Non-activated alkenes underwent difunctionalization, thereby accomplishing a twofold distal C-H functionalization and providing swift access to multifunctionalized molecules. The modular synthesis of 1,n-difunctionalized (n=67) nonactivated alkenes, using fluoroalkyl halides and heteroarenes, is achieved via a ruthenium-catalyzed process. The meta-C(sp2)-H/C-6(sp3)-H distal functionalization displayed remarkably mild conditions, unique selectivity, and broad substrate applicability through a domino process involving twofold remote C(sp2)-H/C(sp3)-H activation, resulting in the sequential formation of three disparate carbon-centered radicals. Experimental and computational work, conducted in detail, led to the proposition of a plausible mechanism.

In the effort to find an ideal partner for conventional immunosuppressive agents, rabbit anti-thymocyte globulin (ATG), and subsequently post-transplant cyclophosphamide (PT-Cy), display valid and efficient efficacy in preventing graft-versus-host disease (GvHD). A strategy combining ATG and PT-Cy has recently been explored as a means to further reduce the risk of graft-versus-host disease. Retrospective analyses in haploidentical transplant recipients suggest that concurrent administration of PT-Cy and ATG could potentially reduce the occurrence of chronic graft-versus-host disease, without exacerbating the risks of infection or recurrence, when compared to PT-Cy therapy alone. When utilizing haploidentical or unrelated donors, the addition of reduced PT-Cy to ATG regimens could potentially decrease the incidence of acute and chronic graft-versus-host disease (GvHD) and improve survival outcomes, notably GvHD-free, relapse-free survival (GRFS), in comparison to ATG alone. For patients with hematological malignancies receiving allogeneic hematopoietic stem cell transplantation (HSCT), the integration of PT-Cy and ATG shows itself as a viable and safe therapeutic strategy.

While public health measures and large-scale vaccination drives, focused on intramuscular vaccines, have brought the SARS-CoV-2 pandemic under control, they have not managed to completely stop its progression. Intranasal vaccines mobilize mucosal immune cells to the respiratory epithelium, enabling their role in infection prevention. This report presents a detailed series of studies on this concept, incorporating various mouse models, including HLA class II-humanized transgenic strains. Intranasal administration of serotype-5 adenoviral vectors expressing either the receptor-binding domain (Ad5-RBD) or the full spike ectodomain (Ad5-S) of SARS-CoV-2, proved effective in i) inducing serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) generating robust SARS-CoV-2 neutralizing activity in both serum and BAL, iii) stimulating a vigorous spike-directed T helper 1 and cytotoxic T cell immune response, and iv) protecting mice from infection with the SARS-CoV-2 beta variant. By means of intramuscular (i.m.) administration, Ad5-RBD or Ad5-S administration failed to induce serum or BAL IgA and produced lower serum neutralizing antibody titers. Importantly, the immunity prompted by an intramuscular mRNA vaccination can be powerfully bolstered and reoriented to a mucosal IgA response through an intranasal approach. An Ad5-S booster vaccination. Interestingly, the liver or spleen exhibited the presence of Ad5 DNA after intramuscular (i.m.) administration, whereas intranasal (i.n.) administration did not. Vaccine vector administration, showing a lack of systemic dissemination, has been correlated with the risk of thrombotic thrombocytopenia. While HLA-DQ6 mice showed no significant difference between the efficacy of Ad5-RBD and Ad5-S vaccines, the Ad5-RBD vaccine was less effective than the Ad5-S vaccine in HLA-DQ8 mice, suggesting that the RBD fragment alone is insufficient in providing a complete set of helper-T cell epitopes for an optimal vaccine. Our research, building upon earlier promising preclinical work on intranasal SARS-CoV-2 vaccination, corroborates the potential of this approach to stimulate mucosal immunity, thereby potentially decreasing the transmission of SARS-CoV-2.

In the last ten years, camelid nanobodies have been successfully adapted for diverse applications, including the utilization of immuno-imaging techniques, cancer immunotherapy strategies, and antiviral medication development. Even though these methodologies are prevalent, nanobodies are used quite infrequently to determine the strength of vaccine antigen candidates, which are typically tested via monoclonal antibody binding methods. Using an ELISA method based on nanobodies, we find it suitable for the characterization of the leading RSV vaccine candidate, RSVPreF3. The nanobody F-VHH-L66, like the well-known antibody AM14 targeting the prefusion form of RSV F, the RSV surface fusion glycoprotein, displays similar characteristics. Analysis of the F-VHH-L66 ELISA showed accurate, linear results and indicated the stability of the assay. Likewise, the binding kinetics of F-VHH-L66 to RSVPreF3 are comparable to those of AM14, when employing surface plasmon resonance (SPR) technology. In the final analysis, F-VHH-L66’s neutralization of RSV(A) demonstrated comparable efficacy to AM14, supporting its potential as a substitute for AM14 in the structural analysis of the RSVPreF3 pre-fusion form.

