Rapid access to multifunctional molecules was accomplished via a twofold distal C-H functionalization, achieved by the difunctionalization of non-activated alkenes. A modular ruthenium-catalyzed process for the 1,n-difunctionalization (n=67) of nonactivated alkenes is presented, using fluoroalkyl halides and heteroarenes in the reaction. 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. A mechanism, plausible and supported by detailed experimental and computational studies, was put forth.

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). Combining ATG and PT-Cy has been the focus of recent research aimed at further minimizing the risk of graft-versus-host disease. Retrospective transplant data from haploidentical settings suggest that employing PT-Cy together with ATG may correlate with a diminished prevalence of chronic graft-versus-host disease, while not increasing the risk of infection or recurrence when juxtaposed to PT-Cy alone. Reduced PT-Cy doses combined with ATG in haploidentical or unrelated donor situations may serve to diminish the incidence of acute and chronic GvHD, potentially improving survival, specifically GvHD-free, relapse-free survival (GRFS), in comparison to ATG therapy alone. Concerning patients with hematological malignancies who are undergoing allogeneic hematopoietic stem cell transplantation (HSCT), the pairing of PT-Cy and ATG is shown to be a safe and promising therapeutic combination.

The ongoing SARS-CoV-2 pandemic’s spread has been managed, but not ended, by public health measures and vaccination campaigns, predominantly utilizing intramuscular vaccines. Intranasal vaccines can promote the immune response by recruiting and activating mucosal immune cells specifically located in the respiratory epithelium, thereby preventing infection. Our research, using diverse mouse models, encompassing HLA class II-humanized transgenic strains, reports a thorough examination of this concept. 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. Ad5-RBD or Ad5-S administered intramuscularly (i.m.) failed to induce serum or BAL IgA, producing correspondingly lower neutralizing antibody serum titers. Subsequently, pre-existing immunity developed from an intramuscular mRNA vaccination can be vigorously enhanced and re-directed to a mucosal IgA response by intranasal administration. The Ad5-S booster vaccination regimen. Intramuscular (i.m.) routes of administration, but not intranasal (i.n.) routes, yielded Ad5 DNA detection within the liver or spleen. Vaccine vector administration, showing a lack of systemic dissemination, has been correlated with the risk of thrombotic thrombocytopenia. The Ad5-RBD vaccine demonstrated reduced efficacy compared to the Ad5-S vaccine in HLA-DQ8 mice, unlike the equivalent performance in otherwise identical HLA-DQ6 mice, implying that the RBD fragment’s complement of helper-T cell epitopes is insufficient to make it an optimal vaccine antigen. Our preclinical findings, bolstered by our data, offer encouraging support for intranasal SARS-CoV-2 vaccination, suggesting its potential to induce mucosal immunity and thereby potentially prevent SARS-CoV-2 transmission.

The past decade has seen the emergence of camelid nanobodies, enabling novel applications in fields like immuno-imaging, cancer immunotherapy, and the creation of antiviral agents. While these techniques are common, nanobodies are seldom utilized to measure the efficacy of vaccine antigen candidates, which are principally evaluated using monoclonal antibody binding approaches. We present evidence that a nanobody-based ELISA method effectively characterizes the top RSV vaccine candidate, RSVPreF3. In comparison to the well-established antibody AM14, targeting the prefusion form of the RSV surface fusion glycoprotein, RSV F, the nanobody F-VHH-L66 shows a similar performance. The F-VHH-L66 ELISA, besides its other properties, displayed accuracy, linearity, and stability. Subsequently, the binding kinetics of F-VHH-L66 and AM14 to RSVPreF3 are comparable, as confirmed through the use of surface plasmon resonance (SPR). In conclusion, F-VHH-L66’s RSV(A) neutralization capacity matched that of AM14, thereby strengthening its candidacy as a substitute for AM14 in characterizing the pre-fusion structure of RSVPreF3.

Contact tracing data on secondary attack rates can be used to estimate the effectiveness of vaccines in controlling the transmission of SARS-CoV-2 infection. Our analysis focused on estimating the vaccine’s influence on the infectiousness of the index case and the vulnerability of exposed high-risk individuals.

