scholarly journals Efficacy of COVID-19 Pathogen Inactivated Convalescent Plasma for Patients with Moderate to Severe Acute COVID-19: A Case Matched Control Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Nina Khanna ◽  
Maja Weisser ◽  
Anemone Hedstueck ◽  
Sarah Tschudin Sutter ◽  
Sandra Roesch ◽  
...  
Keyword(s):  
Cardiogenic Shock ◽  
San Francisco ◽  
Viral Clearance ◽  
Antibody Responses ◽  
Publicly Traded ◽  
Private Company ◽  
Transmitted Infection ◽  
Exact Test ◽  
Transfusion Transmitted Infection ◽  
Antibody Titers

Background. COVID-19, caused by the SARS-CoV-2 virus, is a pandemic disease with high morbidity and mortality. Currently, available therapeutic options for COVID-19 are limited. Prior experience in epidemics with convalescent plasma (CP) containing antibodies to viruses has demonstrated variable indications of therapeutic efficacy for: Influenza, Argentine Hemorrhagic Fever, and SARS. Characterizing antibody titers to viruses has indicated correlation with therapeutic efficacy. Convalescent COVID-19 patients with potent SARS-CoV-2 antibody responses can serve as plasma donors for immune therapy. However, antibody responses are variable, many donors are first-time higher risk blood donors, and rapid assays to select optimal CP immune efficacy are limited. Pathogen inactivation (PI) of CP can reduce the risk of transfusion-transmitted infection by unrecognized pathogens. Objectives. This study characterized COVID-19 PI-CP activity; and evaluated efficacy and safety of PI CP transfusion in a case matched controlled cohort of acute COVID-19 patients. Methods. COVID-19 apheresis CP (650 - 1300 mL) was collected from nasopharyngeal PCR + outpatients following 2 PCR negative tests or 28 days after symptom resolution. Amotosalen-UVA PI of CP (INTERCEPT Blood System for Plasma) was performed, and antibody efficacy before and after PI was characterized by: VSV reporter pseudo-virus plaque neutralization (RVPN) NT-50 titer (Vitalant Research Institute, San Francisco), antibody to S and N virus proteins by agglutination-dependent antibody PCR (ADAP, Enable Biosciences, San Francisco), virus ACE-2 soluble receptor neutralization assay (Enable Biosciences), and SARS-CoV-2 antibody profile by coronavirus microarray (University of California, Irvine). Patient inclusion criteria were: confirmed SARS-CoV-2 infection, hospitalization, pulmonary infiltrates, availability of ABO compatible CP, and informed consent. CP patients were matched with control patients (CTRL) for disease severity at diagnosis by standardized clinical risk score (W. Liang et al JAMA Intern Med 2020) and concomitant Tocilizumab use. CP Patients received a total of 400 mL of PI CP from 2 donors over 48 hours and standard therapy. CTRL patients received standard COVID-19 therapy without CP. The primary outcome was in-hospital death to day 28. Secondary outcomes included: progression to intubation, admission to ICU, time to discharge, serious adverse events, NP viral clearance, plasma viral clearance, and humoral immune responses. Differences between CP and CTRL patients were assessed by the Mann-Whitney test for continuous variables, and by Fisher's exact test for categorical variables. Progression to ICU and intubation were analyzed as odds ratios calculated by conditional logistic regression. Results. 15 CP and 30 CTRL patients were enrolled. One CP patient was admitted in cardiogenic shock. Only 2 of 15 CP cohort patients had detectable IgG antibody to SARS CoV-2 S1 antigen at study entry. 3 of 15 PI CP donors had negligible SARS CoV-2 IgG antibodies to all antigens, and demonstrated poor neutralization efficacy. 12/15 CP had effective RVPN titers (> 1:80), RVPN titers were correlated with ACE-2 neutralization antibody titers (r2 = 0.83), and had significant activity specific for S and RBD antigens by microarray profiling (Figure 1). SARS CoV-2 antibody levels were variable between CP donors, but not impacted by PI (Figure 1). Baseline characteristics of CP and matched CTRL patients were similar (Table 1). Sensitivity analysis was performed assessing mortality after exclusion of one CTRL patient admitted in cardiogenic shock and the 2 respective controls. In-hospital 28-day mortality was lower in the CP cohort (0/14) compared to 5/28 CTRL, p = 0.151, 2-sided Fisher's exact test. Progression to intubation, ICU admission, and days in hospital were not significantly different (Table 1). There was a trend toward decreased inflammatory response (CRP normalization) in CP patients. Conclusions. In hospital mortality of COVID-19 patients was lower in the PI-CP cohort, but not statistically significant. 15% of CP had ineffective antibody by multiple assays. However, PI did not impact CP anti-SARS-CoV-2 activity. PI of plasma provides reduced risk of transfusion transmitted infection from COVID-19 CP donors. In this study, PI CP was safe, and may be effective for early treatment of hospitalized COVID-19 patients. Disclosures von Goetz: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Khan:Nanommune Inc.: Current equity holder in private company. Tsai:Enable Biosciences: Current Employment. Robinson:Enable Biosciences: Current Employment. Seftel:Enable Biosciences: Current Employment, Current equity holder in private company. Bagri:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Corash:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company.

