to repeat it."—G. Sabtatana Several factors combined to suggest that supplemental vitamin E should be administered to low birth weight infants. The persistent concern and controversy, the latter confounded by a paucity of data, have been discussed in recent editorials.1,2 At birh, tissue stores of the naturally occurring lipidsoluble antioxidant vitamin E (α-tocopherol) are low. The amount of total tocopherol in the tissue of premature infants is approximately one half that of full-term infants. 3 Maternal vitamin E supplementation seems to have minimal effect on serum vitamin E levels in the newborn because there is poor placental transfer; maternal blood levels are higher than cord levels.1-3

scholarly journals Structural and molecular basis for foot-and-mouth disease virus neutralization by two potent protective antibodies

2021 ◽  
Author(s):  
Hu Dong ◽  
Pan Liu ◽  
Manyuan Bai ◽  
Kang Wang ◽  
Rui Feng ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Foot And Mouth Disease ◽  
Therapeutic Benefit ◽  
Mouth Disease ◽  
Economic Losses ◽  
Viral Particles ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Protective Antibodies

Outbreaks of Foot-and-mouth disease (FMD) caused by FMD virus result in significant economic losses. Vaccination is helpful, but the benefits are diminished with antigenic diversity within serotypes, instability of the immunogen and inability to confer protection for long durations. Here we have further dissected the mechanisms underpinning the protective efficacy of two previously reported neutralizing antibodies (NAbs), M8 and M170. The atomic details of the epitopes of M8 and M170 unveiled suggest that protection is conferred by disrupting the virus-receptor interactions. Consequently, administration of these NAbs conferred prophylactic and therapeutic benefit in guinea pigs, raising the possibility of administering NAbs before or during vaccination to confer immediate protection; well before the bolstering of the immune response by the vaccine. Differences in the residues and the conformation of elements making up the epitopes explain the differences in specificities of M8 and M170. An ability to bind 146S viral particles specifically, but not 12S degraded components, highlights a likely role for M170 in the quality control of vaccines.

scholarly journals Biomaterials and oxygen join forces to shape the immune response and boost SARS-CoV-2 vaccines

2020 ◽  
Author(s):  
Thibault Colombani ◽  
Loek Eggermont ◽  
Zachary Rogers ◽  
Lindsay McKay ◽  
Laura Avena ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Full Potential ◽  
Protein Subunit ◽  
Subunit Vaccines ◽  
Health Crisis ◽  
Th2 Immune Response ◽  
Protective Antibodies ◽  
Advanced Biomaterials

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global health crisis, resulting in a critical need for effective vaccines that generate protective antibodies. Protein subunit vaccines represent a promising approach but often lack the immunogenicity required for strong immune stimulation. To overcome this challenge, we first demonstrate that advanced biomaterials boost effectiveness of SARS-CoV-2 protein subunit vaccines. Additionally, we report that oxygen is a powerful immunological co-adjuvant, a game-changer in the field for unlocking the full potential of vaccines. Mice immunized with oxygen-generating cryogel vaccines exhibited a robust and balanced Th1 and Th2 immune response, leading to sustained and high titer production of neutralizing antibodies against SARS-CoV-2. Our data indicate that this platform is a revolutionary technology with the potential to reinforce any vaccine.

Phenoxybenzameve Placental Transfer during the Third Trimester

1996 ◽  
Vol 30 (11) ◽  
pp. 1249-1251 ◽  
Author(s):  
Maria L Santeiro ◽  
Carine Stromquist ◽  
Lance Wyble
Keyword(s):  
Amniotic Fluid ◽  
Perinatal Depression ◽  
Placental Transfer ◽  
Male Infant ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
Third Trimester ◽  
Days Of Therapy ◽  
Maternal Hypertension ◽  
Placental Passage

OBJECTIVE: To report phenoxybenzamine placental transfer in the treatment of maternal hypertension secondary to pheochromocytoma. CASE SUMMARY: A 22-year-old woman diagnosed with pheochromocytoma was medically managed at 33 weeks gestation with oral phenoxybenzamine and labetalol until delivery 26 days later. To determine phenoxybenzamine placental passage, at the time of cesarean section simultaneous samples were obtained from the cord blood, maternal blood, and amniotic fluid. Additional blood samples were obtained from the newborn at 32 and 80 hours of life. Mean concentrations of phenoxybenzamine from cord and maternal plasma and in amniotic fluid were 103.3,66, and 79.3 ng/mL, respectively; the newborn's plasma concentration at 32 hours of life was 22.3 ng/mL. At the time of delivery, the 2475-g male infant exhibited perinatal depression; mild transient hypotension was also noted for the first few days of life. DISCUSSION: The fetal—maternal plasma accumulation ratio of 1.6:1 indicates that at this gestational age after 26 days of therapy, the placental transfer of phenoxybenzamine occurs and is accompanied by accumulation in the fetal blood. CONCLUSIONS: Because of the placental transfer of phenoxybenzamine, mild perinatal depression and transient hypotension may occur in newborns of mothers receiving this medication. These newborns must be closely monitored during the first few days of life for respiratory depression and hypotension.

