Exploring parental perspectives: Maternal RSV vaccination versus infant RSV monoclonal antibody.

Respiratory Syncytial Virus poses a significant global public health threat, particularly affecting infants aged less than one year of age. Recently, two forms of passive immunization against infant RSV have been developed and brought to market; nirsevimab a long-acting monoclonal antibody (mAb) and RSV-PreF, a maternal RSV vaccine. The acceptability and uptake of these products will play a pivotal role in determining the success of any national immunization strategy aimed at safeguarding infants from RSV. It is crucial at this time to reflect on the factors that influence parental decisions surrounding immunization to facilitate more informed discussions, enhance healthcare communication, and contribute to the design of effective RSV prevention strategies that resonate with the concerns and aspirations of parents worldwide.

Intravenous immunoglobulins for the treatment of prolonged COVID-19 in immunocompromised patients: a brief report.

Primary humoral deficiency and secondary B-cell depletion may lead to prolonged Sars-Cov-2 infection due to a decreased viral clearance. Prolonged infection is mainly driven by the lack of anti-Sars-Cov-2 immunoglobulin (IVIg) especially in patients with no vaccine response. Anti-spike immunoglobulin can be provided by infusion of convalescent patients' plasma: recent studies highlighted that commercial immunoglobulin show high titers of neutralizing IgG. We conducted a single center retrospective cohort. We included 9 patients (6 males, median age 74 years old): one patient with X-linked agammaglobulinemia and 8 patients treated with rituximab (2 granulomatosis with polyangiitis, 1 neuromyelitis optica, 4 low grade B-cell lymphoma and 1 EBV post-transplant lymphoproliferative disorder). Mean serum globulin was 4 ± 1.6 g/L. 7/8 had received at least 3 doses of mRNA anti-Sars-Cov-2 vaccine (median 4) with no response (anti-Spike IgG 0 for 6 patients). In this specific population requiring oxygen therapy but no intensive care support, the administration of IVIg was well tolerated and provided a swift improvement of clinical status, a significant decrease of inflammation associated to the an improvement of radiological patterns. Our results suggest that immunoglobulin could be used as a salvage therapy as an alternative to convalescent plasma but highly stringent patient selection is required due to the worldwide shortage of IVIg.

Passive immunotherapy for Alzheimer's disease: challenges & future directions.

Passive immunotherapy with specific antibodies targeting Amyloid ß (Aß) peptide or tubulin-associated unit (tau) protein has emerged as a promising therapeutic approach in Alzheimer's disease (AD). However, in a recent phase III clinical study, Sperling et al. (N Engl J Med 10.1056/NEJMoa2305032, 2023) reported that solanezumab, a monoclonal antibody targeting Aß peptide, failed to slow cognitive decline in AD patients. Previously, three other anti-Aß antibodies, bapineuzumab, crenezumab, and gantenerumab, have also failed to show similar beneficial effects. In addition, three humanized antibodies targeting tau protein failed in their phase II trials. However, other anti-Aß antibodies, such as lecanemab (a humanized mAb binds to soluble Aß protofibrils), donanemab (a humanized mAb binds to insoluble, N-terminal truncated form of Aß peptides) and aducanumab (a human mAb binds to the aggregated form of Aß), have been shown to slow the decline of cognitive functions in early stage AD patients. The specific targets used in passive immunotherapy in these clinical trials may explain the divergent clinical outcomes. There are several challenges and limitations of passive immunotherapy using anti-Aß antibodies and long term longitudinal studies are needed to assess their efficacy, side effects and cost effectiveness in a wider spectrum of subjects, from pre-dementia to more advanced dementia. A combination therapeutic approach using both anti-Aß antibodies and other pharmaceutical agents should also be explored.

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19.

Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 ("vax-plasma"). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% (P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization.IMPORTANCEAs SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

Leptospira-specific immunoglobulin Y (IgY) is protective in infected hamsters.

Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects.

Severe Tick-Borne Encephalitis (TBE) in a Patient with X-Linked Agammaglobulinemia; Treatment with TBE Virus IgG Positive Plasma, Clinical Outcome and T Cell Responses.

