scholarly journals No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination

2021 ◽  
Author(s):  
Alice Lu-Culligan ◽  
Alexandra Tabachnikova ◽  
Maria Tokuyama ◽  
Hannah J. Lee ◽  
Carolina Lucas ◽  
...  

AbstractThe impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.

2005 ◽  
Vol 17 (2) ◽  
pp. 319
Author(s):  
K. Kishida ◽  
N. Shibata ◽  
K. Hata ◽  
S. Aoki ◽  
T. Nishisouzu ◽  
...  

Bovine fetal size and fetal heartbeat are important factors for detecting abnormal pregnancies in artificially inseminated and embryo-transferred dairy cows. The purpose of this study was to compare fetal growth and fetal heartbeat by transrectal ultrasonography in the early pregnancy of artificially inseminated (AI) and embryo-transferred (ET) dairy cows. The pregnancies of 86 animals were examined by fetal heartbeat count (n = 35 per animal of AI versus n = 51 per animal of ET) every 5 days from 35 to 60 days after breeding (the day of ovulation = day 0). The pregnancies of 237 animals were measured by fetal crown-rump length (n = 95 per animal of AI versus n = 142 per animal of ET) at 30 days and 60 days after breeding. Built-in electronic calipers were used to measure fetal dimensions on the ultrasonic screen. In addition, the times of first fetal heartbeats were recorded. Data were analyzed using ANOVA. The results are presented in the Table (Values were mean ± SD except for No. of animals). There were no differences in the range of fetal heartbeat for AI and ET (161.0 to 185.3 beats min−1 versus 169.7 to 184.6 beats min−1). However, fetal heartbeats of AI at 35 days of gestation was higher (P < 0.05) than those in cows at days 40, 45, 50, 55 and 60 of gestation (185.3 ± 8.7 beats min−1 versus 161.0 ± 9.5, 165.0 ± 19.5, 170.3 ± 26.8, 169.4 ± 27.8, and 171.2 ± 11.9 beats min−1, respectively). There were no differences in fetal crown-rump length between AI and ET. The prediction equation for crown-rump length in relation to fetal age of AI was y = 0.0046x2 − 0.2452x + 4.4424, R2 = 0.9643, while that for ET was y = 0.0049x2 − 0.2699x + 4.9396, R2 = 0.9728. Crown-rump length at 30 days and 60 days of gestation did not differ between AI and ET (1.2 ± 0.1 cm versus 1.2 ± 0.1 cm, 6.4 ± 0.3 cm versus 6.5 ± 0.4 cm, respectively). In conclusion, there were no differences in fetal development and heartbeats between AI and ET dairy cows. In addition, there were no differences in fetal crown-rump length between AI and ET dairy cows. Table 1. Comparison of fetal development and heartbeat by ultrasonography in AI and ET dairy cows


2020 ◽  
Vol 7 ◽  
Author(s):  
Haley E. Rymut ◽  
Courtni R. Bolt ◽  
Megan P. Caputo ◽  
Alexandra K. Houser ◽  
Adrienne M. Antonson ◽  
...  

The combined effects on pig behavior of maternal immune challenge during gestation followed by a second immune challenge later in life have not been studied. Porcine reproductive and respiratory syndrome virus (PRRSV) infection during gestation can elicit maternal immune activation (MIA) yet the interactions with the offspring response to a second immune challenge after birth remains unexplored. Knowledge on the response to viral challenges in rodents has been gained through the use of the viral mimetic polyinosinic-polycytidylic acid (Poly(I:C)), yet the effects of this immune stimulant on pig behavior have not been assessed. This study advances the understanding of the combined effect of MIA and a second immune challenge later in life on female and male pig behavior. Three complementary experiments enabled the development of an effective Poly(I:C) challenge in pigs, and testing the interaction between PRRSV-elicited MIA, Poly(I:C) challenge at 60 days of age, and sex on behaviors. Individual-level observations on sickness, locomotor, and social behaviors were measured 1–3 h after Poly(I:C) challenge. Vomiting, panting, lethargy, walking, laying, playing, and touching behaviors were analyzed using generalized linear mixed effect models. Results indicated that a Poly(I:C) dose of 1 mg/kg within 1 h after injection increased the incidence of laying and sickness behavior. The Poly(I:C) challenge decreased the incidence of locomotor behaviors and activity levels. Pigs exposed to MIA had lower rates of social behaviors such as playing. The combined effect of PRRSV-elicited MIA and Poly(I:C) immune challenge further sensitized the pigs to behavior disruption across sexes including changes in sternal and lateral laying, walking, lethargy, and touching incidence. Notably, the effects of Poly(I:C) immune challenge alone on behaviors tended to be more extreme in males, whereas the effects of Poly(I:C) following MIA tended to be more extreme in females. Our findings demonstrate that MIA and Poly(I:C) affected behaviors, and the viral mimetic effects shortly after injection can offer insights into the prolonged effect of postnatal viral infections on feeding, social interactions and health status. Management practices that reduce the likelihood of gestational diseases and accommodate for behavioral disruptions in the offspring can minimize the impact of MIA.


Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1299
Author(s):  
Julie A. Hicks ◽  
Dongwan Yoo ◽  
Hsiao-Ching Liu

Porcine Reproductive and Respiratory Syndrome (PRRS) is a contagious viral (PRRSV) disease in pigs characterized by poor reproductive health, increased mortality, and reductions in growth rates. PRRSV is known to implement immuno-antagonistic mechanisms to evade detection and mute host responses to infection. To better understand the cellular immunosignature of PRRSV we have undertaken transcriptome and immunomodulatory studies in PRRSV-infected porcine alveolar macrophages (PAMs). We first used genome-wide transcriptome profiling (RNA-seq) to elucidate PRRSV-induced changes in the PAM transcriptome in response to infection. We found a number of cellular networks were altered by PRRSV infection, including many associated with innate immunity, such as, the NLRP3 inflammasome. To further explore the role(s) of innate immune networks in PRRSV-infected PAMs, we used an NLRP3-specific inhibitor, MCC950, to identify the potential functionality of the inflammasome during PRRSV replication. We found that PRRSV does quickly induce expression of inflammasome-associated genes in PAMs. Treatment of PAMs with MCC950 suggests NLRP3 inflammasome activation negatively impacts viral replication. Treatment of PAMs with cell culture supernatants from macrophages subjected to NLRP3 inflammasome activation (via polyinosinic-polycytidylic acid (poly I:C) transfection), prior to PRRSV infection resulted in significantly reduced viral RNA levels compared to PAMs treated with cell culture supernatants from macrophages subjected to NLRP3 inflammasome inhibition (MCC950 treatment/poly I:C transfection). This further supports a role for NLRP3 inflammasome activation in the innate macrophagic anti-PRRSV immune response and suggests that PRRSV is sensitive to the effects of NLRP3 inflammasome activity. Taken together, these transcriptome and immunoregulatory data highlight the complex changes PRRSV infection induces in the molecular immune networks of its cellular host.


2021 ◽  
Vol 11 (3) ◽  
pp. 344
Author(s):  
Kinga Gzielo ◽  
Agnieszka Potasiewicz ◽  
Ewa Litwa ◽  
Diana Piotrowska ◽  
Piotr Popik ◽  
...  

Prenatal maternal infection is associated with an increased risk of various neurodevelopmental disorders, including autism spectrum disorders (ASD). Maternal immune activation (MIA) can be experimentally induced by prenatal administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic viral-like double-stranded RNA. Although this MIA model is adopted in many studies, social and communicative deficits, included in the first diagnostic criterion of ASD, are poorly described in the offspring of poly(I:C)-exposed dams. This study aimed to characterize the impact of prenatal poly(I:C) exposure on socio-communicative behaviors in adolescent rats. For this purpose, social play behavior was assessed in both males and females. We also analyzed quantitative and structural changes in ultrasonic vocalizations (USVs) emitted by rats during the play test. Deficits of social play behaviors were evident only in male rats. Males also emitted a significantly decreased number of USVs during social encounters. Prenatal poly(I:C) exposure also affected acoustic call parameters, as reflected by the increased peak frequencies. Additionally, repetitive behaviors were demonstrated in autistic-like animals regardless of sex. This study demonstrates that prenatal poly(I:C) exposure impairs socio-communicative functioning in adolescent rats. USVs may be a useful tool for identifying early autistic-like abnormalities.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 530
Author(s):  
Soo Jin Oh ◽  
Ok Sarah Shin

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Overexpression of SARS-CoV-2 N resulted in the attenuation of retinoic acid inducible gene-I (RIG-I)-like receptor-mediated interferon (IFN) production and IFN-induced gene expression. Similar to the SARS-CoV-1 N protein, SARS-CoV-2 N suppressed the interaction between tripartate motif protein 25 (TRIM25) and RIG-I. Furthermore, SARS-CoV-2 N inhibited polyinosinic: polycytidylic acid [poly(I:C)]-mediated IFN signaling at the level of Tank-binding kinase 1 (TBK1) and interfered with the association between TBK1 and interferon regulatory factor 3 (IRF3), subsequently preventing the nuclear translocation of IRF3. We further found that both type I and III IFN production induced by either the influenza virus lacking the nonstructural protein 1 or the Zika virus were suppressed by the SARS-CoV-2 N protein. Our findings provide insights into the molecular function of the SARS-CoV-2 N protein with respect to counteracting the host antiviral immune response.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yang Chen ◽  
Zhengyang Huang ◽  
Bin Wang ◽  
Qinming Yu ◽  
Ran Liu ◽  
...  