Evaluation of Two Tetravalent (ACYW135) Meningococcal Vaccines in Infants and Small Children: A Clinical Study Comparing Immunogenicity of O-Acetyl-Negative and O-Acetyl-Positive Group C Polysaccharides

PEDIATRICS ◽  
1985 ◽  
Vol 76 (1) ◽  
pp. 91-96
Author(s):  
Heikki Peltola ◽  
Assad Safary ◽  
Helena Käyhty ◽  
Viena Karanko ◽  
Francis E. André
Keyword(s):  
Clinical Study ◽  
Elevated Temperatures ◽  
Age Groups ◽  
Antibody Responses ◽  
Meningococcal Vaccine ◽  
Small Children ◽  
Positive Group ◽  
Systemic Reactions ◽  
Antibody Titers ◽  
Group A

Two different tetravalent polysaccharide vaccines against group A, C, Y, and W135 meningococci were given to 118 infants aged 6 to 23 months; the same vaccines were administered in a second dose 12 months later to those infants aged 6 to 11 months at first vaccination. Forty of the infants received vaccine containing the nonacetylated group C polysaccharide C(OAc-) and 78 the acetylated group C polysaccharide C(OAc+) together with group A, Y, and W135 polysaccharides. All polysaccharides, at a dose of 30 µg, induced antibody responses after administration of both vaccines in all age groups although the responses were better in the older infants. Acetylation of the sialic acid of the group C polysaccharide did not significantly influence the response. Rapid decreases in the antibody titers after the first vaccination stressed the need for one or more revaccinations. Vaccination elicited mild local and systemic reactions. Elevated temperatures were more common in the youngest infants but only four developed fever exceeding 38.5°C (101.3°F). We conclude that tetravalent (ACYW135) meningococcal vaccine is safe and immunologically effective in children younger than age 2 years. However, revaccinations may be required to maintain immunity.

ALX148, a CD47 Blocker, in Combination with Rituximab in Patients with Non-Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14 ◽  
Author(s):  
Tae Min Kim ◽  
Nehal Lakhani ◽  
Justin Gainor ◽  
Manali Kamdar ◽  
Philip Fanning ◽  
...  
Keyword(s):  
Immune Response ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Tolerability Profile ◽  
Low Grade ◽  
Publicly Traded ◽  
Private Company ◽  
Non Hodgkin Lymphoma ◽  
Time Of Presentation

