Search Results (77)

Alzheimer’s disease (AD) is one of the most common chronic neurodegenerative disorders worldwide. It is characterized by progressive memory loss and cognitive decline, leading to dementia. The pathogenesis of the disease is primarily attributed to two pathological protein structures: amyloid-beta (Aβ) plaques and tau protein neurofibrils. The current treatment strategies for AD are mainly symptomatic, highlighting the urgent need for the development of new, more effective therapies for the disease. The purpose of this paper is to provide a comprehensive and scientific review of the latest research regarding novel therapeutic options in the treatment of AD. In recent years, research has focused on more advanced and diversified strategies, including immunotherapy, gene therapy, tyrosine kinase inhibitors, therapies targeting mitochondrial function, and neurogenesis-related process modulation. One of the most promising treatment strategies for AD is immunotherapy. Intensive research is currently underway on both passive immunization, which involves the administration of monoclonal antibodies, and active immunization through vaccinations that stimulate the body to produce specific antibodies. Further research into novel therapeutic directions is essential, particularly concerning the role of the immune system in the pathogenesis of AD. Immunization appears to be a highly promising approach to developing effective methods for preventing AD or delaying the progression of this disease. Full article

Background: Neonatal influenza is a rare condition. Young infants have immature immune defenses and are unable to receive direct vaccination; this can result in significant illness. Maternal anti-influenza immunization during pregnancy provides passive antibodies to the newborn via transplacental transfer, significantly decreasing the incidence and severity of influenza in early infancy. Nevertheless, the vaccination coverage during pregnancy remains low in many regions, leaving certain neonates without adequate protection. Methods: We present three cases of laboratory-confirmed influenza infection in neonates admitted to the “Sf. Ioan” Clinical Emergency Pediatric Hospital in Galați and conduct a literature review. The clinical presentation, co-infections, timing of antiviral therapy, laboratory findings, maternal vaccination status, and outcomes (including the hospitalization duration and recovery) were systematically analyzed for each case. Results: All three neonates were full-term and previously healthy, born to mothers who had not received influenza vaccinations during their pregnancies. They presented at ages ranging from 2 to 4 weeks with fever, respiratory symptoms including a cough, nasal congestion, and respiratory distress, as well as feeding difficulties. One case involved a co-infection with Bordetella pertussis, which manifested as a severe paroxysmal cough, cyanosis, and apnea. Laboratory findings in the cases with influenza alone indicated leukopenia accompanied by normal C-reactive protein levels. In the co-infection case, leukocytosis, lymphocytosis, and thrombocytosis were observed. All the infants received oseltamivir treatment within 48 h of the symptom onset; the case with pertussis co-infection also received azithromycin. Each infant required supplemental oxygen, but none necessitated mechanical ventilation. Clinical improvement was observed in all cases, with hospitalization ranging from 6 to 7 days and complete recovery without complications. Conclusions: Neonatal influenza may result in considerable morbidity, particularly in infants born to unvaccinated mothers. Positive outcomes, however, have been correlated with early diagnosis and antiviral treatment. Pertussis co-infection may exacerbate clinical progression, underscoring the importance of maternal immunization against both influenza and pertussis. In this case series, we aim to present three cases of laboratory-confirmed influenza in neonates born to mothers who were not immunized against influenza during pregnancy. These cases highlight the clinical presentations of neonatal influenza, underscore the risks associated with pertussis co-infection, and reinforce the importance of maternal influenza and Tdap vaccination for preventing severe outcomes in newborns. Full article

