Maternal Immunization of Pregnant Cattle with Recombinant VP8* Protein of Bovine Rotavirus Elicits Neutralizing Antibodies to Multiple Serotypes

1997 ◽  
pp. 405-411 ◽  
Author(s):  
Dongwan Yoo ◽  
Joongbok Lee ◽  
Richard Harland ◽  
Elaine Gibbons ◽  
Youssef Elazhary ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Bovine Rotavirus ◽  
Maternal Immunization

scholarly journals Molecular Characterization of a Subgroup Specificity Associated with the Rotavirus Inner Capsid Protein VP2

2008 ◽  
Vol 82 (6) ◽  
pp. 2752-2764 ◽  
Author(s):  
Sarah M. McDonald ◽  
John T. Patton
Keyword(s):  
Monoclonal Antibody ◽  
Capsid Protein ◽  
Neutralizing Antibodies ◽  
Bovine Rotavirus ◽  
Single Region ◽  
Molecular Determinants ◽  
High Resolution Structure ◽  
Group A Rotaviruses ◽  
Group A

ABSTRACT Group A rotaviruses are classified into serotypes, based on the reactivity pattern of neutralizing antibodies to VP4 and VP7, as well as into subgroups (SGs), based on non-neutralizing antibodies directed against VP6. The inner capsid protein (VP2) has also been described as a SG antigen; however, little is known regarding the molecular determinants of VP2 SG specificity. In this study, we characterize VP2 SGs by correlating genetic markers with the immunoreactivity of the SG-specific monoclonal antibody (YO-60). Our results show that VP2 proteins similar in sequence to that of the prototypic human strain Wa are recognized by YO-60, classifying them as VP2 SG-II. In contrast, proteins not bound by YO-60 are similar to those of human strains DS-1 or AU-1 and represent VP2 SG-I. Using a mutagenesis approach, we identified residues that determine recognition by either YO-60 or the group A-specific VP2 monoclonal antibody (6E8). We found that YO-60 binds to a conformationally dependent epitope that includes Wa VP2 residue M328. The epitope for 6E8 is also contingent upon VP2 conformation and resides within a single region of the protein (Wa VP2 residues A440 to T530). Using a high-resolution structure of bovine rotavirus double-layered particles, we predicted these epitopes to be spatially distinct from each other and located on opposite surfaces of VP2. This study reveals the extent of genetic variation among group A rotavirus VP2 proteins and illuminates the molecular basis for a previously described SG specificity associated with the rotavirus inner capsid protein.

scholarly journals Respiratory Syncytial Virus (RSV) Neutralizing Antibodies at Birth Predict Protection from RSV Illness in Infants in the First 3 Months of Life

2020 ◽  
Author(s):  
Andrea G Buchwald ◽  
Barney S Graham ◽  
Awa Traore ◽  
Fadima Cheick Haidara ◽  
Man Chen ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cord Blood ◽  
Neutralizing Antibodies ◽  
Maternal Immunization ◽  
Young Infants ◽  
Healthy Control ◽  
Antibody Titers ◽  
Syncytial Virus ◽  
Antibody Levels ◽  
Nested Case Control

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of viral pneumonia and bronchiolitis during the first 6 months of life. Placentally transferred antibodies can prevent severe RSV illness, and maternal immunization may reduce illness in young infants. Identification of protective antibody levels facilitates the advancement of vaccine candidates and maternal immunization. Methods We conducted a nested case-control study with 587 Malian mother–infant pairs, followed from birth to age 6 months. RSV cases were infants who developed influenza-like illness (ILI) or pneumonia and were RSV-positive by polymerase chain reaction. Cases were matched to healthy controls and RSV-negative ILI controls. RSV-A and RSV-B neutralizing antibodies were measured in maternal, cord blood, and infant sera at age 3 and 6 months. Results Maternal antibodies were efficiently transferred to infants. Maternal and infant RSV titers were strongly correlated. Infant antibody titers against RSV-A were 3 times higher than those against RSV-B. At birth, infants who remained healthy had significantly higher RSV-A and RSV-B titers compared with infants who subsequently contracted RSV. RSV-A inhibitory concentration (IC)80 titer >239 or RSV-B titer >60 at birth was significantly associated with being a healthy control compared with an RSV case within the first 3 months of life. RSV-A IC80 titers in cord blood were associated with decreased episodes of pneumonia. Conclusions Maternally acquired RSV antibodies were associated with protection of infants against community-detected cases of RSV-ILI and pneumonia. RSV titers in cord blood can predict whether an infant will be infected with RSV or remain uninfected.

