scholarly journals Effects of Potent Neutralizing Antibodies from Convalescent Plasma in Patients Hospitalized for Severe SARS-CoV-2 Infection.

2020 ◽  
Author(s):  
Arvind Gharbharan ◽  
Carlijn Jordans ◽  
Corine GeurtsvanKessel ◽  
Jan den Hollander ◽  
Faiz Karim ◽  
...  
Keyword(s):  
Plasma Treatment ◽  
Neutralizing Antibodies ◽  
Clinical Course ◽  
Humoral Response ◽  
Disease Course ◽  
Course Of Disease ◽  
Future Studies ◽  
Immunological Responses ◽  
Translational Approach

Abstract Convalescent plasma could be an inexpensive and widely available treatment for COVID-19 patients but reports on effectiveness are inconclusive. We collected convalescent plasma from donors with high titers of neutralizing anti-SARS-CoV-2 antibodies effectively blocking SARS-CoV-2 infection in vitro. In a randomized clinical trial of 86 COVID-19 patients, no overall clinical benefit of 300 mL convalescent plasma was found in patients hospitalized for COVID-19 in the Netherlands. Using a comprehensive translational approach, we unraveled the virological and immunological responses following plasma treatment which helps to understand which COVID-19 patients may benefit from this therapy and should be the focus of future studies. Convalescent plasma treatment in this patient group did not improve survival, had no effect on the clinical course of disease, nor did plasma enhance viral clearance in the respiratory tract, influence anti-SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. The vast majority of patients already had potent neutralizing anti-SARS-CoV-2 antibodies at hospital admission and at comparable titers as the carefully selected plasma donors. Together, these data indicate that the variable effectivity observed in trials on convalescent plasma for COVID-19 may be explained by the timing of treatment and varying levels of preexisting anti-SARS-CoV-2 immunity in patients. It also substantiates that convalescent plasma should be studied as early as possible in the disease course or at least preceding the start of an autologous humoral response. Trial registration: Clinicaltrials.gov: NCT04342182

scholarly journals Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Arvind Gharbharan ◽  
Carlijn C. E. Jordans ◽  
Corine GeurtsvanKessel ◽  
Jan G. den Hollander ◽  
Faiz Karim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Standard Care ◽  
Humoral Response ◽  
Viral Clearance ◽  
Disease Course ◽  
Future Studies ◽  
Immunological Responses ◽  
Translational Approach

AbstractIn a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.

scholarly journals Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France

2020 ◽  
Author(s):  
Samira Fafi-Kremer ◽  
Timothee Bruel ◽  
Yoann Madec ◽  
Rebecca Grant ◽  
Laura Tondeur ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Rapid Test ◽  
Humoral Response ◽  
Hospital Staff ◽  
Sample Collection ◽  
Future Studies ◽  
Neutralizing Activity ◽  
Neutralization Capacity ◽  
Mild Disease

Background: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized. Methods: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity).The neutralizing activity of the sera was tested with a pseudovirus-based assay. Results: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV- 2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P=0.02). Conclusion: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.

Induction of a Robust Humoral Response using HIV-1 VLPMPER-V3 as a Novel Candidate Vaccine in BALB/c Mice

2019 ◽  
Vol 17 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Fatemeh Tohidi ◽  
Seyed Mehdi Sadat ◽  
Azam Bolhassani ◽  
Ramin Yaghobi ◽  
Mona Sadat Larijani
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Humoral Response ◽  
Cellular Responses ◽  
Immunodeficiency Virus ◽  
Potential Vaccine ◽  
Humoral Responses ◽  
Hiv 1

Background: Several approaches have not been successful to suppress HIV (Human immunodeficiency virus) infection among infected individuals or to prevent it yet. In order to expand strong HIV specific humoral and cellular responses, Virus-like particles (VLPs) as potential vaccines show significant increase in neutralizing antibodies secretion, T-cell count and also secretion of cytokines. Objective: This study aimed at immunological evaluation of VLPs harboring high copy of MPERV3 in BALB/c mice. Methods: Female BALB/c mice were immunized with homologous and heterologous primeboosting regimens of HIV-1 VLPMPER-V3. Their immune responses were evaluated for humoral responses (Total IgG and IgG isotyping) and cellular responses (IFN-γ, IL-5 secretion, in vitro CTL assay and T cell proliferation) and compared in immunized mice. Results: The data showed robust induction of humoral response in mice groups which received different regimens of VLP. Furthermore, analysis of cytokine profile indicated that the highest IL-5 secretion was related to VLP+M50 group and confirmed the dominance of Th2 immunity in this group. Conclusion: This study showed that VLP MPER-V3 as a potential vaccine candidate has the potency as an effective prophylactic vaccine and this finding guarantees further investigations to achieve a promising HIV-1 vaccine candidate.