The bone marrow microenvironment is a dynamic and complex niche that plays a central role in the development, progression, and therapeutic resistance of leukemia. Among the various stromal and immune cells that compose this microenvironment, adipocytes are increasingly recognized as active participants rather than passive bystanders. These cells contribute to leukemia pathophysiology by supplying leukemic cells with vital metabolic fuels such as free fatty acids and glutamine, which support cellular bioenergetics and biosynthesis. Furthermore, adipocytes secrete adipokines—including leptin, adiponectin, and others—that influence leukemic cell proliferation, apoptosis, and chemoresistance. Leukemic cells, in turn, are not merely recipients of these signals, but actively remodel the marrow niche to their advantage. They can suppress adipogenesis, inhibit the differentiation of mesenchymal stem cells into adipocytes, or reprogram existing adipocytes to adopt a tumor-supportive phenotype. These transformed adipocytes may enhance leukemic cell survival, dampen immune responses, and create a metabolic sanctuary that enables resistance to standard chemotherapies. This reciprocal and dynamic interaction between leukemic cells and adipocytes contributes significantly to minimal residual disease and relapse, posing a major challenge for durable remission. Recent advances in tissue engineering—such as organ-on-chip and 3D co-culture systems—offer promising platforms to recapitulate and study these leukemia–adipocyte interactions with high fidelity. These models facilitate mechanistic insights and provide a foundation for developing novel therapeutic strategies aimed at disrupting the metabolic and paracrine crosstalk within the leukemic niche. Targeting the adipocyte–leukemia axis represents a compelling and underexplored avenue for improving leukemia treatment by sensitizing malignant cells to existing therapies and overcoming the protective influence of the bone marrow microenvironment. Full article

The SARS-CoV-2 virus poses a significant risk to immunocompromised patients, who display weakened immunity and reduced seroconversion following infection and vaccination. In this study, we recruited 19 hospitalized patients with immune disorders (ImCo) and 4 immunocompetent controls (ICC) with COVID-19. We evaluated their serological, humoral, and cellular immune responses at <30 days and >90 days post-symptom onset. ICC patients showed robust B and T cell responses against SARS-CoV-2, indicated by detectable antibody levels, memory antibody-secreting cells (mASCs) towards the spike protein and spike-specific CD4⁺ and CD8⁺ T cells. ImCo patients showed impaired immune responses, with lower levels of B cell responses. Further subdivision of the ImCo patients demonstrates that solid organ transplant (SOT) patients generated B cell responses similar to ICC patients, whereas the other ImCo patients, including patients with hematological malignancies and anti-CD20 therapy, did not. Absolute T cell numbers and spike-specific CD4⁺ and CD8⁺ T cell responses were low in the ImCo patients at <30 days but increased at later time points. Our findings suggest that even when B cell responses were reduced, patients could present a T cell response, suggesting a more successful line of passive immunization for immunocompromised individuals focusing on boosting T cell responses. Full article

Background/Objectives: It remains challenging to treat recurrent ovarian cancer effectively as traditional interventions like chemotherapy and surgery have limited long-term efficacy, highlighting an urgent need for innovative approaches. Immunotherapy offers potential advantages in modulating the immune response against tumor cells and has emerged as a promising strategy in ovarian cancer management. This review discusses various immunotherapy modalities, including active and passive immune strategies, for recurrent ovarian cancer. Methods: We systematically reviewed recent immunotherapy advances for recurrent ovarian cancer, including the efficacy and mechanisms of single and dual immune checkpoint inhibitors, checkpoint inhibitor combinations with chemotherapy or radiotherapy, anti-angiogenic agents, PARP inhibitors, antibody–drug conjugates (ADC), tumor vaccines, and adoptive cell therapies (ACT). Additionally, we assessed emerging research on biomarkers predictive of immunotherapy responsiveness in ovarian cancer. Results: The findings indicate that immunotherapy, particularly combinations involving immune checkpoint inhibitors and other agents, demonstrates promising efficacy in recurrent ovarian cancer, with some therapies showing enhanced benefits in specific subtypes. The immune microenvironment in platinum-sensitive and -resistant cases exhibits distinct immunological profiles, influencing therapy outcomes. Several potential biomarkers have been identified, potentially aiding in patient stratification and treatment optimization. Conclusions: Immunotherapy significantly advances recurrent ovarian cancer treatment, with various combinations potentially improving outcomes. Further research on predictive biomarkers and immune microenvironment characteristics is crucial for personalizing immunotherapy approaches and enhancing their efficacy in managing recurrent ovarian cancer. Full article