scholarly journals Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity

2019 ◽  
Vol 11 (487) ◽  
pp. eaau6039 ◽  
Author(s):  
Chaya D. Patel ◽  
Iara M. Backes ◽  
Sean A. Taylor ◽  
Yike Jiang ◽  
Arnaud Marchant ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
General Concept ◽  
Morbidity And Mortality ◽  
Neonatal Herpes ◽  
Maternal Immunization ◽  
Adult Mice ◽  
Neonatal Herpes Simplex ◽  
Simplex Virus

Neonatal herpes simplex virus (nHSV) infections cause devastating morbidity and mortality in infants. Most nHSV cases are associated with primary maternal infection, consistent with the hypothesis that maternal immunity is protective. In humans, we found HSV-specific neutralizing antibodies in newborns of immune mothers, indicating that placentally transferred HSV-specific antibody is protective. Using a murine model, we showed that passive administration of HSV-specific antibody to dams prevented disseminated infection and mortality in pups. Maternal immunization with an HSV-2 replication-defective vaccine candidate,dl5-29, led to transfer of HSV-specific antibodies into neonatal circulation that protected against nHSV neurological disease and death. Furthermore, we observed considerable anxiety-like behavior in adult mice that had been infected with low doses of HSV as neonates, despite a notable lack of signs of infection. This phenotype suggests that nHSV infection can have an unsuspected and permanent impact on behavior. These behavioral sequelae of nHSV were prevented by maternal immunization withdl5-29, demonstrating an unexpected benefit of immunization. These findings also support the general concept that maternal immunization can prevent neurotropic neonatal infections and associated morbidity and mortality.

scholarly journals Alternative Virus-Like Particle-Associated Prefusion F Proteins as Maternal Vaccines for Respiratory Syncytial Virus

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Jorge C. G. Blanco ◽  
Lurds R. Fernando ◽  
Wei Zhang ◽  
Arash Kamali ◽  
Marina S. Boukhvalova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Young Children ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
F Protein ◽  
Maternal Immunization ◽  
Maternal Vaccination ◽  
Virus Like Particle ◽  
Cotton Rats ◽  
Syncytial Virus

ABSTRACT Maternal vaccination may be the most effective and safest approach to the protection of infants from respiratory syncytial virus (RSV) infection, a severe acute lower respiratory tract disease in infants and young children worldwide. We previously compared five different virus-like particle (VLP)-associated, mutation-stabilized prefusion F (pre-F) proteins, including the prototype DS-Cav1 F VLPs. We showed that alternative versions of prefusion F proteins have different conformations and induce different populations of anti-F protein antibodies. Two of these alternative pre-F VLPs, the UC-2 F and UC-3 F VLPs, stimulated in mice higher titers of neutralizing antibodies than DS-Cav1 F VLPs (M. L. Cullen, R. M. Schmidt, M. G. Torres, A. A. Capoferri, et al., Vaccines 7:21–41, 2019, https://doi.org/10.3390/vaccines7010021). Here we describe a comparison of these two pre-F VLPs with DS-Cav1 F VLPs as maternal vaccines in cotton rats and report that UC-3 F VLPs significantly increased the neutralizing antibody (NAb) titers in pregnant dams compared to DS-Cav1 F VLPs. The neutralizing antibody titers in the sera of the offspring of the dams immunized with UC-3 F VLPs were significantly higher than those in the sera of the offspring of dams immunized with DS-Cav1 VLPs. This increase in serum NAb titers translated to a 6- to 40-fold lower virus titer in the lungs of the RSV-challenged offspring of dams immunized with UC-3 F VLPs than in the lungs of the RSV-challenged offspring of dams immunized with DS-Cav1 F VLPs. Importantly, the offspring of UC-3 F VLP-immunized dams showed significant protection from lung pathology and from induction of inflammatory lung cytokine mRNA expression after RSV challenge. Immunization with UC-3 F VLPs also induced durable levels of high-titer neutralizing antibodies in dams. IMPORTANCE Respiratory syncytial virus (RSV) is a significant human pathogen severely impacting neonates and young children, but no vaccine exists to protect this vulnerable population. Furthermore, direct vaccination of neonates is likely ineffective due to the immaturity of their immune system, and neonate immunization is potentially unsafe. Maternal vaccination may be the best and safest approach to the protection of neonates through the passive transfer of maternal neutralizing antibodies in utero to the fetus after maternal immunization. Here we report that immunization of pregnant cotton rats, a surrogate model for human maternal immunization, with novel RSV virus-like particle (VLP) vaccine candidates containing stabilized prefusion RSV F proteins provides significant levels of protection of the offspring of immunized dams from RSV challenge. We also found that antibodies induced by VLPs containing different versions of the prefusion F protein varied by 40-fold in the extent of protection provided to the offspring of vaccinated dams upon RSV challenge.