Background: CD47 is a myeloid checkpoint upregulated by tumor cells to evade the host's immune response. The high affinity CD47 blocker fusion protein, ALX148, is linked to an inactive immunoglobulin Fc region to minimize toxicity. ALX148 is half the size of an antibody, has been well tolerated, and enhances the innate and adaptive immune response against cancer in combination with anticancer therapeutics across solid and hematologic tumors (ASCO 2020 #3056, EHA 2020 #EP1247). Characterization of ALX148's tolerability profile and antitumor activity in combination with rituximab are reported in patients (pts) with non-Hodgkin Lymphoma (NHL). Methods: Patients with relapsed or refractory CD20-positive B-cell NHL for which no curative therapy was available received ALX148 (10 mg/kg QW or 15 mg/kg QW) in combination with rituximab (375 mg/m2 weekly for 4 doses followed by once monthly for 8 doses). The primary endpoint for the safety population was dose limiting toxicity (DLT). Tumor response, pharmacokinetic (PK), and pharmacodynamic (PD) markers were assessed in all pts. Data are reported as of 30Jun2020 in these fully enrolled cohorts with final data to be updated at the time of presentation. Results: A total of 33 patients with NHL were administered ALX148 in combination with rituximab. Twenty-two pts with median age of 66 years (range 32-80) were administered ALX148, 10 mg/kg QW (ALX10), in combination with rituximab [DLBCL, n=11; mantle cell lymphoma (MCL), n=4; follicular lymphoma (FL), n=5; and marginal zone lymphoma (MZL), n=2]. Eleven pts with median age of 64 years (range 53-78) were administered ALX148, 15 mg/kg QW (ALX15), in combination with rituximab (DLBCL, n=6; MCL, n=1; FL, n=3; and MZL, n=1). There have been no DLTs reported in the fully enrolled safety cohorts, and the MTD of ALX148 in combination with rituximab has not been reached. The maximum ALX148 administered dose is 15 mg/kg QW. Twenty-eight pts experienced any AE, while 16 pts reported mostly low grade treatment-related adverse events (TRAE). The most common TRAEs were rash (21%, n=7), fatigue (9%, n=3), anemia, nausea, neutropenia, and pruritus (6%, n=2 each). With a median follow up of 14 months, objective responses were observed across all histologies in response-evaluable ALX10 pts: 40.9% ORR (4CR,5PR, 6SD, n=22 total) and with a median follow up of 9 months in ALX15 pts: 63.6% ORR (3CR, 4PR, 1SD, n=11 total). Preliminary results indicate favorable ALX148 PK and near complete CD47 receptor occupancy across the dosing interval. Final results will be updated at time of presentation. Conclusions: ALX148 demonstrates excellent tolerability with durable responses in combination with rituximab in patients with relapsed/refractory NHL. The MTD of ALX148 in combination with rituximab was not reached. Encouraging preliminary activity and favorable PK/PD characteristics in combination with rituximab were observed at all dose levels with greater objective response rates reported at the MAD of 15 mg/kg QW. Disclosures Kim: Boryung: Consultancy; Voronoi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Takeda: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; AstraZeneca: Consultancy. Lakhani:incyte: Research Funding; merck: Research Funding; mersana: Research Funding; northern biologics: Research Funding; odonate: Research Funding; pfizer: Research Funding; ikena: Research Funding; symphogen: Research Funding; taiRx: Research Funding; tesaro: Research Funding; livzon: Research Funding; loxo: Research Funding; macrogenics: Research Funding; inhibRx: Research Funding; cytomx: Research Funding; formation biologics: Research Funding; forty seven inc: Research Funding; alexion Pharmaceuticals: Research Funding; Alpine Biosciences: Research Funding; ALX Oncology Inc.: Research Funding; Apexian: Research Funding; asana biosciences: Research Funding; ascentage pharma: Research Funding; beigene: Research Funding; celgene: Research Funding; cerulean pharma: Research Funding; constellation pharma: Research Funding; coordination therapeutics: Research Funding; regeneron: Research Funding; sapience therapeutics: Research Funding; shattuck labs: Research Funding; innovent bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; jounce therapeutics: Research Funding. Gainor:theravance: Consultancy; adaptimmune: Research Funding; ariad: Research Funding; astrazeneka: Research Funding; blueprint medicines: Research Funding; lily: Consultancy; gilead sciences: Consultancy; merck: Consultancy, Research Funding; moderna therapeutics: Consultancy, Research Funding; tesaro: Research Funding; blueprint medicines: Consultancy; novartis: Research Funding; oncorus: Consultancy; regeneron: Consultancy; bristol-myers Squibb: Consultancy, Research Funding; amgen: Consultancy; array biopharma: Consultancy, Research Funding; agios: Consultancy; ironwood pharmaceuticals: Consultancy; takeda: Consultancy; genentech: Consultancy, Research Funding; jounce therapeutics: Consultancy, Research Funding. Kamdar:Roche: Research Funding. Fanning:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Squifflet:ALX Oncology Inc.: Consultancy; IDDI: Current Employment. Jin:ALX Oncology Inc.: Current Employment. Forgie:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company; Pfizer Inc.: Ended employment in the past 24 months. Wan:Tallac Therapeutics: Current Employment, Current equity holder in private company; ALX Oncology Inc.: Consultancy, Current equity holder in publicly-traded company. Pons:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Randolph:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Kim:F. Hoffmann-La Roche: Research Funding; Pfizer: Research Funding; JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding.

scholarly journals Characterization of the Antibacterial Activity of an SiO2 Nanoparticular Coating to Prevent Bacterial Contamination in Blood Products

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 107
Author(s):  
Sahra Fonseca ◽  
Marie-Pierre Cayer ◽  
K. M. Tanvir Ahmmed ◽  
Nima Khadem-Mohtaram ◽  
Steve J. Charette ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Contamination ◽  
Polymeric Materials ◽  
L929 Cell ◽  
Bacterial Strains ◽  
Transmitted Infection ◽  
Log Reduction ◽  
Plasticized Pvc ◽  
Transfusion Transmitted Infection ◽  
Field Electron Microscopy