Due to their biocompatibility, nontoxicity, and surface conjugation properties, nanomaterials are effective nanocarriers capable of encapsulating chemotherapeutic drugs and facilitating targeted delivery across the blood–brain barrier (BBB). Although research on nanoparticles for brain cancer treatment is still in its early stages, these systems hold great potential to revolutionize drug delivery. Glioblastoma multiforme (GBM) is one of the most common and lethal brain tumors, and its heterogeneous and aggressive nature complicates current treatments, which primarily rely on surgery. One of the significant obstacles to effective treatment is the poor penetration of drugs across the BBB. Moreover, GBM is often referred to as a “cold” tumor, characterized by an immunosuppressive tumor microenvironment (TME) and minimal immune cell infiltration, which limits the effectiveness of immunotherapies. Therefore, developing novel, more effective treatments is critical to improving the survival rate of GBM patients. Current strategies for enhancing treatment outcomes focus on the controlled, targeted delivery of chemotherapeutic agents to GBM cells across the BBB using nanoparticles. These therapies must be designed to engage specialized transport systems, allowing for efficient BBB penetration, improved therapeutic efficacy, and reduced systemic toxicity and drug degradation. Lipid and inorganic nanoparticles can enhance brain delivery while minimizing side effects. These formulations may include epitopes—small antigen fragments that bind directly to free antibodies, B cell receptors, or T cell receptors—that interact with transport systems and enable BBB crossing, thereby boosting therapeutic efficacy. Lipid-based nanoparticles (LNPs), such as liposomes, niosomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), are among the most promising delivery systems due to their unique properties, including their size, surface modification capabilities, and proven biosafety. Additionally, inorganic nanoparticles such as gold nanoparticles, mesoporous silica, superparamagnetic iron oxide nanoparticles, and dendrimers offer promising alternatives. Inorganic nanoparticles (INPs) can be easily engineered, and their surfaces can be modified with various elements or biological ligands to enhance BBB penetration, targeted delivery, and biocompatibility. Strategies such as surface engineering and functionalization have been employed to ensure biocompatibility and reduce cytotoxicity, making these nanoparticles safer for clinical applications. The use of INPs in GBM treatment has shown promise in improving the efficacy of traditional therapies like chemotherapy, radiotherapy, and gene therapy, as well as advancing newer treatment strategies, including immunotherapy, photothermal and photodynamic therapies, and magnetic hyperthermia. This article reviews the latest research on lipid and inorganic nanoparticles in treating GBM, focusing on active and passive targeting approaches. Full article

Cardiovascular disease (CVD) remains a leading global health concern, with atherosclerosis being its principal cause. Standard CVD treatments primarily focus on mitigating cardiovascular (CV) risk factors through lifestyle changes and cholesterol-lowering therapies. As atherosclerosis is marked by chronic arterial inflammation, the innate and adaptive immune systems play vital roles in its progression, either exacerbating or alleviating disease development. This intricate interplay positions the immune system as a compelling therapeutic target. Consequently, immunomodulatory strategies have gained increasing attention, though none have yet reached widespread clinical adoption. Safety concerns, particularly the suppression of host immune defenses, remain a significant barrier to the clinical application of anti-inflammatory therapies. Recent decades have revealed the significant role of adaptive immune responses to plaque-associated autoantigens in atherogenesis, opening new perspectives for targeted immunological interventions. Preclinical models indicate that vaccines targeting specific atherosclerosis-related autoantigens can slow disease progression while preserving systemic immune function. In this context, numerous experimental studies have advanced the understanding of vaccine development by exploring diverse targeting pathways. Key strategies include passive immunization using naturally occurring immunoglobulin G (IgG) antibodies and active immunization targeting low-density lipoprotein cholesterol (LDL-C) and apolipoproteins, such as apolipoprotein B100 (ApoB100) and apolipoprotein CIII (ApoCIII). Other approaches involve vaccine formulations aimed at proteins that regulate lipoprotein metabolism, including proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), and angiopoietin-like protein 3 (ANGPTL3). Furthermore, the literature highlights the potential for developing non-lipid-related vaccines, with key targets including heat shock proteins (HSPs), interleukins (ILs), angiotensin III (Ang III), and a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS-7). However, translating these promising findings into safe and effective clinical therapies presents substantial challenges. This review provides a critical evaluation of current anti-atherosclerotic vaccination strategies, examines their proposed mechanisms of action, and discusses key challenges that need to be overcome to enable clinical translation. Full article

