scholarly journals Effectiveness of ACB-IP 1.0 Universal Pathogen Free Concentrated Cocktail Convalescent Plasma in COVID-19 Infection

2021 ◽  
Author(s):  
Cansu Hemsinlioglu ◽  
Nil Banu Pelit ◽  
Koray Yalcin ◽  
Omur Selin Gunaydin ◽  
Nihal Ozturk Sahin ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Activity ◽  
Application Time ◽  
Infection Transmission ◽  
Single Donor ◽  
Registration Number ◽  
Antibody Titers ◽  
Registration Date ◽  
Length Of Hospitalization ◽  
Donor Plasma

Abstract BACKGROUNDThe efficacy of SARS-CoV2 single donor convalescent plasma (CP) varied according to the application time and the amount of antibody that is administered. Single donor CP has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the safety and efficacy of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled CP product was investigated. MATERIALS AND METHODSA total of sixteen patients were treated with either single donor CP (N:9) or pathogen-free, concentrated, pooled CP (ACB-IP 1.0) (N:7).RESULTSFive out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor CP. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor CP (0.9642) in 1:256 dilution (ρ<0.01)The mortality rates of the patients treated with ACB-IP 1.0 plasma were statistically lower (p< 0.05) than the patients treated with single donor CP. The administration of either single donor CP or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization (ρ< 0.01).CONCLUSIONThe present study established ACB-IP 1.0 plasma product as a safe and potentially effective treatment for COVID-19, allowing rapid access to patients in need.TRIAL REGISTRATIONTrial Registration Number: NCT04769245Trial Registration Date: 17.03.2021

scholarly journals THE EFFECTIVENESS OF ACB-IP 1.0 UNIVERSAL PATHOGEN FREE CONCENTRATED COCKTAIL CONVALESCENT PLASMA IN COVID-19 INFECTION

2021 ◽  
Author(s):  
Cansu Hemsinlioglu ◽  
Nil Banu Pelit ◽  
Koray Yalcin ◽  
Omur Selin Gunaydin ◽  
Nihal Ozturk Sahin ◽  
...  
Keyword(s):  
Blood Group ◽  
Neutralizing Antibody ◽  
Antibody Activity ◽  
Efficacy And Safety ◽  
Pathogen Inactivation ◽  
Single Donor ◽  
Antibody Titers ◽  
Length Of Hospitalization ◽  
Plasma Characteristic ◽  
Donor Plasma

Abstract Introduction The efficacy of SARS-CoV2 standard single donor convalescent plasma varied according to the application time and most importantly the amount of antibody that is administered. Single donor plasma has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the efficacy and safety of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled convalescent plasma was investigated. Methods In this study, ACB-IP 1.0 convalescent plasma product was prepared as follows; first, convalescent plasma was collected from different donors, then pathogen-inactivation was carried-out, and isohemagglutinins were cryodepleted, respectively. Finally, concentrated convalescent plasma product was pooled and stored until use. A total of sixteen patients were treated with two different convalescent plasma products. Nine patients were treated with standard single donor convalescent plasma and seven were treated with pathogen-free, concentrated, pooled convalescent plasma (ACB-IP 1.0) between 01 March 2020 and 31 December 2020. The outcomes of these two plasma products were compared regarding SARS-CoV2 antibody titers, neutralizing antibody activities, length of hospitalization and mortality rates. Results Five out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor plasma. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor plasma (0.9642) in 1:256 dilution (ρ=0.0087) The mortality rate of the patients treated with ACB-IP 1.0 plasma showed statistically lower (p: 0,033) than the patients treated with single donor plasma. The administration of either single donor plasma or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization compared to administration of either plasma to the patients later than eight days (ρ= 0,0021) Discussion Pathogen-free, concentrated, pooled convalescent plasma may resolve the bias in SARS-CoV2 antibody titers and neutralizing antibody activities, without requiring blood group compatibility that allows patient accessibility in a shorter time and has safe plasma characteristic. This study indicates that ACB-IP 1.0 may be a superior product compared to standard single donor plasma.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers in Convalescent Plasma and Recipients in New Mexico: An Open Treatment Study in Patients With Coronavirus Disease 2019