Technological innovations and quality control processes within blood supply organizations have significantly improved blood safety for both donors and recipients. Nevertheless, the risk of transfusion-transmitted infection remains non-negligible. Applying a nanoparticular, antibacterial coating at the surface of medical devices is a promising strategy to prevent the spread of infections. In this study, we characterized the antibacterial activity of an SiO2 nanoparticular coating (i.e., the “Medical Antibacterial and Antiadhesive Coating” [MAAC]) applied on relevant polymeric materials (PM) used in the biomedical field. Electron microscopy revealed a smoother surface for the MAAC-treated PM compared to the reference, suggesting antiadhesive properties. The antibacterial activity was tested against selected Gram-positive and Gram-negative bacteria in accordance with ISO 22196. Bacterial growth was significantly reduced for the MAAC-treated PVC, plasticized PVC, polyurethane and silicone (90–99.999%) in which antibacterial activity of ≥1 log reduction was reached for all bacterial strains tested. Cytotoxicity was evaluated following ISO 10993-5 guidelines and L929 cell viability was calculated at ≥90% in the presence of MAAC. This study demonstrates that the MAAC could prevent bacterial contamination as demonstrated by the ISO 22196 tests, while further work needs to be done to improve the coating processability and effectiveness of more complex matrices.

scholarly journals Simultaneous Immunization with Multiple Diverse Immunogens Alters Development of Antigen-Specific Antibody-Mediated Immunity

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 964
Author(s):  
Kelsey A. Pilewski ◽  
Kevin J. Kramer ◽  
Ivelin S. Georgiev
Keyword(s):  
Specific Antibody ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Emerging Pathogens ◽  
Igg Antibody ◽  
Neisseria Meningitides ◽  
Immunization Strategies ◽  
Single Antigen ◽  
The Face ◽  
Antibody Titers

Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have recently proven insufficient in the face of many highly mutable and emerging pathogens, modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a focused, protective immune response. However, the effect of cocktail vaccination (simultaneous immunization with multiple immunogens) on the antibody response to each individual antigen within the combination, remains largely unstudied. To investigate whether immunization with a cocktail of diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail compared to immunization with each antigen alone, we immunized mice with surface proteins from uropathogenic Escherichia coli, Mycobacterium tuberculosis, and Neisseria meningitides, and monitored the development of antigen-specific IgG antibody responses. We found that antigen-specific endpoint antibody titers were comparable across immunization groups by study conclusion (day 70). Further, we discovered that although cocktail-immunized mice initially elicited more robust antibody responses, the rate of titer development decreases significantly over time compared to single antigen-immunized mice. Investigating the basic properties that govern the development of antigen-specific antibody responses will help inform the design of future combination immunization regimens.

scholarly journals Splenectomy and its relation to non-transfusion-transmitted infection in thalassemic patients

2016 ◽  
Vol 46 (3) ◽  
pp. 134
Author(s):  
Mururul Aisyi ◽  
Alan Roland Tumbelaka ◽  
Bulan Ginting Munthe ◽  
Bambang Madiyono
Keyword(s):  
Risk Factors ◽  
Common Cold ◽  
Severe Infection ◽  
Cross Sectional Study ◽  
Control Group ◽  
Transmitted Infection ◽  
Cross Sectional ◽  
Transfusion Transmitted Infection ◽  
Common Group ◽  
Level Of Significance

Background Splenectomy has been associated with an increasedsusceptibility to infection. Overwhelming postspelenectomy infec-tion (OPSI) can lead to high mortality. Decreased IgM and tuftsinconcentration on splenectomized patients seems to play a role ininfection’s susceptibility. Many studies have been performed todetermine the risk factors of infection in thalassemic patients.Objective To find out morbidity patterns and risk factors for pre-dicting the likelihood of infection in splenectomized thalassemicpatients.Methods A retrospective cross sectional study was conducted onconfirmed thalassemic children who came to Department of ChildHealth, Cipto Mangunkusumo Hospital within the period of 1973-2003. Splenectomized patients were categorized as cases groupand non-splenectomized patients as control group. Risk factors fordevelopment of common cold and diarrhea were analyzed usingchi-square test with level of significance <0.05.Results A total of 300 thalassemic patients, 100 of them were sple-nectomized, were enrolled in this study. The 15-year-age group orabove is the most common group underwent splenectomy (35%).Common cold is the most common mild infection in both splenec-tomized group (75%) and non-splenectomized (71%). A significantassociation was found between the risk of infection and splenec-tomy in thalassemic patients (OR=3.8;CI=2.2;6.62; P=0.000). As-sociation between time after splenectomy and frequency of com-mon cold in thalassemia was significant (OR=2.85;CI=1.16;7.14;P=0.011). Severe infection and acute diarrhea were considerednot significantly different between the two groups.Conclusion Splenectomy in thalassemia can increase the sus-ceptibility of non-transfusion-transmitted mild infection. Furtherstudy is needed to elaborate this finding