In a multilevel Bayesian regression model, we examined the relationship between RT-PCR test results from the HREC cohort and factors including immunity status (vaccination history, prior infections, and time since last immunity-inducing event), age, sex, the calendar week of the sample collection, household factors, background positivity rate, and dominant circulating variant. The Belgian data collected between January 2021 and January 2022 have been part of the dataset we employed.

Using primary BNT162b2 vaccination, our initial estimates for vaccine effectiveness (VE) are 96% (95% confidence interval 95-97%) against the Alpha variant, 87% (95% confidence interval 84-88%) against the Delta variant, and significantly lower at 31% (95% confidence interval 25-37%) against the Omicron variant. 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. The effectiveness of vaccination against Delta and Omicron variants, measured as the VET-estimate, reduced to 71% (95%CI 64-78) and 55% (95%CI 46-62), respectively, 150 to 200 days after a booster vaccination. Hybrid immunity, which encompassed both vaccination and verifiable previous infection, was strongly associated with a protective effect that was durable and equal to or greater in strength (measured by the number of antigen exposures) against transmission.

Despite the observed variant-specific immune escape, particularly by the Omicron strain, and the subsequent decline in immunity over time following immunization, vaccination remained associated with a reduced risk of SARS-CoV-2 transmission.

Our findings showcased the VOC-specific immune-escape phenomena, notably with Omicron, coupled with a decline in protection post-immunization, however, vaccination was still linked to a lower risk of SARS-CoV-2 transmission.

The Orthobunyavirus genus, specifically the arbovirus Schmallenberg virus (SBV), part of the Peribunyaviridae family, was first detected in Germany in late 2011 and has continued its circulation across Europe, Asia, and Africa. Ruminants infected with this virus develop fever, exhibit fetal malformations, experience decreased milk output, suffer from diarrhea, and experience stillbirths, resulting in economic hardship for agricultural operations of all scales. Previous studies’ success in identifying SBV nucleoprotein (SBV-N) as a promising vaccine candidate guided our investigation into the protein regions potentially responsible for protection. Based on the SBV-N crystal structure, we selectively truncated domains, resulting in the identification of the N-terminal domain (N-term; Met1-Thr133) and a smaller fragment (C4; Met1-Ala58) as vaccine prototypes. Two injections of N-term and C4 polypeptides proved effective in shielding mice deficient in type I interferon (IFN) receptors (IFNAR-/-) from virulent SBV challenge, in sharp contrast to the marked morbidity and weight loss experienced by control groups. Viremia analyses, combined with IFN- secretion from splenocytes re-stimulated with the N-terminal region of the protein, provide evidence that these two parts of SBV-N can serve as subunit vaccines. While both proteinaceous fragments are readily produced in bacterial cultures, the C4 polypeptide exhibits a substantial sequence similarity (87%) to the corresponding region within nucleoproteins of various Simbu serogroup viruses. This serogroup, encompassing Orthobunyaviruses like SBV, also includes veterinary pathogens such as Akabane virus and human-infecting viruses like Oropouche. Subsequently, we hypothesize that this smaller fragment is more advantageous for vaccine nanoparticle formulation, and it initiates subsequent research with other related Orthobunyaviruses.

HIV-positive individuals, not severely immunocompromised and deemed susceptible, are generally advised to receive measles and varicella vaccinations, based on evidence-based guidelines. In spite of this, routine serologic status determinations are not recommended. The seroprevalence of anti-measles and anti-Varicella-Zoster virus (VZV) antibodies was studied in HIV-positive adults who visited Avicenne University Hospital in a Parisian suburb. p38mapk signals Commercial immunoassays were used to analyze sera collected from 268 patients during the years 2018 through 2020. Patients born in Sub-Saharan Africa comprised 55% of the total, a noticeably higher proportion than those of European origin, which made up 23%. A noteworthy seropositivity rate for measles was observed in 914% of patients, while varicella seropositivity was found in 962% of them. One patient out of every ten tested was seronegative for at least one of the diseases. Analysis of individual variables revealed that a younger age (p = 0.0027) was associated with a higher risk of measles seronegativity in the univariate analysis, while shorter time spans since relocating to France (p < 0.0001) and shorter durations since the HIV diagnosis (p = 0.0007) were correlated with an increased risk of VZV seronegativity.