PURPOSE: A patient with X-linked agammaglobulinemia (XLA) and severe tick-borne encephalitis (TBE) was treated with TBE virus (TBEV) IgG positive plasma. The patient's clinical response, humoral and cellular immune responses were characterized pre- and post-infection. METHODS: ELISA and neutralisation assays were performed on sera and TBEV PCR assay on sera and cerebrospinal fluid. T cell assays were conducted on peripheral blood the patient and five healthy vaccinated controls. RESULTS: The patient was admitted to the hospital with headache and fever. He was not vaccinated against TBE but receiving subcutaneous IgG-replacement therapy (IGRT). TBEV IgG antibodies were low-level positive (due to scIGRT), but the TBEV IgM and TBEV neutralisation tests were negative. During hospitalisation his clinical condition deteriorated (Glasgow coma scale 3/15) and he was treated in the ICU with corticosteroids and external ventricular drainage. He was then treated with plasma containing TBEV IgG without apparent side effects. His symptoms improved within a few days and the TBEV neutralisation test converted to positive. Robust CD8+ T cell responses were observed at three and 18-months post-infection, in the absence of B cells. This was confirmed by tetramers specific for TBEV. CONCLUSION: TBEV IgG-positive plasma given to an XLA patient with TBE without evident adverse reactions may have contributed to a positive clinical outcome. Similar approaches could offer a promising foundation for researching therapeutic options for patients with humoral immunodeficiencies. Importantly, a robust CD8+ T cell response was observed after infection despite the lack of B cells and indicates that these patients can clear acute viral infections and could benefit from future vaccination programs.

Viral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: a systematic review and meta-analysis.

BACKGROUND: Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in outpatients treated for mild-to-moderate COVID-19. METHODS: In this systematic review and meta-analysis, we searched PubMed, Scopus, and medRxiv from database inception to Aug 16, 2023, for randomised placebo-controlled trials that tested virus-directed treatments (ie, any monoclonal antibodies, convalescent plasma, or antivirals) in non-hospitalised individuals with COVID-19. We only included studies that reported both clinical outcomes (ie, rate of disease progression to hospitalisation or death) and virological outcomes (ie, viral load within the first 7 days of treatment). We extracted summary data from eligible reports, with discrepancies resolved through discussion. We used an established meta-regression model with random effects to assess the association between clinical efficacy and virological treatment effect, and calculated I2 to quantify residual study heterogeneity. FINDINGS: We identified 1718 unique studies, of which 22 (with a total of 16 684 participants) met the inclusion criteria, and were in primarily unvaccinated individuals. Risk of bias was assessed as low in 19 of 22 studies for clinical outcomes, whereas for virological outcomes, a high risk of bias was assessed in 11 studies, some risk in ten studies, and a low risk in one study. The unadjusted relative risk of disease progression for each extra log10 copies per mL reduction in viral load in treated compared with placebo groups was 0·12 (95% CI 0·04-0·34; p<0·0001) on day 3, 0·20 (0·08-0·50; p=0·0006) on day 5, and 0·53 (0·30-0·94; p=0·030) on day 7. The residual heterogeneity in our meta-regression was estimated as low (I2=0% [0-53] on day 3, 0% [0-71] on day 5, and 0% [0-43] on day 7). INTERPRETATION: Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a potential surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy. FUNDING: Australian Government Department of Health, Medical Research Future Fund, and Australian National Health and Medical Research Council.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Factors associated with the SARS-CoV-2 immunoglobulin-G titer levels in convalescent whole-blood donors: a Chinese cross-sectional study.

Blood transfusions from convalescent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients could be used to treat patients with severe infections or immunocompromised patients. However, it is necessary to select the optimal donors to maximize the utilization of resources. In this study, we investigated the associations among body mass index (BMI), tobacco smoking, exercise frequency and duration, and alcohol consumption with the SARS-CoV-2 immunoglobulin-G (IgG) antibody titer levels with in the Chinese convalescent blood donor population. Here we show that BMI, smoking habits, and exercise frequency appear to be predictive factors for IgG levels in convalescent male blood donors. However, these variables were not observed as predictive of IgG levels in female convalescent blood donors. The findings could be used to optimize the screening for potential blood donors to treat immunocompromised or severely ill COVID-19 patients.

Dosing of Convalescent Plasma and Hyperimmune Anti-SARS-CoV-2 Immunoglobulins: A Phase I/II Dose-Finding Study.