2020 ◽  
Vol 222 (10) ◽  
pp. 1620-1628 ◽  
Author(s):  
Steven B Bradfute ◽  
Ivy Hurwitz ◽  
Alexandra V Yingling ◽  
Chunyan Ye ◽  
Qiuying Cheng ◽  
...  
Keyword(s):  
New Mexico ◽  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibody ◽  
Traditional Food ◽  
Neutralizing Activity ◽  
Time Points ◽  
Before And After ◽  
Open Treatment ◽  
Antibody Titers ◽  
Donor Plasma

Abstract Background Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway. Methods We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Results NAb titers in the donor CP units were low (&lt;1:40 to 1:160) and had no effect on recipient neutralizing activity 1 day after transfusion. NAb titers were detected in 6 of 12 patients on enrollment and in 11 of 12 at ≥2 time points. Average titers peaked on day 7 and declined toward day 14 (P = .004). Nab titers and immunoglobulin G levels were correlated in donor plasma units (ρ = 0.938; P &lt; .001) and in the cumulative patient measures (ρ = 0.781; P &lt; .001). Conclusions CP infusion did not alter recipient NAb titers. Prescreening of CP may be necessary for selecting donors with high titers of neutralizing activity for infusion into patients with COVID-19. Clinical Trials Registration NCT04434131.

scholarly journals Application of an Endothelial Cell Culture Assay for the Detection of Neutralizing Anti-Clostridium Perfringens Beta-Toxin Antibodies in a Porcine Vaccination Trial

Toxins ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 225 ◽  
Author(s):  
Olivia K. Richard ◽  
Sven Springer ◽  
Jacqueline Finzel ◽  
Tobias Theuß ◽  
Marianne Wyder ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Clostridium Perfringens ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Antibody Activity ◽  
Antibody Titers ◽  
Type C ◽  
Cell Culture Assay ◽  
Beta Toxin

Background: Beta-toxin (CPB) is the major virulence factor of Clostridium perfringens type C, causing hemorrhagic enteritis in newborn pigs but also other animals and humans. Vaccines containing inactivated CPB are known to induce protective antibody titers in sow colostrum and neutralization of the CPB activity is thought to be essential for protective immunity in newborn piglets. However, no method is available to quantify the neutralizing effect of vaccine-induced antibody titers in pigs. (2) Methods: We developed a novel assay for the quantification of neutralizing anti-CPB antibodies. Sera and colostrum of sows immunized with a commercial C. perfringens type A and C vaccine was used to determine neutralizing effects on CPB induced cytotoxicity in endothelial cells. Antibody titers of sows and their piglets were determined and compared to results obtained by an ELISA. (3) Results: Vaccinated sows developed neutralizing antibodies against CPB in serum and colostrum. Multiparous sows developed higher serum and colostrum antibody titers after booster vaccinations than uniparous sows. The antibody titers of sows and those of their piglets correlated highly. Piglets from vaccinated sows were protected against intraperitoneal challenge with C. perfringens type C supernatant. (4) Conclusions: The test based on primary porcine endothelial cells quantifies neutralizing antibody activity in serum and colostrum of vaccinated sows and could be used to reduce and refine animal experimentation during vaccine development.

scholarly journals Estimates of reduced vaccine effectiveness against hospitalization, infection, transmission and symptomatic disease of a new SARS-CoV-2 variant, Omicron (B.1.1.529), using neutralizing antibody titers

2021 ◽  
Author(s):  
Billy J Gardner ◽  
A. Marm Kilpatrick
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Vaccine Effectiveness ◽  
Vaccine Protection ◽  
Infection Transmission ◽  
Symptomatic Disease ◽  
Antibody Titers ◽  
Protection Against Infection