scholarly journals Venetoclax and Decitabine Show Robust Activity in Advanced Systemic Mastocytosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Tahani Atieh ◽  
Janet Woodroof ◽  
Abdulraheem Yacoub
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Systemic Mastocytosis ◽  
Objective Response ◽  
Publicly Traded ◽  
First Line ◽  
Private Company ◽  
Allogenic Stem Cell Transplantation ◽  
Best Response ◽  
Kit D816v

Systemic mastocytosis (SM) is a heterogeneous group of diseases characterized by the proliferation of abnormal mast cells in the bone marrow or other organs. 1 Activating mutations in KIT are found in the majority of patients, with the KIT D816V mutation being the most common .2 While patients with indolent systemic mastocytosis (ISM) have a life-expectancy similar to the general population, approximately 40-53% of patients with SM have an associated hematologic neoplasm (SM-AHN) with a median overall survival of 2 years. 1-3 Treatment of SM-AHN is primarily directed at the AHN as this determines overall survival, with symptomatic treatment for SM if needed.4 Midostaurin is the only approved agent for SM with KIT K816V mutation and overall response rates in SM-AHN are &lt;60%. 5-6 No agents are approved beyond first line. We present the unique case of an 81-year-old male who presented with SM and low risk CMML (46 XY with ASXL1, KIT (p.D816V), SRSF2, TET2, RUNX1, MSH2, CBL). He received first line therapy with midostaurin 100 mg twice a day and achieved an early partial response but progressed after 7 months with increasing mastocytosis burden, rising tryptase and transformation of CMML to AML (image 1). He was subsequently treated with combination standard dose decitabine and venetoclax. The best response for the AML was CRi which was achieved after the first cycle and continues to be ongoing over 12 months since initiation of therapy. We also observed objective response of the SM disease burden on BM exams and steady decline in tryptase levels that continues to be ongoing (figure 1 and 2). Best response by IWG-MRT-ECNM is partial remission achieved after 9 months of therapy. SM-AML is rare and can be diagnosed concomitantly with SM or as a transformation of an SM-AHN. Additional mutations are often present, with the presence of ASXL1 and RUNX1 being associated with a particularly poor prognosis.7-8 Treatment for SM-AML is similar to standard AML treatment with allogenic stem cell transplantation (ASCT) being preferred in those able to tolerate it. While ASCT is the only potential cure for both diseases, SM often persists even with response of the AML.9-11 In a case report of 11 patients with SM-AML, 8 patients received induction chemotherapy with cytarabine and daunorubicin while 3 received induction with cytarabine and idarubicine. Seven patients received ASCT but five relapsed and eventually expired. None of the 3 long-term survivors had a c-KIT D816V mutation and two of them received ASCT. In 7 out of the 10 patients in CR or after ASCT, SM persisted. 9 In 2 case reports of SM-AML with D816V mutation, treatment consisted of induction and consolidation chemotherapy plus dasatinib and chemotherapy with ASCT and dasatinib. Both patients achieved HCR but again had persistent SM.10-11 The activity of hypomethylating agents (HMA) with venetoclax has not previously been reported in patients with SM-AML. Venetoclax plus either HMAs or low-dose cytarabine was approved for the treatment of AML in the elderly and those unable to tolerate induction chemotherapy in 2018. Venetoclax is an oral inhibitor of BCL-2, an antiapoptotic protein important in the pathophysiology of AML. In the initial study, the CR/Cri rate was 68% with a median time to response of 1.2 cycles. Venetoclax has also shown activity in other hematologic malignancies, including chronic lymphocytic leukemia, and non-Hodgkin's lymphoma.12 SM-AML is an aggressive disease with limited treatment options. To our knowledge, this is the first report of sustained response of both SM-AHN and AML using a HMA and venetoclax. Given the difference in response time and dynamics, this treatment combination seems to have activity in both disease clones independently. This case suggests a potential treatment option for this unmet need and demonstrates the importance of research into the utility of venetoclax in mast cell neoplasms. Disclosures Yacoub: Ardelyx: Current equity holder in publicly-traded company; Dynavax: Current equity holder in publicly-traded company; Cara Therapeutics: Current equity holder in publicly-traded company; Hylapharm: Current equity holder in private company; Incyte: Speakers Bureau; Agios: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support.

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