Search Results (26)

Background: Pre-exposure passive immune prophylaxis (PrEP) might contribute to improve hematologic malignancy (HM) outcomes; however, there are currently no specific guidelines to inform patient selection. Methods: A literature review and a Delphi consensus process were used to identify COVID-19 risk factors, critical COVID-19 outcomes, and efficacy of PrEP against SARS-CoV-2 in HMs. An analytic hierarchy process was used to assign a priority score to candidate outcomes and to determine the PrEP indications. For these decisions, the experts assumed adequate compliance with anti-COVID-19 vaccination and acknowledged the effectiveness of PrEP in reducing SARS-CoV-2-related mortality and hospital admissions. Results: Based on the literature review, the expert panel identified 80 risk categories among patients with HM and prioritized eight clinical outcomes related to SARS-CoV-2 PrEP. The highest mean priority scores were observed for HM-related mortality (7.0), intensive care unit admission (6.7), and delays in anti-HM treatment (6.6). Based on such a framework, the experts deemed that if there was a variant-specific PrEP promptly available, it would be considered mandatory for all candidates receiving allogeneic hematopoietic cell transplantation, CAR-T therapy, or bispecific antibodies, regardless of local viral epidemiology. During epidemiological waves, variant-specific PrEP would also be recommended for patients with HMs at high risk of unfavorable COVID-19 clinical outcomes. Conclusions: This study identified PrEP indications for patients with HM receiving appropriate active immunization against COVID-19. Full article

Background/Objectives: Respiratory syncytial virus (RSV) bronchiolitis remains a leading cause of hospitalization in infants. In the 2024–2025 season, passive newborn immunization with nirsevimab, a long-acting anti-RSV monoclonal antibody, was introduced for the first time in Italy. However, the immunization campaign was not uniformly implemented on a regional basis due to supply and organizational difficulties. The aim of the study was to assess the real-world impact of nirsevimab prophylaxis during the 2024–2025 bronchiolitis season in four regions of Italy. Methods: This multicenter observational study included infants <12 months hospitalized for bronchiolitis across four Italian centers. Hospitalizations due to RSV and non-RSV bronchiolitis were compared across the 2023–2024 and 2024–2025 seasons, in relation to the timing and coverage of nirsevimab’s introduction in each of the four regions. Results: Early and widespread nirsevimab administration was associated with a significant reduction in RSV hospitalizations and severity of disease. Centers located in regions that had delayed implementation of immunization observed higher RSV burden and intensive care unit admissions. Admissions for non-RSV bronchiolitis remained stable. Conclusions: Timely and universal administration of nirsevimab significantly reduced RSV hospitalizations and severity, while delayed implementation resulted in limited benefit. These findings support early and uniform prophylaxis to mitigate health disparities and seasonal pressure on pediatric healthcare systems. 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

Ricin is a highly potent toxin that has been used in various attempts at bioterrorism worldwide. Although a vaccine for preventing ricin poisoning (RiVax™) is in clinical development, there are currently no commercially available prophylaxis or treatments for ricin intoxication. Numerous studies have highlighted the potential of passive immunotherapy using anti-ricin monoclonal antibodies (mAbs) and have shown promising results in preclinical models. In this article, we describe the neutralizing and protective efficacy of a new generation of high-affinity anti-ricin mAbs, which bind and neutralize very efficiently both ricin isoforms D and E in vitro through cytotoxicity cell assays. In vivo, protection assay revealed that one of these mAbs (RicE5) conferred over 90% survival in a murine model challenged intranasally with a 5 LD₅₀ of ricin and treated by intravenous administration of the mAbs 6 h post-intoxication. Notably, a 35% survival rate was observed even when treatment was administered 24 h post-exposure. Moreover, all surviving mice exhibited long-term immunity to high ricin doses. These findings offer promising results for the clinical development of a therapeutic candidate against ricin intoxication and may also pave the way for novel vaccination strategies against ricin or other toxins. Full article