The emergence of the Omicron variant (B.1.1.529) of SARS-CoV-2 has raised concerns about how mutations in the spike protein might influence immune escape and vaccine protection against infection and disease, COVID-19. Initial estimates of immune escape measure neutralizing antibody titers, which have been shown to be a correlate of protection for COVID-19, but vary among studies. However, no studies have examined variation in vaccine effectiveness (VE) using estimated reductions in neutralizing antibody titers across virus variants. We quantified consistency in relative neutralizing antibody titers across studies. We then examined relationships between variant-specific reductions in neutralizing antibodies and protection against documented infection, symptomatic disease, and hospitalizations across variants and vaccines. We found considerable variation in variant-specific neutralizing antibody titers between studies, but within-study comparisons across variants were far more robust. There was insufficient data to estimate VE for a single vaccine across variants, especially for higher levels of immune evasion (>7-fold reductions in neutralizing antibody titers) observed with the Omicron variant (40-fold). Instead, we leveraged variation among both vaccines and virus variants to estimate VE - neutralizing antibody titer relationships across a 30 to 100-fold range of neutralizing antibody titers reduction. Omicron increased the risk of hospitalization four to five-fold and increased the risk of symptomatic disease seven to ten-fold for mRNA vaccinees, with similar relative effects for recently vaccinated, or individuals with waned antibody titers. Third doses restored titers and protection to levels similar to waned immunity against Delta. Overall, these analyses indicate that vaccine effectiveness against severe disease is significantly diminished for waned individuals, and protection against infection, symptomatic disease and transmission is nearly eliminated. However, third doses significantly ameliorate these reductions but only restore protection to levels equivalent to waned protection against the Delta variant. The invasion of Omicron is likely to result in widespread infection, and substantial hospitalizations unless widespread boosting of immunity occurs.

scholarly journals Heterologous prime-boost vaccination with ChAdOx1 nCoV-19 and BNT162b2 mRNA

2021 ◽  
Author(s):  
Matthias Tenbusch ◽  
Sofie Schumacher ◽  
Emanuel Vogel ◽  
Alina Priller ◽  
Juergen Held ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Antibody Activity ◽  
Immune Protection ◽  
Precautionary Measure ◽  
Antibody Testing ◽  
Boost Vaccination ◽  
Vaccination Scheme ◽  
Antibody Titers ◽  
Antibody Levels

Administration of a first dose of the COVID-19 vaccine ChAdOx1 nCoV-19 (Vaxzevria®, AstraZeneca) is associated with a certain risk for vaccine-induced immune thrombotic thrombocytopenia. Therefore, several countries have recommended replacing the second dose of ChAdOx1 nCoV-19 with an mRNA-based vaccine as a precautionary measure, although data on safety and efficacy of such heterologous prime-boost regimen are sparse. Therefore, vaccinees, who had received a heterologous vaccination using ChAdOx1 nCoV-19 as prime and BNT162b2 (Comirnaty®, BioNTech-Pfizer) mRNA as boost vaccination were offered SARS-CoV-2 antibody testing to quantify their vaccine-induced neutralizing antibody response. The results were compared to cohorts of healthcare workers or volunteers, who received homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination regimens, respectively. A striking increase of vaccine-induced SARS-CoV-2 neutralizing antibody activity was observed in 229 vaccinees that received a BNT162b2 boost 9 to 12 weeks after ChAdOx1 nCoV-19 prime. In our cohort comprising over 480 individuals, the heterologous vaccination scheme induced significantly higher neutralizing antibody titers than homologous ChAdOx1 nCoV-19 and even than homologous BNT162b2 vaccination. This proves that a single dose of a COVID-19 mRNA vaccine after ChAdOx1 nCoV-19 prime vaccination is sufficient to achieve high neutralizing antibody levels predicting immune protection from SARS-CoV-2 infection, and may even increase vaccine efficacy offering an alternative in a setting of vaccine shortage.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

scholarly journals Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study

2021 ◽  
Vol 10 (10) ◽  
pp. 2113
Author(s):  
Mohamed Abuzakouk ◽  
Khaled Saleh ◽  
Manuel Algora ◽  
Ahmad Nusair ◽  
Jawahir Alameri ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Clinical Improvement ◽  
Primary Outcome ◽  
Neutralizing Antibody ◽  
Limited Data ◽  
Inverse Probability Weights ◽  
Single Center Study ◽  
Life Threatening ◽  
Antibody Titers ◽  
Disease Severity Scale

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods: A retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3) Results: Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP; among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41–1.37), p = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23–1.22), p = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (−0.14 days (95% CI: −3.19–2.91 days), p = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, p = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.

scholarly journals Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1347
Author(s):  
Claudia Maria Trombetta ◽  
Serena Marchi ◽  
Simonetta Viviani ◽  
Alessandro Manenti ◽  
Linda Benincasa ◽  
...  
Keyword(s):  
Natural Infection ◽  
Neutralizing Antibody ◽  
Original Strain ◽  
Immune Protection ◽  
Serum Samples ◽  
Symptomatic Infection ◽  
Neutralizing Activity ◽  
The United Kingdom ◽  
Antibody Titers ◽  
Pandemic Wave

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

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