BACKGROUND AND OBJECTIVE: During the COVID-19 pandemic, trials on convalescent plasma (ConvP) were performed without preceding dose-finding studies. This study aimed to assess potential protective dosing regimens by constructing a population pharmacokinetic (popPK) model describing anti-SARS-CoV-2 antibody titers following the administration of ConvP or hyperimmune globulins (COVIg). METHODS: Immunocompromised patients, testing negative for anti-SARS-CoV-2 spike antibodies despite vaccination, received a range of anti-SARS-CoV-2 antibodies in the form of COVIg or ConvP infusion. The popPK analysis was performed using NONMEM v7.4. Monte Carlo simulations were performed to assess potential COVIg and ConvP dosing regimens for prevention of COVID-19. RESULTS: Forty-four patients were enrolled, and data from 42 were used for constructing the popPK model. A two-compartment elimination model with mixed residual error best described the Nab-titers after administration. Inter-individual variation was associated to CL (44.3%), V1 (27.3%), and V2 (29.2%). Lean body weight and type of treatment (ConvP/COVIg) were associated with V1 and V2, respectively. Median elimination half-life was 20 days (interquartile range: 17-25 days). Simulations demonstrated that even monthly infusions of 600 mL of the ConvP or COVIg used in this trial would not achieve potentially protective serum antibody titers for > 90% of the time. However, as a result of hybrid immunity and/or repeated vaccination, plasma donors with extremely high antibody titers are now readily available, and a > 90% target attainment should be possible. CONCLUSION: The results of this study may inform future intervention studies on the prophylactic and therapeutic use of antiviral antibodies in the form of ConvP or COVIg. CLINICAL TRIAL REGISTRATION NUMBER: NL9379 (The Netherlands Trial Register).

Convalescent Plasma Therapy in Immunocompromised Patients Infected With the BA.1 or BA.2 Omicron SARS-CoV-2.

The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID-19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67-86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic.

Alzheimer's Disease Immunotherapy: Current Strategies and Future Prospects.

Alzheimer's disease (AD) is an extremely complex and heterogeneous pathology influenced by many factors contributing to its onset and progression, including aging, amyloid-beta (Aß) plaques, tau fibril accumulation, inflammation, etc. Despite promising advances in drug development, there is no cure for AD. Although there have been substantial advancements in understanding the pathogenesis of AD, there have been over 200 unsuccessful clinical trials in the past decade. In recent years, immunotherapies have been at the forefront of these efforts. Immunotherapy alludes to the immunological field that strives to identify disease treatments via the enhancement, suppression, or induction of immune responses. Interestingly, immunotherapy in AD is a relatively new approach for non-infectious disease. At present, antibody therapy (passive immunotherapy) that targets anti-Aß aimed to prevent the fibrillization of Aß peptides and disrupt pre-existing fibrils is a predominant AD immunotherapy due to the continuous failure of active immunotherapy for AD. The most rational and safe strategies will be those targeting the toxic molecule without triggering an abnormal immune response, offering therapeutic advantages, thus making clinical trial design more efficient. This review offers a concise overview of immunotherapeutic strategies, including active and passive immunotherapy for AD. Our review encompasses approved methods and those presently under investigation in clinical trials, while elucidating the recent challenges, complications, successes, and potential treatments. Thus, immunotherapies targeting Aß throughout the disease progression using a mutant oligomer-Aß stimulated dendritic cell vaccine may offer a promising therapy in AD.

Charting a path forward: Promising outcomes of convalescent plasma therapy in the care of severely B-cell depleted patients with persistent COVID-19.

BACKGROUND: Patients with severe B-cell depletion related to hematological malignancies or B-cell targeted therapy suffer from impaired antibody responses to SARS-CoV-2 and are at risk for prolonged COVID-19. In this population, COVID-19 convalescent plasma (CCP) may provide passive immunity, enhance immune response, and promote virus neutralization. This study evaluated outcomes of B-cell depleted patients with persistent COVID-19 treated with CCP. STUDY DESIGN AND METHODS: This analysis included all consecutive severely B-cell depleted patients with persistent COVID-19, receiving CCP at Rambam between 01.2022-02.2023. Persistent COVID-19 was defined as the presence of symptoms for ≥14 days in patients with negative SARS-CoV-2 nucleocapsid antibody test results. RESULTS: Twenty patients met inclusion criteria, 17 of whom had hematological malignancies, two suffered from rheumatoid arthritis and one had both. Twelve patients received anti-CD-20 treatment, one - CAR-T cells and three underwent stem cell transplantation. The median duration of COVID-19 symptoms was 27.5 days (range 14-97); 12 patients had mild-to-moderate COVID-19 and 8 had severe infection. Sixteen patients required hospitalization. The majority of patients received other COVID-19 therapies before CCP. Within a median of two days (range 1-16) post-infusion, 19/20 patients clinically improved. No CCP-associated adverse events were documented. COVID-19 symptoms recurred in 3 of the improved patients. Two patients died from COVID-19 on days 1 and 90 following the first CCP infusion. DISCUSSION: In severely B-cell depleted patients with persistent COVID-19, CCP is safe and associated with rapid clinical improvement. This subset of immunocompromised patients could particularly benefit from CCP administration.

Immunization Strategies Against Clostridioides difficile.

