Immunogenicity Following Administration of BNT162b2 and Ad26.COV2.S COVID-19 Vaccines in the Pregnant Population during the Third Trimester

Globally, COVID-19 vaccines are currently being used to prevent transmission and to reduce morbidity and death associated with SARS-CoV-2 infection. Current research reveals that vaccines such as BNT162b2 and Ad26.COV2.S are highly immunogenic and have high short-term effectiveness for most of the known viral variants. Clinical trials showed satisfying results in the general population, but the reluctance in testing and vaccinating pregnant women left this category with little evidence regarding the safety, efficacy, and immunogenicity following COVID-19 vaccination. With the worldwide incidence of COVID-19 remaining high and the possibility of new transmissible SARS-CoV-2 mutations, data on vaccination effectiveness and antibody dynamics in pregnant patients are critical for determining the need for special care or further booster doses. An observational study was developed to evaluate pregnant women receiving the complete COVID-19 vaccination scheme using the BNT162b2 and Ad26.COV2.S, and determine pregnancy-related outcomes in the mothers and their newborns, as well as determining adverse events after vaccination and immunogenicity of vaccines during four months. There were no abnormal findings in pregnancy and newborn characteristics comparing vaccinated versus unvaccinated pregnant women. COVID-19 seropositive pregnant women had significantly higher spike antibody titers than seronegative patients with similar characteristics, although they were more likely to develop fever and lymphadenopathy following vaccination. The same group of pregnant women showed no statistically significant differences in antibody titers during a 4-month period when compared with case-matched non-pregnant women. The BNT162b2 and Ad26.COV2.S vaccines are safe to administer during the third trimester of pregnancy, while their safety, efficacy, and immunogenicity remain similar to those of the general population.     

Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non‐chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation ( http://www.clinicaltrials.gov # NCT00675038).     

Spatial and temporal differences in the blood parasite fauna of passerine birds during the spring migration in Bulgaria

Species composition and prevalence of the blood parasites of three migratory Acrocephalus species of warblers (Acrocephalus arundinaceus, Acrocephalus scirpaceus and Acrocephalus schoenobaenus) were studied during spring period in Bulgaria. For each of the studied species, we compared the parasite fauna during their spring migration at three study sites in search of infection patterns in time and space. Spatial differences were registered in the blood parasites and their prevalence for two of the studied species—A. arundinaceus and A. scirpaceus, whereas for the third one—A. schoenobaenus, there were no significant differences. The parasite species Haemoproteus belopolskyi was present in migrating A. arundinaceus only at Kalimok station, but not at the other two sampling locations. Plasmodium prevalence in A. arundinaceus migrating through Kalimok was also different between years. A decrease of H. belopolskyi prevalence was detected for A. schoenobaenus at Petarch during the spring of 2006. On the contrary, Plasmodium (Haemamoeba) sp. infections of the same bird species increased during the spring period. The differences found between sites could be explained with the different origin of the migrants at different migration stopover points. Climatic conditions and vector abundance in the zones of origin are probable reasons for the observed differences between years.     

Contrast-Enhanced Ultrasound Defines Vascularization Pattern of Hamartomatous Colonic Polyps in Peutz-Jeghers Syndrome

The hamartomatous polyps in Peutz-Jeghers syndrome may have malignant potential. To differentiate between hamartomatous and adenomas polyps, vascular characterization can be assessed using noninvasive procedures, such as contrast-enhanced ultrasound (CEUS). The neo-angiogenic characteristics of colorectal adenomas and carcinomas are expressed as an anarchic vascular pattern observed on CEUS. Using CEUS in a patient with Peutz-Jeghers syndrome, we describe for the first time the vascularization of a hamartomatous colonic polyp that exhibits a hierarchy branching pattern.     

Impaired salivary gland activity in patients with autoimmune polyendocrine syndrome type I

Autoimmune polyendocrine syndrome type I (APS-I) is a severe disease caused by mutations in the autoimmune regulator (AIRE) gene. We hypothesized that salivary gland dysfunction could be a possible unexplored component of these patients and here aimed to investigate salivary and lachrymal symptoms in the Norwegian cohort of APS-I patients (N?=?41) and the aetiology behind it. Sicca symptoms and possible corresponding underlying factors were assessed by subjective reports combined with objective measures of saliva and tear flow, serological testing, immune fluorescence microscopy, ultrasonography and searching for putative autoantibodies in the salivary glands. In addition, defensin and anti-defensin levels were analysed in patients and compared with healthy controls. Our results indicate mild salivary and/or lachrymal gland dysfunction manifesting in low saliva or tear flow in a total of 62% of APS-I patients. Serum IgG from 9 of 12 patients bound to targets in salivary gland biopsy slides, although the specificity and pattern of binding varied. There was no reactivity against known Sjögren-associated autoantigens in sera from APS-I patients using quantitative methods, but 11% were ANA positive by immunofluorescence microscopy. We identified several putative autoantigens in one patient, although none of these were verified as APS-I specific. We conclude that impaired salivary gland activity is part of the clinical picture of APS-I and our findings could indicate an autoimmune aetiology. We further show that APS-I patients have an altered antimicrobial signature in both sera and saliva, which requires further investigations.     