Passive immunisation with normal human immunoglobulin (NHIG) is recommended as post-exposure prophylaxis (PEP) for higher-risk measles contacts where vaccination is contraindicated. However, the concentration of measles-specific antibodies in NHIG depends on antibody levels within pooled donor plasma. There are concerns that measles immunity in the Australian population may be declining over time and that blood donors’ levels will progressively decrease, impacting levels required to produce effective NHIG for measles PEP. A cross-sectional study of Australian plasmapheresis donors was performed using an age-stratified, random sample of recovered serum specimens, collected between October and November 2019 (n = 1199). Measles-specific IgG antibodies were quantified by ELISA (Enzygnost anti-measles virus IgG, Siemens), and negative and equivocal specimens (n = 149) also underwent plaque reduction neutralisation testing (PRNT). Mean antibody levels (optical density values) progressively decreased from older to younger birth cohorts, from 2.09 [±0.09, 95% CI] to 0.58 [±0.04, 95% CI] in donors born in 1940–1959 and 1990–2001, respectively (p < 0.0001). This study shows that mean measles-specific IgG levels are significantly lower in younger Australian donors. While current NHIG selection policies target older donors, as younger birth cohorts become an increasingly larger proportion of contributing donors, measles-specific antibody concentrations of NHIG will progressively reduce. We therefore recommend monitoring measles-specific antibody levels in future donors and NHIG products in Australia and other countries that eliminated measles before the birth of their youngest blood donors. Full article

Objective. We aimed to report the real-world use and outcomes over time in immunocompromised individuals receiving tixagevimab/cilgavimab (T/C) pre-exposure prophylaxis (PrEP). Methods. This observational study included participants who received T/C PrEP, categorized into three groups: (i) No COVID-19 (NoC), i.e., participants who never had COVID-19; (ii) Hybrids (H), i.e., participants who had COVID-19 before PrEP; and (iii) Break-through Infections (BTIs), i.e., participants who had COVID-19 after PrEP. The study measured several immune markers at the administration of T/C (T0) at 3 (T1), 6 (T2), and 9 (T3) months afterward. These markers included: anti-receptor-binding domain (RBD) IgG antibodies; BA.5-neutralizing antibodies (nAbs); mucosal IgG; and T cell immunity. The incidence rate ratios for BTIs were analyzed using a Poisson regression model. Results. A total of 231 participants with a median age of 63 years (IQR 54.0–73.0). were included. Among these, 84% had hematological diseases and received a median of three vaccine doses. N = 72 participants belonged to the NoC group, N = 103 to the H group, and n = 56 to the BTI group (24%), with most BTIs being mild/moderate. The incidence rate (IR) of BTIs was 4.2 per 100 patient-months (95% CI 3.2–5.4), with no associated risk factors identified. There was a significant increase in anti-RBD IgG levels 3 months after the T/C administration in all groups, followed by a decline at 6 months, whereas at the same time points, geometric mean titers (GMTs) of anti-BA.5 nAbs were low for all groups and were around or below the detection threshold. No significant changes were observed in IFN-γ levels. The mucosal immune response was observed only 3 months after the PrEP administration. Conclusion. We provided a real-world experience model on the clinical efficacy of T/C PrEP in preventing severe COVID-19 during the Omicron wave through a comprehensive virological and immunological study. While waiting for the arrival of new monoclonal antibodies that can effectively neutralize the most recent variants, T/C PrEP remains the only viable strategy in the available armamentarium today to prevent COVID-19 complications in an extremely fragile population with suboptimal immune responses to COVID-19 vaccines. Full article

Rabies encephalitis is a fatal zoonotic viral disease caused by the neurotropic rabies virus. It remains a major public health concern as it causes almost 100% fatality and has no effective medication after the onset of the disease. However, this illness is preventable with the timely administration of effective post-exposure prophylaxis (PEP) consisting of the rabies vaccine and passive immune globulins (HRIG and ERIG). Recently, conventional PEP has been shown to have many limitations, resulting in little support for these expensive and heterologous globulins. Monoclonal antibody (mAb) production via recombinant technology in animal and human cell cultures, as well as a plant-based platform, was introduced to overcome the costly and high-tech constraints of former preparations. We used transient expression technology to produce two mAbs against the rabies virus in Nicotiana benthamiana and compared their viral neutralizing activity in vitro and in vivo. The expression levels of selective mAbs E559 and 62-71-3 in plants were estimated to be 17.3 mg/kg and 28.6 mg/kg in fresh weight, respectively. The plant-produced mAbs effectively neutralized the challenge virus CVS-11 strain in a cell-based RFFIT. In addition, the combination of these two mAbs in a cocktail protected hamsters from rabies virus infection more effectively than standard HRIG and ERIG. This study suggests that the plant-produced rabies antibody cocktail has promising potential as an alternative biological to polyclonal RIG in rabies PEP. Full article