Clostridioides difficile (C. difficile) infection (CDI) is an important healthcare but also a community-associated disease. CDI is considered a public health threat and an economic burden. A major problem is the high rate of recurrences. Besides classical antibiotic treatments, new therapeutic strategies are needed to prevent infection, to treat patients, and to prevent recurrences. If fecal transplantation has been recommended to treat recurrences, another key approach is to elicit immunity against C. difficile and its virulence factors. Here, after a summary concerning the virulence factors, the host immune response against C. difficile, and its role in the outcome of disease, we review the different approaches of passive immunotherapies and vaccines developed against CDI. Passive immunization strategies are designed in function of the target antigen, the antibody-based product, and its administration route. Similarly, for active immunization strategies, vaccine antigens can target toxins or surface proteins, and immunization can be performed by parenteral or mucosal routes. For passive immunization and vaccination as well, we first present immunization assays performed in animal models and second in humans and associated clinical trials. The different studies are presented according to the mode of administration either parenteral or mucosal and the target antigens and either toxins or colonization factors.

Polyclonal anti-whole cell IgY passive immunotherapy shields against P. aeruginosa-induced acute pneumonia and burn wound infections in murine models.

Pseudomonas aeruginosa (PA) is a multidrug-resistant (MDR) opportunistic pathogen causing severe hospital-, and community-acquired infections worldwide. Thus, the development of effective immunotherapy-based treatments is essential to combat the MDR-PA infections. In the current study, we evaluated the protective efficacy of polyclonal avian antibodies raised against inactivated whole cells of the PAO1 strain in murine models of acute pneumonia and burn wound. The efficacy of generated antibodies was evaluated against different PA strains through several in vitro, ex vivo and in vivo experiments. The results showed that the anti-PAO1-IgY effectively reduced the motility, biofilm formation and cell internalization ability, and enhanced the opsonophagocytic killing of PA strains through the formation of immobilized bacteria and induction of increased cell surface hydrophobicity. Furthermore, immunotherapy with anti-PAO1-IgY completely protected mice against all PA strains in both acute pneumonia and burn wound murine models. It was found to reduce the bacterial loads in infected burned mice through interfering with virulence factors that play vital roles in the early stages of PA infection, such as colonization and cell internalization. The immunotherapy with anti-PAO1-IgYs could be instrumental in developing effective therapies aimed at reducing the morbidity and mortality associated with PA infections.

The role of graft T-cell size in patients receiving alemtuzumab serotherapy for non-malignant disorders: results of an institutional protocol.

Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243-1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes.

Passive immunotherapy for Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by cognitive impairment with few therapeutic options. Despite many failures in developing AD treatment during the past 20 years, significant advances have been achieved in passive immunotherapy of AD very recently. Here, we review characteristics, clinical trial data, and mechanisms of action for monoclonal antibodies (mAbs) targeting key players in AD pathogenesis, including amyloid-ß (Aß), tau and neuroinflammation modulators. We emphasized the efficacy of lecanemab and donanemab on cognition and amyloid clearance in AD patients in phase III clinical trials and discussed factors that may contribute to the efficacy and side effects of anti-Aß mAbs. In addition, we provided important information on mAbs targeting tau or inflammatory regulators in clinical trials, and indicated that mAbs against the mid-region of tau or pathogenic tau have therapeutic potential for AD. In conclusion, passive immunotherapy targeting key players in AD pathogenesis offers a promising strategy for effective AD treatment.

The Effect of COVID Convalescent Plasma on Hospital Stay: A Retrospective Observational Study from a Tertiary Care Hospital in North India.

INTRODUCTION: COVID convalescent plasma (CCP) has been used as standard of care in patients all over the world. CCP is plasma collected from recently infected and currently recovered COVID-19 patients, which contains antiviral antibodies that can be used to treat patients with COVID-19. Several studies have shown a shorter hospital stay and lower mortality in patients treated with convalescent plasma in comparison with those not treated with it. OBJECTIVES: This study aims to determine the effect of COVID convalescent plasma (CCP) on the length of hospital stay in symptomatic patients and to determine outcome of the disease in patients who were administered CCP. METHODS: This was a retrospective observational study done at a tertiary health care centre from July 2020 to May 2021, including patients who received CCP during the course of their stay in the hospital. RESULTS: Among 257 participants, the patients with multiple comorbidities who were administered CCP had the longest average length of stay in the hospital which was 15 days, out of which, 92 (35.8%) patients were discharged while 9 (3.5%) patients died. Also, the maximum number of deaths was observed in those patients who had no associated comorbidity, being 11 (4.3%). It was observed that earlier administration of CCP in patients (< 5 days from symptom onset) was associated with a higher number of discharges as compared to deaths. CONCLUSION: Our study indicates that CCP may be efficient in treating COVID-19 patients if given in early course of the disease.