One can ascertain vaccine efficacy in stopping the spread of SARS-CoV-2 by evaluating the secondary attack rates that are observed through contact tracing. We assessed the vaccine’s impact on the contagiousness of the initial case and the susceptibility of high-risk contacts.

A multilevel Bayesian regression model was used to examine the correlation between RT-PCR test results from the HREC cohort and a range of factors, namely, immunity status (vaccination history, prior infection, time since last immunity-boosting event), age, sex, calendar week of sample collection, household environment, background positivity rate, and dominant viral variant. The Belgian data collected between January 2021 and January 2022 have been part of the dataset we employed.

Regarding primary BNT162b2 vaccination, our initial estimates of vaccine efficacy (VE) demonstrate 96% (95% confidence interval 95-97%) protection against Alpha, 87% (95% confidence interval 84-88%) against Delta, and a substantially reduced 31% (95% confidence interval 25-37%) against Omicron. Initial vaccination efficacy for booster shots (mRNA primary and booster) stood at 87% (95% confidence interval 86-89) against the Delta variant, and a lower 68% (95% confidence interval 65-70) against the Omicron variant. Following booster vaccination, the VET-estimate for Delta and Omicron variants decreased to 71% (95%CI 64-78) and 55% (95%CI 46-62), respectively, between 150 and 200 days later. Hybrid immunity, a status defined by vaccination along with documented prior infection, was correlated with a protective effect that was sustained and identical or superior (by assessing the number of antigen exposures) against transmission.

Even with the documented VOC-specific immune escape, particularly in the Omicron lineage, and the observed decrease in immunity following immunization, vaccination still showed a connection to a lower risk of SARS-CoV-2 transmission.

Vaccination, despite the observed waning immunity, particularly against Omicron variants of concern (VOCs), and VOC-specific immune escape, was still associated with a reduced likelihood of SARS-CoV-2 transmission.

The Schmallenberg virus (SBV), an arbovirus belonging to the Peribunyaviridae family and the Orthobunyavirus genus, was first identified in Germany during late 2011 and has since circulated throughout Europe, Asia, and Africa. A disease impacting ruminants, caused by a virus, includes symptoms such as fever, fetal deformities, diminished milk production, diarrhea, and stillbirths, causing financial problems for small and large farms alike. Prior research indicating SBV nucleoprotein (SBV-N) as a promising vaccine candidate spurred our study to identify the protein regions correlating with protection. By strategically truncating domains based on the SBV-N crystal structure, we were able to pinpoint the N-terminal domain (N-term; Met1-Thr133) and a smaller segment (C4; Met1-Ala58) as vaccine prototypes. In contrast to control groups that exhibited severe morbidity and weight loss following virulent SBV challenge, mice deficient in type I interferon (IFN) receptors (IFNAR-/-) receiving two injections of N-term and C4 polypeptides were shielded from the pathogen’s effects. The findings from viremia analyses, along with IFN- production from splenocytes re-stimulated using the N-terminal portion of the protein, support the potential of these two SBV-N segments as subunit vaccines. In bacterial cells, both proteinaceous fragments are readily synthesized. The C4 polypeptide displays a significant sequence homology (87%) with the equivalent portion of nucleoproteins in several viruses of the Simbu serogroup, a group containing SBV, veterinary pathogens such as Akabane virus, and human-infecting viruses, including Oropouche virus. In view of this, we propose that this smaller segment is more suitable for the creation of vaccine nanoparticles, and this consequently facilitates further research into other related Orthobunyaviruses.

Measles and varicella vaccines are typically recommended for susceptible HIV-positive patients, barring severe immunocompromise, in alignment with evidence-based guidelines. Even though it is routine, a serologic status screening is not recommended. An investigation into the seroprevalence of anti-measles and anti-Varicella-Zoster virus (VZV) antibodies was undertaken among HIV-positive adults at Avicenne University Hospital, located in a Parisian suburb. mnk signal Patient sera, collected in the period from 2018 to 2020, underwent evaluation using commercial immunoassay techniques on 268 individuals. The distribution of birthplace among patients showed a prevalence of Sub-Saharan Africa (55%), notably greater than the 23% who were from Europe. Of the patients, 914% exhibited measles seropositivity and 962% exhibited varicella seropositivity. A tenth of the patients displayed seronegativity to one or more of the diseases that were tested. Younger age (p = 0.0027) emerged as the sole factor associated with an elevated risk of measles seronegativity in the univariate analysis, while shorter periods since arrival in France (p < 0.0001) and since HIV diagnosis (p = 0.0007) were significantly linked to a higher risk of VZV seronegativity.