scholarly journals Murine Model of Maternal Immunization Demonstrates Protective Role for Antibodies That Mediate Antibody-Dependent Cellular Cytotoxicity in Protecting Neonates From Herpes Simplex Virus Type 1 and Type 2

2019 ◽  
Vol 221 (5) ◽  
pp. 729-738 ◽  
Author(s):  
Carol M Kao ◽  
Jessica Goymer ◽  
Lip Nam Loh ◽  
Aakash Mahant ◽  
Clare Burn Aschner ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Neutralizing Antibodies ◽  
Dominant Role ◽  
Natural Infection ◽  
Significant Protection ◽  
Maternal Immunization ◽  
Dependent Cell ◽  
Simplex Virus ◽  
Hsv 1

Abstract Background Neonatal herpes simplex virus (HSV) disease results in unacceptable morbidity and mortality. The primary humoral immune response to natural infection is neutralizing antibodies (Abs). However, Abs that activate Fc gama receptors (FcγRs) and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) may play a dominant role in protection. In adult mice, a single-cycle HSV candidate vaccine deleted in glycoprotein-D (ΔgD-2) that induces ADCC provided complete protection against HSV disease and prevented the establishment of latency. Passive transfer studies showed that Abs were sufficient for protection. The current study tested the hypothesis that maternal immunization with ΔgD-2 would protect neonates. Methods C57BL/6 female mice were vaccinated 3 weeks apart with ΔgD-2, and pups were challenged at different times postnatally with lethal doses of HSV-1 or HSV-2. Concentration and functionality of Abs and immune cells were assessed. Results Maternal ΔgD-2 immunization provided significant protection and reduced viral dissemination after lethal challenge with HSV-1 or HSV-2. Protection correlated with Abs acquired transplacentally or from breastmilk that mediated ADCC. Protection was reduced when pups were challenged on Day 1 of life, and this was associated with decreased ability of newborn cells to mediate Ab-dependent cell killing. Conclusions Antibodies mediating ADCC provide significant protection against neonatal HSV.

Maternal Immunization Knowledge and Practices Survey

2018 ◽  
Author(s):  
Luz Maria Vilca ◽  
Cristina Martínez ◽  
Miriam Burballa ◽  
Magda Campins
Keyword(s):  
Maternal Immunization

Endothelial Cell Protein S Synthesis Is Upregulated by the Complex of IL-6 and Soluble IL-6 Receptor

1997 ◽  
Vol 77 (05) ◽  
pp. 1014-1019 ◽  
Author(s):  
W Craig Hooper ◽  
Donald J Phillips ◽  
Bruce L Evatt
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Line ◽  
Neutralizing Antibodies ◽  
Hepatoma Cell ◽  
Protein S ◽  
Oncostatin M ◽  
Cell Protein ◽  
Microvascular Endothelial Cell ◽  
Hepatoma Cell Line

SummaryWe have recently demonstrated that the proinflammatory cytokine, interleukin-6 (IL-6), could upregulate the production of protein S in the human hepatoma cell line, HepG-2, but not in endothelial cells. In this study, we have demonstrated that the combination of exogenous IL-6 and soluble IL-6 receptor (sIL-6R) could significantly upregulate protein S production in both primary human umbilical vein endothelial cells (HUVEC) and in the immortalized human microvascular endothelial cell line, HMEC-1. The IL-6/sIL-6R complex was also able to rapidly induce tyrosine phosphorylation of the IL-6 transducer, gpl30. Neutralizing antibodies directed against either IL-6 or gpl30 blocked protein S upregulation by the IL-6/sIL-6R complex. It was also observed that exogenous sIL-6R could also upregulate protein S by forming a complex with IL-6 constitutively produced by the endothelial cell. Two other cytokines which also utilize the gpl30 receptor, oncostatin M (OSM) and leukemia inhibitory factor (LIF), were also able to upregulate endothelial cell protein S. This study demonstrates a mechanism that allows endothelial cells to respond to IL-6 and also illustrates the potential importance of circulating soluble receptors in the regulation of the anticoagulation pathway.

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