Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with unknown etiology and no effective treatment. In this study, we show that primary cultures of fibroblasts derived from lung biopsies of IPF patients exhibited (i) accelerated replicative cellular senescence (CS); (ii) high resistance to oxidative-stress-induced cytotoxicity or CS; (iii) a CS-like morphology (even at the proliferative phase); and (iv) rapid accumulation of senescent cells expressing the myofibroblast marker α-SMA. Our findings suggest that CS could serve as a bridge connecting lung aging and its quite frequent outcome -- pulmonary fibrosis, and be an important player in the disease progression. Consequently, targeting senescent cells offers the potential of being a promising therapeutic approach.     

A novel anchoring system for colonic stents: a pilot in vivo study in a porcine model

Background

Colorectal stents have a proven role in colorectal cancer as palliative care or a bridge to surgery. However, their efficacy and anchoring to the tissue varies according to stent design with stent migration rates up to 50 %. We present preliminary in vivo results of a new end-luminal anchoring system for stent fixation to the rectal canal. The aim was to assess the efficacy and safety of the stent using the anchoring system while subjecting the device to daily abdominal pressures related to daily activities in a porcine animal model.

Methods

Ex vivo anatomical and physical studies were performed to improve the system’s structure and safety. Four female pigs were followed for the acute and chronic (16 weeks) period. Two animals were euthanized and underwent en-bloc pelvic visceral excision and histopathological examination. Device fixation time, animal behavior, device patency, anoscopic examination and histopathological features were assessed.

Results

Mean anchoring time was 13.83 weeks (standard error ± 1.38 weeks). One of the animals experienced early device expulsion with no complications. No obstruction was noted in any of the animals. Macroscopic examination revealed mild focal submucosal scarring in one animal and a normal examination in the other. Hematoxylin and eosin staining revealed mucosal ulceration and mixed inflammatory cell infiltrate, with no signs of granulomata, foreign body giant cell reaction or microabscess formation.

Conclusions

A novel fixation device designed for long-term intrarectal implantation was well tolerated and maintained anal canal patency without migration. Larger studies are needed before its implementation in humans.     

Glucose metabolism: key endogenous regulator of β-cell replication and survival

Recent studies in mice have shown that pancreatic β-cells have a significant potential for regeneration, suggesting that regenerative therapy for diabetes is feasible. Genetic lineage tracing studies indicate that β-cell regeneration is based on the replication of fully differentiated, insulin-positive β-cells. Thus, a major challenge for this field is to identify and enhance the molecular pathways that control β-cell replication and mass. We review evidence, from human genetics and mouse models, that glucose is a major signal for β-cell replication. The mitogenic effect of blood glucose is transmitted via glucose metabolism within β-cells, and through a signalling cascade that resembles the pathway for glucose-stimulated insulin secretion. We introduce the concept that the individual β-cell workload, defined as the amount of insulin that an individual β-cell must secrete to maintain euglycaemia, is the primary determinant of replication, survival and mass. We also propose that a cell-autonomous pathway, similar to that regulating replication, appears to be responsible for at least some of the toxic effects of glucose on β-cells. Understanding and uncoupling the mitogenic and toxic effects of glucose metabolism on β-cells may allow for the development of effective regenerative therapies for diabetes.