scholarly journals Multifunctional Antibodies Are Induced by the RTS,S Malaria Vaccine and Associated With Protection in a Phase 1/2a Trial

2020 ◽  
Author(s):  
Liriye Kurtovic ◽  
Tanmaya Atre ◽  
Gaoqian Feng ◽  
Bruce D Wines ◽  
Jo-Anne Chan ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Protective Efficacy ◽  
Phase 1 ◽  
Vaccine Dose ◽  
Effector Functions ◽  
Malaria Vaccines ◽  
Multiple Regions ◽  
Protective Antibodies ◽  
Falciparum Sporozoite ◽  
Functional Antibodies

Abstract Background RTS,S is the leading malaria vaccine candidate but only confers partial efficacy against malaria in children. RTS,S is based on the major Plasmodium falciparum sporozoite surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is important for protection; however, it is unclear how these protective antibodies function. Methods We quantified the induction of functional anti-CSP antibody responses in healthy malaria-naive adults (N = 45) vaccinated with RTS,S/AS01. This included the ability to mediate effector functions via the fragment crystallizable (Fc) region, such as interacting with human complement proteins and Fcγ-receptors (FcγRs) that are expressed on immune cells, which promote various immunological functions. Results Our major findings were (1) RTS,S-induced antibodies mediated Fc-dependent effector functions, (2) functional antibodies were generally highest after the second vaccine dose, (3) functional antibodies targeted multiple regions of CSP, (4) participants with higher levels of functional antibodies had a reduced probability of developing parasitemia following homologous challenge (P < .05), and (5) nonprotected subjects had higher levels of anti-CSP IgM. Conclusions Our data suggest a role for Fc-dependent antibody effector functions in RTS,S-induced immunity. Enhancing the induction of these functional activities may be a strategy to improve the protective efficacy of RTS,S or other malaria vaccines. Clinical Trials Registration NCT00075049

scholarly journals Oligomeric state of the ZIKV E protein defines protective immune responses

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Stefan W. Metz ◽  
Ashlie Thomas ◽  
Alex Brackbill ◽  
John Forsberg ◽  
Michael J. Miley ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Quaternary Structure ◽  
Poor Performance ◽  
Oligomeric State ◽  
Subunit Vaccines ◽  
Safety Issues ◽  
E Protein ◽  
Protective Antibodies ◽  
Low Levels ◽  
Domain Iii

Abstract The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines.

scholarly journals Transplacental Uptake of Glucose Is Decreased in Embryonic Lethal Connexin26-deficient Mice

1998 ◽  
Vol 140 (6) ◽  
pp. 1453-1461 ◽  
Author(s):  
Heinz-Dieter Gabriel ◽  
Dirk Jung ◽  
Christoph Bützler ◽  
Achim Temme ◽  
Otto Traub ◽  
...  
Keyword(s):  
Placental Transfer ◽  
Maternal Blood ◽  
Wild Type ◽  
Waste Products ◽  
Morphological Alterations ◽  
Gene Coding ◽  
Junctional Protein ◽  
Chorioallantoic Placenta ◽  
Gap Junctional ◽  
Glucose Analogue

Mice that harbor a targeted homozygous defect in the gene coding for the gap junctional protein connexin26 died in utero during the transient phase from early to midgestation. From day 10 post coitum onwards, development of homozygous embryos was retarded, which led to death around day 11 post coitum. Except for growth retardation, no gross morphological alterations were detected between homozygous connexin26-defective embryos and wild-type littermates. At day 9 postcoitum, when chorioallantoic placenta started to function, connexin26 was weakly expressed in the yolk sac epithelium, between syncytiotrophoblasts I and II in the labyrinth region of the placenta, and in the skin of the embryo. At day 10 post coitum, expression of connexin26 in the placenta was much stronger than at the other locations. To analyze involvement of connexin26 in the placental transfer of nutrients, we have measured embryonic uptake of the nonmetabolizable glucose analogue 3-O-[14C]methylglucose, injected into the maternal tail vein. At day 10 post coitum, viable, homozygous connexin26-defective embryos accumulated only ∼40% of the radioactivity measured in wild-type and heterozygous littermates of the same size. We conclude that the uptake of glucose, and presumably other nutrients as well, from maternal blood into connexin26-deficient mouse embryos was severely impaired and apparently not sufficient to support the rapid organogenesis during midgestation. Our results suggest that connexin26 gap junction channels likely fulfill an essential role in the transfer of maternal nutrients and embryonic waste products between syncytiotrophoblast I and II in the labyrinth layer of the mouse placenta.

