scholarly journals Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines

2021 ◽  
Author(s):  
Theron Gilliland ◽  
Yanan Liu ◽  
Rong Li ◽  
Matthew Dunn ◽  
Emily Cottle ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Rapid Evolution ◽  
Clinical Signs ◽  
In Vivo Studies ◽  
Hamster Model ◽  
S Protein ◽  
Neutralizing Capacity ◽  
Polyclonal Igg

Pandemic SARS CoV-2 has been undergoing rapid evolution during spread throughout the world resulting in the emergence of many Spike protein variants, some of which appear to either evade antibody neutralization, transmit more efficiently, or potentially exhibit increased virulence. This raises significant concerns regarding the long-term efficacy of protection elicited after primary infection and/or from vaccines derived from single virus Spike (S) genotypes, as well as the efficacy of anti-S monoclonal antibody based therapeutics. Here, we used fully human polyclonal human IgG (SAB-185), derived from hyperimmunization of transchromosomic bovines with DNA plasmids encoding the SARS-CoV-2 Wa-1 strain S protein or purified ectodomain of S protein, to examine the neutralizing capacity of SAB-185 in vitro and the protective efficacy of passive SAB-185 antibody (Ab) transfer in vivo. The Ab preparation was tested for neutralization against five variant SARS-CoV-2 strains: Munich (Spike D614G), UK (B.1.1.7), Brazil (P.1) and SA (B.1.3.5) variants, and a variant isolated from a chronically infected immunocompromised patient (Spike del144-146). For the in vivo studies, we used a new human ACE2 (hACE2) transgenic Syrian hamster model that exhibits lethality after SARS-Cov-2 challenge and the Munich, UK, SA and del144-146 variants. SAB-185 neutralized each of the SARS-CoV-2 strains equivalently on Vero E6 cells, however, a control convalescent human serum sample was less effective at neutralizing the SA variant. In the hamster model, prophylactic SAB-185 treatment protected the hamsters from fatal disease and minimized clinical signs of infection. These results suggest that SAB-185 may be an effective treatment for patients infected with SARS CoV-2 variants.

scholarly journals Preclinical Immuno-recognition and Neutralization of Lethality Assessment of a New Polyvalent Antivenom, VINS Snake Venom Antiserum – African IHS®, against Envenomation of Ten African Viperid and Elapid Snakes

2021 ◽  
pp. 25-43
Author(s):  
Djameh, Georgina I. ◽  
Nyarko, Samuel ◽  
Tetteh-Tsifoanya, Mark ◽  
Marfo, Frances M. ◽  
Adjei, Samuel ◽  
...  
Keyword(s):  
Snake Venom ◽  
Sub Saharan Africa ◽  
In Vivo Studies ◽  
Health Concern ◽  
Major Protein ◽  
Snake Species ◽  
Neutralizing Capacity ◽  
Preclinical Efficacy

Snakebite envenomation is a major health concern in developing countries causing significant mortality and morbidity. With over 1.2 million cases annually caused by medically important snake species belonging to the two families Viperidae (Echis spp. and Bitis spp.) and Elapidae (Naja spp. and Dendroaspis spp.). Several antivenoms are being produced and distributed to western sub-Saharan Africa for treatment of envenomation with the absence of preclinical efficacy studies. The present study evaluated the preclinical efficacy of venoms from Echis leucogaster, Echis ocellatus, Bitis arietans, Bitis gabonica, Naja haje, Naja melanoleuca, Naja nigricollis, Dendroaspis jamesoni, Dendroaspis polylepis and Dendroaspis viridis against a polyvalent Snake Venom Antiserum - African IHS (lyophilised), manufactured by VINS Bioproducts Limited (Telangana, India). Our in vitro results showed that, the SVA- AIHS contains antibodies that are capable of recognizing and binding majority of protein components representative of all eight major protein families of venoms of the snake species tested by double immunodiffusion assay and confirmed by western blot. The venom antiserum exhibited high neutralization efficacy against all the viperid and elapid snake species venoms in in vivo studies and confirmed the manufacturer’s recommended neutralization capacity. This is clear evidence that the VINS polyvalent SVA-AIHS batch tested has strong neutralizing capacity and will be useful in treating envenoming by most African viperid and some elapid snake species.