Retinoic acid-inducible gene I- (RIG-I-) like receptors (RLRs) have recently been identified as cytoplasmic sensors for viral RNA. RIG-I, a member of RLRs family, plays an important role in innate immunity. Although previous investigations have proved that RIG-I is absent in chickens, it remains largely unknown whether the chicken can respond to RIG-I ligand. In this study, the eukaryotic expression vectors encoding duRIG-I full length (duck RIG-I, containing all domains), duRIG-I N-terminal (containing the two caspase activation and recruitment domain, CARDs), and duRIG-I C-terminal (containing helicase and regulatory domains) labeled with 6*His tags were constructed successfully and detected by western blotting. Luciferase reporter assay and enzyme-linked immunosorbent assay (ELISA) detected the duRIG-I significantly activated NF-κB and induced the expression of IFN-βwhen polyinosinic-polycytidylic acid (poly[I:C], synthetic double-stranded RNA) challenges chicken embryonic fibroblasts cells (DF1 cells), while the duRIG-I was inactive in the absence of poly[I:C]. Further analysis revealed that the CARDs (duRIG-I-N) induced IFN-βproduction regardless of the presence of poly[I:C], while the CARD-lacking duRIG-I (duRIG-I-C) was not capable of activating downstream signals. These results indicate that duRIG-I CARD domain plays an important role in the induction of IFN-βand provide a basis for further studying the function of RIG-I in avian innate immunity.


2009 ◽  
Vol 87 (3) ◽  
pp. 211-220 ◽  
Author(s):  
Nicola Hopwood ◽  
Tlangelani Maswanganyi ◽  
Lois M. Harden

Although it has been established that some acute phase responses present differently depending on whether a virus or bacteria activates the innate immune system, it has not yet been established whether fever and sickness behaviors, such as anorexia and lethargy, present differently. We therefore investigated the effects of administering lipopolysaccharide (LPS) and polyinosinic : polycytidylic acid (poly I:C) on body temperature, food intake, body mass, and activity (cage activity and wheel running). Male Sprague–Dawley rats were randomly assigned to receive an intraperitoneal injection of one of LPS (75 µg/kg or 250 µg/kg), poly I:C (3000 µg/kg or 4000 µg/kg), or saline. Administration of LPS or poly I:C induced fever, anorexia, and lethargy. Although voluntary wheel running and cage activity were both significantly reduced after administration of LPS or poly I:C, they were not affected equally. Indeed voluntary wheel running was decreased on average by approximately 30% more than cage activity regardless of the dose or type of mimetic administered. Our results indicate that poly I:C is less effective at inducing anorexia, lethargy, and fever in rats than is LPS, and that avoidance of exercise in animals and humans during infection is likely to be a more prominent feature of illness than is avoidance of routine daily activity.


2018 ◽  
Vol 46 (9) ◽  
pp. 1048-1056 ◽  
Author(s):  
Joanna Yu ◽  
Christopher Flatley ◽  
Ristan M. Greer ◽  
Sailesh Kumar

Abstract Background: Birth-weight is an important determinant of perinatal outcome with low birth-weight being a particular risk factor for adverse consequences. Aim: To investigate the impact of neonatal sex, mode of birth and gestational age at birth according to birth-weight centile on serious adverse neonatal outcomes in singleton term pregnancies. Materials and methods: This was a retrospective cohort study of singleton term births at the Mater Mother’s Hospital, Brisbane, Australia. Serious adverse neonatal outcome was defined as a composite of severe acidosis at birth (pH ≤7.0 and/or lactate ≥6 mmol/L and/or base excess ≤−12 mmol/L), Apgar <3 at 5 min, neonatal intensive-care unit admission and antepartum or neonatal death. The main exposure variable was birth-weight centile. Results: Of the 69,210 babies in our study, the overall proportion of serious adverse neonatal outcomes was 9.1% (6327/69,210). Overall, neonates in the <3rd birth-weight centile category had the highest adjusted odds ratio (OR) for serious adverse neonatal outcomes [OR 3.53, 95% confidence interval (CI) 3.06–4.07], whilst those in the ≥97th centile group also had elevated odds (OR 1.51, 95% CI 1.30–1.75). Regardless of birth modality, smaller babies in the <3rd centile group had the highest adjusted OR and predicted probability for serious adverse neonatal outcomes. When stratified by sex, male babies consistently demonstrated a higher predicted probability of serious adverse neonatal outcomes across all birth-weight centiles. The adjusted odds, when stratified by gestational age at birth, were the highest from 37+0 to 38+6 weeks in the <3rd centile group (OR 5.97, 95% CI 4.60–7.75). Conclusions: Low and high birth-weights are risk factors for serious adverse neonatal outcomes. The adjusted OR appears to be greatest for babies in the <3rd birth-weight centile group, although an elevated risk was also found in babies within the ≥97th centile category.


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