The epidermal growth factor receptor (EGFR) is frequently overexpressed in a variety of human epithelial tumors, and its aberrant activation plays a pivotal role in promoting tumor growth, invasion, and metastasis. The clinically approved passive EGFR-related therapies have numerous limitations. Seven EGFR-ECD epitope peptides (EG1-7) were selected through bioinformatics epitope prediction tools including NetMHCpan-4.1, NetMHCIIpan-3.2, and IEDB Consensus (v2.18 and v2.22) and fused to the translocation domain of diphtheria toxin (DTT). The A549 tumor model was successfully established in a murine mouse model. The vaccine was formulated by combining the adjuvants Alum and CpG and subsequently assessed for its immunogenicity and anti-tumor efficacy. DTT-EG (3;5;6;7) vaccines elicited specific humoral and cellular immune responses and effectively suppressed tumor growth in both prophylactic and therapeutic mouse tumor models. The selected epitopes EG3 (HGAVRFSNNPALCNV145-159), EG5 (KDSLSINATNIKHFK346-360), EG6 (VKEITGFLLIQAWPE398-412), and EG7 (LCYANTINWKKLFGT469-483) were incorporated into vaccines for active immunization, representing a promising strategy for the treatment of tumors with overexpressed epidermal growth factor receptor (EGFR). The vaccine design and fusion method employed in this study demonstrate a viable approach toward the development of cancer vaccines. Full article

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar^−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar^−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar^−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile. Full article

Background/Objectives: Eculizumab is a first-line treatment for atypical hemolytic uremic syndrome (aHUS), and patients undergoing eculizumab therapy may become more susceptible to infection caused by Neisseria meningitidis (Nm). While meningococcal vaccination is required for patients undergoing eculizumab therapy, there is limited knowledge about meningococcal carriage in children with aHUS. We aimed to evaluate (1) the prevalence of Nm carriage, (2) serogroup distribution, and (3) the immunization status of children undergoing eculizumab treatment for aHUS. Methods: The Meningo-aHUS study is a prospective, multi-center study evaluating meningococcal carriage in children and adolescents in Türkiye receiving eculizumab for aHUS. We noted the age, gender, daycare, school, or university attendance, passive smoking status, previous infection and antibiotic use, and previous immunization history, including meningococcal vaccines, from the medical records of those children with aHUS. We collected nasopharyngeal samples, tested them for Nm using real-time polymerase chain reaction, and performed a serogroup analysis on the positive samples. Results: We collected nasopharyngeal samples from 62 children with aHUS. Out of 62 children, 61 (98.4%) had received at least one dose of the meningococcal vaccine. The median time since the last meningococcal vaccine dose was 15 months (1–59 months). We detected meningococcal carriage in three (4.8%, 95% CI 1.0–13.5) children, and all three strains were non-groupable (NG). No other serogroups were detected. Conclusions: Almost all the children received their risk-group meningococcal immunization, including booster doses. A 4.8% of children with aHUS carried NG meningococci and, no vaccine serogroups were detected. Patients treated with eculizumab remain profoundly susceptible to IMD due to these NG meningococcal strains. The occurrence of breakthrough cases and carriage of Nm, especially NG strains, highlights the significance of maintaining a state of constant alertness, promptly seeking medical attention, and swiftly treating any symptoms that align with IMD, regardless of their vaccination status or antibiotic prophylaxis. Full article