scholarly journals Review of the speculative role of co-infections in Streptococcus suis-associated diseases in pigs

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Milan R. Obradovic ◽  
Mariela Segura ◽  
Joaquim Segalés ◽  
Marcelo Gottschalk
Keyword(s):  
Respiratory Disease ◽  
Clinical Signs ◽  
Streptococcus Suis ◽  
In Vivo Studies ◽  
Economic Losses ◽  
Upper Respiratory Tract ◽  
Associated Diseases ◽  
Virulent Strains

AbstractStreptococcus suis is one of the most important bacterial swine pathogens affecting post-weaned piglets, causing mainly meningitis, arthritis and sudden death. It not only results in severe economic losses but also raises concerns over animal welfare and antimicrobial resistance and remains an important zoonotic agent in some countries. The definition and diagnosis of S. suis-associated diseases can be complex. Should S. suis be considered a primary or secondary pathogen? The situation is further complicated when referring to respiratory disease, since the pathogen has historically been considered as a secondary pathogen within the porcine respiratory disease complex (PRDC). Is S. suis a respiratory or strictly systemic pathogen? S. suis is a normal inhabitant of the upper respiratory tract, and the presence of potentially virulent strains alone does not guarantee the appearance of clinical signs. Within this unclear context, it has been largely proposed that co-infection with some viral and bacterial pathogens can significantly influence the severity of S. suis-associated diseases and may be the key to understanding how the infection behaves in the field. In this review, we critically addressed studies reporting an epidemiological link (mixed infections or presence of more than one pathogen at the same time), as well as in vitro and in vivo studies of co-infection of S. suis with other pathogens and discussed their limitations and possibilities for improvement and proposed recommendations for future studies.

IN VITRO AND IN VIVO TOXICITY EVALUATION OF TRAPA BISPINOSA ROXB. STARCH

2021 ◽  
pp. 58-62
Author(s):  
SURADWADEE THUNGMUNGMEE ◽  
NAKUNTWALAI WISIDSRI
Keyword(s):  
Lethal Dose ◽  
Clinical Signs ◽  
Fibroblast Cell ◽  
In Vivo Studies ◽  
Oral Toxicity ◽  
Cosmetic Ingredients ◽  
Nih 3T3 ◽  
Fibroblast Cell Lines

Objective: This study aimed to assess the toxicity of Trapa bispinosa Roxb. starch (TBS) through in vitro and in vivo studies.Methods: The cytotoxicity of TBS extract (TBSE) was evaluated on RAW 264.7 macrophage and NIH 3T3 fibroblast cell lines and the acute dermal andoral toxicities of TBS were analyzed in rats. To access acute dermal toxicity, the rats received a single application of 200, 1000, and 2000 mg/kg BW ofTBS, while for acute oral toxicity, the rats received a single administration of 300 and 2000 mg/kg BW of TBS. All animals were observed for changesin body weight, mortality, and clinical signs of abnormality after application and administration of the TBS.Results: The in vitro results showed that TBSE at concentrations of 6.25–200 μg/ml was non-cytotoxic to macrophages and fibroblasts. From acutetoxicity studies, the lethal dose of TBS was considered to be over 2000 mg/kg BW. No mortality, clinical signs of abnormality, or gross pathology weredetected at necropsy.Conclusion: TBS is non-toxic in in vitro and in vivo studies. Therefore, TBS can be used as pharmaceuticals excipients or cosmetic ingredients.

scholarly journals Protective Effects of STI-2020 Antibody Delivered Post-Infection by the Intranasal or Intravenous Route in a Syrian Golden Hamster COVID-19 Model

2020 ◽  
Author(s):  
Yanwen Fu ◽  
Junki Maruyama ◽  
Alok Singh ◽  
Reyna Lim ◽  
Arthur Ledesma ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Post Infection ◽  
Neutralizing Antibodies ◽  
In Vivo Studies ◽  
Intravenous Route ◽  
Protective Effects ◽  
Antibody Treatment ◽  
Hamster Model