New pansomatostatin ligands and their chelated versions: affinity profile, agonist activity, internalization, and tumor targeting.

PURPOSE: Somatostatin receptor (sst) targeting is an established method to image and treat sst-positive tumors. Particularly, neuroendocrine tumors express the receptor subtype 2 in high density, but sst1, sst3, sst4, and sst5 are also expressed to some extent in different human tumors. Currently used targeting peptides mainly have sst2 affinity. We aimed at developing (radio)peptides that bind with high affinity to all receptor subtypes. EXPERIMENTAL DESIGN: Carbocyclic octapeptides were coupled with macrocyclic chelators for radiometal labeling. Affinity, internalization, and agonist potencies were determined on sst1- to sst5-expressing cell lines. Biodistribution was determined on nude mice bearing HEK-sst2 or AR4-2J and HEK-sst3 tumors. RESULTS: High affinity to all receptor subtypes was found. Y(III)-KE88 showed agonistic properties at all five sst receptor subtypes as it inhibits forskolin-stimulated cyclic AMP production. Surprisingly, very low or even absent sst2 receptor internalization was found compared with currently clinically established octapeptides, whereas the sst3 internalization was very efficient. Biodistribution studies of [(111)In]KE88 and [(67)Ga]KE88/[(68)Ga]KE88 reflected the in vitro data. In nude mice with s.c. implanted sst2 (HEK-sst2, AR4-2J)-expressing and sst3 (HEK-sst3)-expressing tumors, high and persistent uptake was found in sst3-expressing tumors, whereas the uptake in the sst2-expressing tumors was lower and showed fast washout. The kidney uptake was high but blockable by coinjection of lysine. CONCLUSION: This peptide family shows pansomatostatin potency. As radiopeptides, they are the first to show a full pansomatostatin profile. Despite some drawback, they should be useful for imaging sst2-expressing tumors with short-lived radiometals, such as (68)Ga, at early time points and for sst3-expressing tumors at later time points with longer-lived radiometals, such as (64)Cu or (86)Y.     

Effects of IL-12 on immune responses induced by transcutaneous immunization with antigens formulated in a novel lipid-based biphasic delivery system

The development of non-invasive methods for the delivery of proteins through the permeability barriers, such as the intact skin, will greatly facilitate the administration of human and veterinary vaccines. In the present study we used recombinant Pasteurella haemolytica leukotoxin (Lkt) and hen egg lysozyme (HEL) as model antigens to investigate the ability of transdermal administration of vaccine antigens to induce humoral and cellular responses in mice and to assess the immunomodulatory effects of IL-12 on these antigen-specific immune responses. Mice were immunized by the transdermal route with Lkt or HEL formulated in a novel lipid-based biphasic delivery system (BPDS). Transdermal delivery of Lkt or HEL induced strong polarized Th2 responses characterized by enhancement of antigen-specific IgG1 antibody subclass and predominant induction of antigen specific IL-4 over IFN-gamma in spleen and draining lymph nodes cells. Animals immunized by topical application of formulations containing antigen and IL-12 developed significantly lower antibody titres without significant changes in IL-4 or IFN-gamma secreting cells (SC) in the draining lymph nodes or spleen cells. Our results indicated that application of antigens formulated in BPDS induced antigen-specific immune responses. Furthermore, incorporation of IL-12 to the vaccine formulation influences the induction of antibody responses induced by transdermal immunization. We demonstrated the feasibility of using this technology for the development of non-invasive methods of vaccine administration.     

Secondary transplantation following a period of isografting: experimental study in rats

The authors describe a study in which groin flaps from 20 Wistar rats were transplanted to another group of 20 Wistar rats and, after various time intervals, the groin flaps were re-transplanted back to the original animals. The goal of the first transfers was to preserve the flap in the second group of animals (isopreservation). During the isopreservation period, the second rat (the preserver) was treated with steroids or FK506 for immunosuppression. Thirty-three free groin flap transfers were performed between 40 rats. If possible, the same flap was transferred twice between two animals, one as an isograft, and other as an autograft following an isopreservation period in 13 pairs of animals. (A second transfer was not possible in seven pairs of animals.) The period for isopreservation varied between 2 days and 1 week. The survival of the flap was observed by visual inspection, laser Doppler flowmeter measurements, and was correlated with serial histopathologic examinations of skin and vessel biopsy specimens, including the anastomosis site. The severity of histopathologic signs that might be related to developing rejection was increased by the preservation time, and was more noticeable after the second transfer. The authors showed that successful secondary transplantation of the rat groin flap with a 1-week follow-up could be achieved, following isopreservation of at least up to 5 days.