Novel lyssaviruses, the causative agents of rabies, continue to be described mostly due to increased surveillance in bat hosts. Biologicals for the prevention of rabies in humans have, however, remained largely unchanged for decades. This study aimed to determine if commercial rabies immunoglobulin (RIG) could neutralize diverse lyssaviruses. Two commercial preparations, of human or equine origin, were evaluated against a panel consisting of 13 lyssavirus species. Reduced neutralization was observed for the majority of lyssaviruses compared to rabies virus and was more evident for lyssaviruses outside of phylogroup I. Neutralization of more diverse lyssaviruses only occurred at very high doses, except for Ikoma lyssavirus, which could not be neutralized by the RIG evaluated in this study. The use of RIG is a crucial component of rabies post-exposure prophylaxis and the data generated here indicate that RIG, in its current form, will not protect against all lyssaviruses. In addition, higher doses of RIG may be required for neutralization as the genetic distance from vaccine strains increases. Given the limitations of current RIG preparations, alternative passive immunization options should be investigated. Full article

Since December 2019, many drugs have been evaluated or advocated as potential treatments of SARS-CoV-2 induced disease (COVID-19), including many repositioned drugs and some others specifically developed for these diseases. They can be roughly classified into three categories according to their main mechanism of action (passive immunization, direct antivirals, and anti-inflammatory treatments), and their use depends on the stage of the disease. Despite often promising preclinical data, most of the treatments evaluated failed to show a significant clinical benefit. In addition, a few others have seen their effectiveness affected by the occurrence of SARS-CoV-2 variants and sub-variants. Herein, the aim of this article is to take stock of the data available as of the 14th of July 2022, concerning the specific healing options evaluated for patients suffering from COVID-19. We focus particularly on healing treatments of COVID-19 and do not deal with preventive treatments such as vaccine. Associated therapies such as venous thromboembolism prophylaxis are not detailed since they are covered in a specific chapter of this issue. Passive immunization, especially through monoclonal antibodies, showed a positive impact on the clinical evolution, whether in outpatients or inpatients without oxygen supply. However, their effectiveness strongly depends on the type of SARS-CoV-2 variant, and often decreases or even vanishes with the most recent variants. Among direct antiviral treatments, ritonavir-boosted nirmatrelvir appears to currently be the cornerstone in the management of early infections, but its use may be limited by drug interactions. Remdesivir remains as an alternative in this situation, even though it is potentially less convenient. Anti-inflammatory treatments have often been shown to be the most effective in inpatients with oxygen supply. Dexamethasone is now a cornerstone of management of these patients. Added tocilizumab seems beneficial in the case of hyper inflammation. JAK inhibitors and anakinra have also gained an interest in some studies. As a conclusion of this narrative review, the best treatment strategy has yet to be defined and is likely to evolve in the future, not only because many other drugs are still under development and evaluation, but also because of the viral epidemics and epidemiology evolution. Full article

This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, Clostridium tetani, Clostridium botulinum. The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines. Full article