ABSTRACTWe have previously reported that the SARS-CoV-2 neutralizing antibody, STI-2020, potently inhibits cytopathic effects of infection by genetically diverse clinical SARS-CoV-2 pandemic isolates in vitro, and has demonstrated efficacy in a hamster model of COVID-19 when administered by the intravenous route immediately following infection. We now have extended our in vivo studies of STI-2020 to include disease treatment efficacy, profiling of biodistribution of STI-2020 in mice when antibody is delivered intranasally (IN) or intravenously (IV), as well as pharmacokinetics in mice following IN antibody administration. Importantly, SARS-CoV-2-infected hamsters were treated with STI-2020 using these routes, and treatment effects on severity and duration of COVID-19-like disease in this model were evaluated. In SARS-CoV-2 infected hamsters, treatment with STI-2020 12 hours post-infection using the IN route led to a decrease in severity of clinical disease signs and a more robust recovery during 9 days of infection as compared to animals treated with an isotype control antibody. Treatment via the IV route using the same dose and timing regimen resulted in a decrease in the average number of consecutive days that infected animals experienced weight loss, shortening the duration of disease and allowing recovery to begin more rapidly in STI-2020 treated animals. Following IN administration in mice, STI-2020 was detected within 10 minutes in both lung tissue and lung lavage. The half-life of STI-2020 in lung tissue is approximately 25 hours. We are currently investigating the minimum effective dose of IN-delivered STI-2020 in the hamster model as well as establishing the relative benefit of delivering neutralizing antibodies by both IV and IN routes.

scholarly journals Peptide Platform as a Powerful Tool in the Fight against COVID-19

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1667
Author(s):  
Michela Murdocca ◽  
Gennaro Citro ◽  
Isabella Romeo ◽  
Antonio Lupia ◽  
Shane Miersch ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Antigenic Site ◽  
Protein Docking ◽  
In Vivo Studies ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Global Pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic causing over 195 million infections and more than 4 million fatalities as of July 2021.To date, it has been demonstrated that a number of mutations in the spike glycoprotein (S protein) of SARS-CoV-2 variants of concern abrogate or reduce the neutralization potency of several therapeutic antibodies and vaccine-elicited antibodies. Therefore, the development of additional vaccine platforms with improved supply and logistic profile remains a pressing need. In this work, we have validated the applicability of a peptide-based strategy focused on a preventive as well as a therapeutic purpose. On the basis of the involvement of the dipeptidyl peptidase 4 (DPP4), in addition to the angiotensin converting enzyme 2 (ACE2) receptor in the mechanism of virus entry, we analyzed peptides bearing DPP4 sequences by protein–protein docking and assessed their ability to block pseudovirus infection in vitro. In parallel, we have selected and synthetized peptide sequences located within the highly conserved receptor-binding domain (RBD) of the S protein, and we found that RBD-based vaccines could better promote elicitation of high titers of neutralizing antibodies specific against the regions of interest, as confirmed by immunoinformatic methodologies and in vivo studies. These findings unveil a key antigenic site targeted by broadly neutralizing antibodies and pave the way to the design of pan-coronavirus vaccines.

In vitro and in vivo studies of new cationic Zn(II)‐benzonaphthoporphyrazines as photosensitizers for PDT

2001 ◽  
Vol 5 (8) ◽  
pp. 645-651
Author(s):  
M. Peeva ◽  
M. Shopova ◽  
U. Michelsen ◽  
D. Wöhrle ◽  
G. Petrov ◽  
...  
Keyword(s):  
In Vivo Studies

Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Activation ◽  
In Vivo Studies ◽  
Blood Flow Response ◽  
Flow Response

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Effectiveness of the integration of quercetin, turmeric, and N-acetylcysteine in reducing inflammation and pain associated with endometriosis. In-vitro and in-vivo studies

2020 ◽  
Vol 72 (5) ◽  
Author(s):  
Mario Fadin ◽  
Maria C. Nicoletti ◽  
Marzia Pellizzato ◽  
Manuela Accardi ◽  
Maria G. Baietti ◽  
...  
Keyword(s):  
In Vivo Studies
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