Convalescent sera, rich in pathogen-specific antibodies, offers passive immunity to patients with infectious diseases. Screening assays using convalescent sera are crucial for evaluating therapeutic efficacy, selecting suitable serum donors, and standardizing assays. They measure antibody levels, neutralizing potential, and specificity against viruses like SARS-CoV-2, ensuring therapeutic serum contains potent antibodies. Standardized procedures enable reliable results and wider adoption of serum therapy for COVID-19. We have developed a high-content image-based assay for screening convalescent sera against SARS-CoV-2 variants. Using various cell lines, we identified optimal candidates, employed immunofluorescence to visualize infected cells, and assessed neutralizing antibody efficacy. Screening convalescent sera for therapeutic potential identified neutralizing activity against SARS-CoV-2 variants. Dose–response analysis showed variable neutralizing activity, with some sera exhibiting broad neutralization. Additionally, we explored the synergy between neutralizing sera and β-d-N4-hydroxycytidine (NHC), an initial metabolite of molnupiravir. These assays enhance serum therapy’s benefits for COVID-19 treatment and aid in understanding neutralizing activity against SARS-CoV-2 variants, addressing viral challenges. Full article

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs. Full article

Background: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection. Objective: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals. Main findings: Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a “proof of concept” for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative. Full article

Burkholderia cepacia complex infections remain life-threatening to cystic fibrosis patients, and due to the limited eradication efficiency of current treatments, novel antimicrobial therapies are urgently needed. Surface proteins are among the best targets to develop new therapeutic strategies since they are exposed to the host’s immune system. A surface-shaving approach was performed using Burkholderia cenocepacia J2315 to quantitatively compare the relative abundance of surface-exposed proteins (SEPs) expressed by the bacterium when grown under aerobic and microaerophilic conditions. After trypsin incubation of live bacteria and identification of resulting peptides by liquid chromatography coupled with mass spectrometry, a total of 461 proteins with ≥2 unique peptides were identified. Bioinformatics analyses revealed a total of 53 proteins predicted as localized at the outer membrane (OM) or extracellularly (E). Additionally, 37 proteins were predicted as moonlight proteins with OM or E secondary localization. B-cell linear epitope bioinformatics analysis of the proteins predicted to be OM and E-localized revealed 71 SEP moieties with predicted immunogenic epitopes. The protegenicity higher scores of proteins BCAM2761, BCAS0104, BCAL0151, and BCAL0849 point out these proteins as the best antigens for vaccine development. Additionally, 10 of the OM proteins also presented a high probability of playing important roles in adhesion to host cells, making them potential targets for passive immunotherapeutic approaches. The immunoreactivity of three of the OM proteins identified was experimentally demonstrated using serum samples from cystic fibrosis patients, validating our strategy for identifying immunoreactive moieties from surface-exposed proteins of potential interest for future immunotherapies development. Full article

Background: Kidney transplant recipients (KTRs) are likely to develop severe COVID-19 and are less well-protected by vaccines than immunocompetent subjects. Thus, the use of neutralizing anti–SARS-CoV-2 monoclonal antibodies (mAbs) to confer a passive immunity appears attractive in KTRs. Methods: This retrospective monocentric cohort study was conducted between 1 January 2022 and 30 September 2022. All KTRs with a weak antibody response one month after three doses of mRNA vaccine (anti spike IgG < 264 (BAU/mL)) have received tixagevimab-cilgavimab in pre-exposure (group 1), post-exposure (group 2) or no specific treatment (group 3). We compared COVID-19 symptomatic hospitalizations, including intensive care unit hospitalizations, oxygen therapy, and death, between the three groups. Results: A total of 418 KTRs had SARS-CoV-2 infection in 2022. During the study period, we included 112 KTRs in group 1, 40 KTRs in group 2, and 27 KTRs in group 3. The occurrence of intensive care unit hospitalization, oxygen therapy, and COVID-19 death was significantly increased in group 3 compared to group 1 or 2. In group 3, 5 KTRs (18.5%) were admitted to the intensive care unit, 7 KTRs (25.9%) needed oxygen therapy, and 3 KTRs (11.1%) died. Patients who received tixagevimab-cilgavimab pre- or post-exposure had similar outcomes. Conclusions: This retrospective real-life study supports the relative effectiveness of tixagevimab-cilgavimab on COVID-19 infection caused by Omicron, used as a pre- or post-exposure therapy. The continued evolution of Omicron variants has made tixagevimab-cilgavimab ineffective and reinforces the need for new therapeutic monoclonal antibodies for COVID-19 active on new variants. Full article