scholarly journals Issues beyond resistance: inadequate antibiotic therapy and bacterial hypervirulence

FEMS Microbes ◽  
2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Lee W Goneau ◽  
Johannes Delport ◽  
Luana Langlois ◽  
Susan M Poutanen ◽  
Hassan Razvi ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Clinical Significance ◽  
Clinical Course ◽  
Disease Course ◽  
Course Of Disease ◽  
Inadequate Antibiotic Therapy ◽  
Microbe Interactions ◽  
Persistence Factors ◽  
Selection Of

ABSTRACT The administration of antibiotics while critical for treatment, can be accompanied by potentially severe complications. These include toxicities associated with the drugs themselves, the selection of resistant organisms and depletion of endogenous host microbiota. In addition, antibiotics may be associated with less well-recognized complications arising through changes in the pathogens themselves. Growing evidence suggests that organisms exposed to antibiotics can respond by altering the expression of toxins, invasins and adhesins, as well as biofilm, resistance and persistence factors. The clinical significance of these changes continues to be explored; however, it is possible that treatment with antibiotics may inadvertently precipitate a worsening of the clinical course of disease. Efforts are needed to adjust or augment antibiotic therapy to prevent the transition of pathogens to hypervirulent states. Better understanding the role of antibiotic-microbe interactions and how these can influence disease course is critical given the implications on prescription guidelines and antimicrobial stewardship policies.

scholarly journals Antibody interference by a non-neutralizing antibody abrogates humoral protection against Plasmodium liver stage

2020 ◽  
Author(s):  
Kamalakannan Vijayan ◽  
Ramyavardhanee Chandrasekaran ◽  
Olesya Trakhimets ◽  
Samantha L. Brown ◽  
Nicholas Dambrauskas ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Liver Stage ◽  
Repeat Domain ◽  
Major Surface ◽  
Humoral Responses ◽  
Initial Results

AbstractBoth subunit and attenuated whole sporozoite vaccination strategies against Plasmodium infection have shown promising initial results in malaria-naïve westerners but exhibited less efficacy in malaria-exposed individuals in endemic areas. It has been hypothesized that preexisting immunity to malaria represents a significant roadblock to the development of a protective vaccine. Here, we demonstrate proof-of-concept that non-neutralizing antibodies (nNAb) can directly interfere with protective anti-PyCSP humoral responses. We developed and characterized a novel monoclonal antibody, RAM1, against the P. yoelii sporozoite major surface antigen, circumsporozoite protein (CSP). Unlike the canonical PyCSP repeat domain binding and neutralizing antibody (NAb) 2F6, RAM1 does not inhibit sporozoite traversal or entry of hepatocytes in vitro. Though 2F6 and RAM1 bind non-overlapping regions of the CSP-repeat domain, pretreatment with RAM1 abrogated 2F6’s capacity to block sporozoite traversal and invasion in vitro. Importantly, RAM1 reduced the efficacy of the polyclonal humoral response against CSP in vivo, paralleling the observed reduced efficacy of RTS,S in malaria-exposed populations. Taken together, our data demonstrate the interference of non-neutralizing antibodies with the efficacy of NAbs and may impact the efficacy of anti-CSP vaccines in malaria-exposed individuals.

scholarly journals RBD-IgG levels correlate with protection in Residents Facing SARS-CoV-2 B.1.1.7 Outbreaks

2021 ◽  
Author(s):  
Hubert Blain ◽  
Edouard Tuaillon ◽  
Lucie Gamon ◽  
Amandine Pisoni ◽  
Stephanie Miot ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Nasopharyngeal Swab ◽  
Receptor Binding Domain ◽  
Limited Information ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Neutralization Activity ◽  
Polymerase Chain

Background Limited information exists on nursing home (NH) residents regarding BNT162b2/Pfizer vaccine efficacy in preventing SARS-CoV-2 and severe Covid-19, and its association with post-vaccine humoral response. Methods 396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-PCR). SARS-CoV-2 Receptor-Binding Domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-PCR-positive residents, and serum neutralizing antibodies in vaccinated residents from one NH. Results The incidence of positive RT-PCR was lower in residents vaccinated by two doses (22.7%) vs one dose (32.3%) or non-vaccinated residents (43.7%)(p<0.01). Covid-19-induced deaths were observed in 10.4% of the non-vaccinated residents, in 6.4% of those who had received one dose, and in 0.9% with two doses (p=0.0007). Severe symptoms were more common in infected non-vaccinated (21.0%) vs vaccinated residents (47.6%, p=0.002). Higher levels of RBD-IgG (n=325) were associated with a lower SARS-CoV-2 incidence. No in vitro serum neutralization activity was found for RBD-IgG levels below 1,050 AU/mL. RBD-IgG levels were inversely associated with N-Ag levels, found as a risk factor of severe Covid-19. Conclusions Two BNT162b2/Pfizer doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. BNT162b2/Pfizer efficacy was partly predicted by post-vaccine RBD-IgG levels.