scholarly journals Ablation of the Complementarity-Determining Region H3 Apex of the Anti-HIV-1 Broadly Neutralizing Antibody 2F5 Abrogates Neutralizing Capacity without Affecting Core Epitope Binding

2010 ◽  
Vol 84 (9) ◽  
pp. 4136-4147 ◽  
Author(s):  
Jean-Philippe Julien ◽  
Nerea Huarte ◽  
Rubén Maeso ◽  
Stefka G. Taneva ◽  
Annie Cunningham ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Hydrophobic Interactions ◽  
Neutralizing Antibody ◽  
Titration Calorimetry ◽  
Peptide Epitope ◽  
Neutralizing Capacity ◽  
Epitope Binding ◽  
Hiv 1 ◽  
Complementarity Determining Region

ABSTRACT The identification and characterization of broadly neutralizing antibodies (bnAbs) against HIV-1 has formed a major research focus, with the ultimate goal to help in the design of an effective AIDS vaccine. One of these bnAbs, 2F5, has been extensively characterized, and residues at the apex of its unusually long complementarity-determining region (CDR) H3 loop have been shown to be crucial for neutralization. Structural studies, however, have revealed that the 100TLFGVPI100F apex residues of the CDR H3 loop do not interact directly with residues of its core gp41 epitope. In an attempt to gain better insight into the functional role of this element, we have recombinantly expressed native 2F5 Fab and two mutants in which either the apical Phe100B(H) residue was changed to an alanine or the CDR H3 residues 100TLFGVPI100F were replaced by a Ser-Gly dipeptide linker. Isothermal titration calorimetry (ITC) and competitive-binding enzyme-linked immunosorbent assays (ELISAs) rendered strikingly similar affinity constants (Kd [dissociation constant] of ∼20 nM) for linear peptide epitope binding by 2F5 Fabs, independent of the presence or absence of the apex residues. Ablation of the CDR H3 apex residues, however, abolished the cell-cell fusion inhibition and pseudovirus neutralization capacities of 2F5 Fab. We report competitive ELISA data that suggest a role of 2F5 CDR H3 apex residues in mediating weak hydrophobic interactions with residues located at the C terminus of the gp41 membrane proximal external region and/or membrane components in the context of core epitope binding. The present data therefore imply an extended 2F5 paratope that includes weak secondary interactions that are crucial for neutralization of Env-mediated fusion.

Distribution of relaxin between human maternal and fetal circulations and amniotic fluid

1992 ◽  
Vol 134 (2) ◽  
pp. 313-317 ◽  
Author(s):  
M. R. Johnson ◽  
A. Abbas ◽  
K. H. Nicolaides ◽  
S. L. Lightman
Keyword(s):  
Amniotic Fluid ◽  
Placental Transfer ◽  
Geometric Mean ◽  
Maternal Blood ◽  
Fetal Blood ◽  
Maternal Circulation ◽  
Blood Samples

ABSTRACT Relaxin was measured in maternal blood and amniotic fluid samples at 9–40 weeks and in fetal blood samples at 19–41 weeks of pregnancy. In amniotic fluid, concentrations of relaxin rose from 58 ng/1 (geometric mean) at 10 weeks to 142 ng/l at 14 weeks and declined subsequently to 55 ng/l at 22 weeks. In maternal blood, mean relaxin concentrations were ten times greater than in amniotic fluid, and concentrations decreased with gestation. Since there was no significant association between the relaxin concentrations in the two compartments, relaxin in the amniotic fluid may be derived from the decidualized endometrium rather than the maternal circulation, alternatively its metabolism may be different in the two compartments. The absence of detectable concentrations of relaxin in any of the fetal blood samples demonstrates that there is no significant placental transfer or fetal synthesis of this peptide. Journal of Endocrinology (1992) 134, 313–317

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