Background: Tixagevimab/cilgavimab (TGM/CGM) are neutralizing monoclonal antibodies (mAbs) directed against different epitopes of the receptor-binding domain of the SARS-CoV-2 spike protein that have been considered as pre-exposure prophylaxis (PrEP). Objectives: This study seeks to assess the efficacy and safety of TGM/CGM to prevent COVID-19 in patients at high risk for breakthrough and severe SARS-CoV-2 infection who never benefited maximally from SARS-CoV-2 vaccination and for those who have a contraindication to SARS-CoV-2 vaccines. Design: This study is a systematic review and meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed. Methods: Electronic databases (PubMed, CINAHL, Embase, medRxiv, ProQuest, Wiley online library, Medline, and Nature) were searched from 1 December 2021 to 30 November 2022 in the English language using the following keywords alone or in combination: 2019-nCoV, 2019 novel coronavirus, COVID-19, coronavirus disease 2019, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, tixagevimab, cilgavimab, combination, monoclonal, passive, immunization, antibody, efficacy, clinical trial, cohort, pre-exposure, prophylaxis, and prevention. We included studies in moderate to severe immunocompromised adults (aged ≥18 years) and children (aged ≥12 years) who cannot be vaccinated against COVID-19 or may have an inadequate response to SARS-CoV-2 vaccination. The effect sizes of the outcome of measures were pooled with 95% confidence intervals (CIs) and risk ratios (RRs). Results: Of the 76 papers that were identified, 30 articles were included in the qualitative analysis and 13 articles were included in the quantitative analysis (23 cohorts, 5 case series, 1 care report, and 1 randomized clinical trial). Studies involving 27,932 patients with high risk for breakthrough and severe COVID-19 that reported use of TGM/CGM combination were analyzed (all were adults (100%), 62.8% were men, and patients were mainly immunocompromised (66.6%)). The patients’ ages ranged from 19.7 years to 79.8 years across studies. TGM/CGM use was associated with lower COVID-19-related hospitalization rate (0.54% vs. 1.2%, p = 0.27), lower ICU admission rate (0.6% vs. 5.2%, p = 0.68), lower mortality rate (0.2% vs. 1.2%, p = 0.67), higher neutralization of COVID-19 Omicron variant rate (12.9% vs. 6%, p = 0.60), lower proportion of patients who needed oxygen therapy (8% vs. 41.2%, p = 0.27), lower RT-PCR SARS-CoV-2 positivity rate (2.1% vs. 5.8%, p < 0.01), lower proportion of patients who had severe COVID-19 (0% vs. 0.5%, p = 0.79), lower proportion of patients who had symptomatic COVID-19 (1.8% vs. 6%, p = 0.22), and higher adverse effects rate (11.1% vs. 10.7%, p = 0.0066) than no treatment or other alternative treatment in the prevention of COVID-19. Conclusion: For PrEP, TGM/CGM-based treatment can be associated with a better clinical outcome than no treatment or other alternative treatment. However, more randomized control trials are warranted to confirm our findings and investigate the efficacy and safety of TGM/CGM to prevent COVID-19 in patients at risk for breakthrough or severe SARS-CoV-2 infection. Full article

Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. Results: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum–antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. Conclusions: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed. Full article

The coronavirus disease 2019 (COVID-19) pandemic has posed significant global challenges for solid organ transplant (SOT) recipients. Mortality rates of COVID-19 in this patient population remain high, despite new available therapeutic options and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination. Priority access to SARS-CoV-2 vaccination for waitlisted candidates and for SOT patients and their family members is recommended since the advantage from vaccination reduces the risk of COVID-19-related complications. However, immunogenicity and efficacy of COVID-19 vaccines are lower in waitlisted candidates and SOT recipients than in the general population. Routine systematic assessment of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, although highly recommended for investigation and improvement of knowledge. SOT recipients should continue to adhere to preventive protective measures despite vaccination and may undergo passive antibody prophylaxis. This article seeks to provide an update on SARS-CoV-2 vaccination and preventive measures in SOT recipients based on existing literature and international guidelines. Full article

Almost four decades on, since the 1980’s, with hundreds of HIV vaccine candidates tested in both non-human primates and humans, and several HIV vaccines trials later, an efficacious HIV vaccine continues to evade us. The enormous worldwide genetic diversity of HIV, combined with HIV’s inherent recombination and high mutation rates, has hampered the development of an effective vaccine. Despite the advent of antiretrovirals as pre-exposure prophylaxis and preventative treatment, which have shown to be effective, HIV infections continue to proliferate, highlighting the great need for a vaccine. Here, we provide a brief history for the HIV vaccine field, with the most recent disappointments and advancements. We also provide an update on current passive immunity trials, testing proof of the concept of the most clinically advanced broadly neutralizing monoclonal antibodies for HIV prevention. Finally, we include mucosal immunity, the importance of vaccine-elicited immune responses and the challenges thereof in the most vulnerable environment–the female genital tract and the rectal surfaces of the gastrointestinal tract for heterosexual and men who have sex with men transmissions, respectively. Full article

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab’s usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio. Full article