scholarly journals SARS-CoV-2-Specific Antibody Profiles Distinguish Patients with Moderate from Severe COVID-19

2020 ◽  
Author(s):  
Leire de Campos Mata ◽  
Janet Piñero ◽  
Sonia Tejedor Vaquero ◽  
Roser Tachó-Piñot ◽  
Maria Kuksin ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Clinical Course ◽  
Severe Disease ◽  
Serum Antibody ◽  
Gastrointestinal Symptoms ◽  
Humoral Response ◽  
Receptor Binding Domain ◽  
Protective Function ◽  
Immune Pathways ◽  
Humoral Responses

SummaryThe production of SARS-CoV-2-specific neutralizing antibodies is widely considered as a key mechanism for COVID-19 resolution and protection. However, beyond their protective function, antibodies to SARS-CoV-2 may also participate in disease pathogenesis. To explore the potential relationship between virus-specific humoral responses and COVID-19 immunopathology, we measured serum antibody classes and subclasses to the receptor-binding domain of the SARS-CoV-2 spike protein and the nucleoprotein in a cohort of hospitalized COVID-19 patients with moderate to severe disease. We found that RBD-specific IgG1 and IgG3 dominated the humoral response to SARS-CoV-2, were more abundant in severe patients, and positively correlated with several clinical parameters of inflammation. In contrast, a virus-specific IgA2 response skewed toward RBD rather than NP associated with a more favorable clinical course. Interestingly, RBD-dominant IgA2 responses were mostly detected in patients with gastrointestinal symptoms, suggesting the possible involvement of intrinsically tolerogenic gut immune pathways in the attenuation of virus-induced inflammation and disease resolution.

Multi-dimensional Visualisation of Laboratory Findings and Functional Test Results for Analysing the Clinical Course of Disease in Medicine

1995 ◽  
Vol 34 (03) ◽  
pp. 302-308 ◽  
Author(s):  
C. J. Luz ◽  
W. Giere ◽  
R. Lüdecke ◽  
D. Jonas ◽  
A. J. W. Goldschmidt
Keyword(s):  
Clinical Course ◽  
Test Results ◽  
Geometrical Figure ◽  
Laboratory Findings ◽  
Course Of Disease ◽  
Quantitative Examination ◽  
Ward Rounds ◽  
Patient’S History ◽  
Graphical Primitive ◽  
Computerized Medical Record

Abstract:The illustration of a patient’s history by a graphical primitive is discussed. Illustration technology is presented which simultaneously represents quantitative examination findings (e. g., laboratory values) and qualitative findings (e. g., from function diagnostics) by a single geometrical figure. Depending on the medical results, this figure takes on characteristic forms which can be identified as patterns typical for a specific disease. The procedure developed is integrated in a user interface which is implemented in the form of a computerized medical record for use on a pentop computer. This portable computer assists the physician during ward rounds, supplies additional, intelligence-based information, serves quality control, and streamlines working procedures making them more efficient.

scholarly journals A Bacterially-Expressed Recombinant Envelope Protein from Usutu Virus Induces Neutralizing Antibodies in Rabbits

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 157
Author(s):  
Kinga Böszörményi ◽  
Janet Hirsch ◽  
Gwendoline Kiemenyi Kayere ◽  
Zahra Fagrouch ◽  
Nicole Heijmans ◽  
...  
Keyword(s):  
Envelope Protein ◽  
Neutralizing Antibodies ◽  
Size Exclusion ◽  
Vitro Assay ◽  
Usutu Virus ◽  
Transmission Electron ◽  
Exclusion Chromatography ◽  
Efficacious Vaccine ◽  
Human Infections

Background: Recently, an emerging flavivirus, Usutu virus (USUV), has caused an epidemic among birds in Europe, resulting in a massive die-off in Eurasian blackbirds. Currently found only in Europe and Africa, it can be envisioned that Usutu virus will follow the path of other flaviviruses, like West Nile virus and Zika virus, and will spread via its mosquito vectors and bird hosts to other parts of the world. Several cases of human infections by Usutu virus have already been published. Anticipating this spread, development of an efficacious vaccine would be highly desirable. Method: This study describes the production in E. coli, purification, and refolding of a partial USUV envelope protein. Prior to immunization, the protein was characterized using size exclusion chromatography, transmission electron microscopy and dynamic light scattering, showing the limited presence of virus-like structures, indicating that the protein solution is probably a mixture of mono and multimeric envelope proteins. Results: Immunizations of two rabbits with the refolded E-protein fraction, mixed with a strong adjuvant, resulted in the generation of neutralizing antibodies, as evidenced in an in vitro assay. Discussion: The way forward towards a subunit vaccine against Usutu virus infection is discussed.

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