scholarly journals Low Environmental Temperature Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Golden Syrian Hamsters

2021 ◽  
Author(s):  
Jasper Fuk-Woo Chan ◽  
Vincent Kwok-Man Poon ◽  
Chris Chung-Sing Chan ◽  
Kenn Ka-Heng Chik ◽  
Jessica Oi-Ling Tsang ◽  
...  
Keyword(s):  
Low Temperature ◽  
Disease Severity ◽  
Environmental Temperature ◽  
Neutralizing Antibody ◽  
Inflammatory Infiltration ◽  
Live Virus ◽  
Virus Shedding ◽  
Gene Copies ◽  
Temperature Group

Abstract Background The effect of low environmental temperature on viral shedding and disease severity of COVID-19 is uncertain. Methods We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21 oC), low (12-15 oC), and high (30-33 oC) temperature after challenge by 10 5 plaque-forming units of SARS-CoV-2. Results The nasal turbinate, trachea, and lung viral load and live virus titre were significantly higher (~0.5-log10 gene copies/β-actin, p<0.05) in the low temperature group at 7 days post-infection (dpi). The low temperature group also demonstrated significantly higher level of TNF-α, IFN-γ, IL-1β, and CCL3, and lower level of the antiviral IFN-α in lung tissues at 4dpi than the other two groups. Their lungs were grossly and diffusely haemorrhagic, with more severe and diffuse alveolar and peribronchiolar inflammatory infiltration, bronchial epithelial cell death, and significantly higher mean total lung histology scores. By 7dpi, the low temperature group still showed persistent and severe alveolar inflammation and haemorrhage, and little alveolar cell proliferative changes of recovery. The viral loads in the oral swabs of the low temperature group were significantly higher from 10-17dpi by about 0.5-1.0-log10 gene copies/β-actin. The mean neutralizing antibody titre of the low temperature group was significantly (p<0.05) lower than that of the room temperature group at 7dpi and 30dpi. Conclusions This study provided in-vivo evidence that low environmental temperature exacerbated the degree of virus shedding, disease severity, and tissue proinflammatory cytokines/chemokines expression, and suppressed the neutralizing antibody response of SARS-CoV-2-infected hamsters. Keeping warm in winter may reduce the severity of COVID-19.

Imidazolidinyl urea activates mast cells via MRGPRX2 to induce non-histaminergic allergy

2021 ◽  
Author(s):  
Jiapan Gao ◽  
Delu Che ◽  
Xueshan Du ◽  
Yi Zheng ◽  
Huiling Jing ◽  
...  
Keyword(s):  
Contact Dermatitis ◽  
Mast Cells ◽  
Pharmaceutical Products ◽  
Drug Induced ◽  
Inflammatory Infiltration ◽  
Local Inflammatory Response ◽  
Allergic Contact ◽  
G Protein Coupled

Abstract Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.

scholarly journals Design and Characterization of a DNA Vaccine Based on Spike with Consensus Nucleotide Sequence against Infectious Bronchitis Virus

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 50
Author(s):  
Lei Zuo ◽  
Wenjun Yan ◽  
Zhou Song ◽  
Hao Li ◽  
Xin Xie ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Dna Vaccine ◽  
Infectious Bronchitis Virus ◽  
Neutralizing Antibody ◽  
Economic Losses ◽  
Post Translational Modification ◽  
Virus Shedding ◽  
Infectious Bronchitis ◽  
Specific Pathogen ◽  
Cellular Immune

Avian coronavirus infectious bronchitis virus (IBV) causes severe economic losses in the poultry industry, but its control is hampered by the continuous emergence of new genotypes and the lack of cross-protection among different IBV genotypes. We designed a new immunogen based on a spike with the consensus nucleotide sequence (S_con) that may overcome the extraordinary genetic diversity of IBV. S_con was cloned into a pVAX1 vector to form a new IBV DNA vaccine, pV-S_con. pV-S_con could be correctly expressed in HD11 cells with corresponding post-translational modification, and induced a neutralizing antibody response to the Vero-cell-adapted IBV strain Beaudette (p65) in mice. To further evaluate its immunogenicity, specific-pathogen-free (SPF) chickens were immunized with the pV-S_con plasmid and compared with the control pVAX1 vector and the H120 vaccine. Detection of IBV-specific antibodies and cell cytokines (IL-4 and IFN-γ) indicated that vaccination with pV-S_con efficiently induced both humoral and cellular immune responses. After challenge with the heterologous strain M41, virus shedding and virus loading in tissues was significantly reduced both by pV-S_con and its homologous vaccine H120. Thus, pV-S_con is a promising vaccine candidate for IBV, and the consensus approach is an appealing method for vaccine design in viruses with high variability.

scholarly journals Improving the Biocontrol Potential of Bacterial Antagonists with Salicylic Acid against Brown Rot Disease and Impact on Nectarine Fruits Quality

Agronomy ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 209
Author(s):  
Nadia Lyousfi ◽  
Rachid Lahlali ◽  
Chaimaa Letrib ◽  
Zineb Belabess ◽  
Rachida Ouaabou ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Disease Severity ◽  
Mycelial Growth ◽  
Brown Rot ◽  
Antagonistic Bacteria ◽  
Biological Treatments ◽  
Rot Disease ◽  
The Impact

The main objective of this study was to evaluate the ability of both antagonistic bacteria Bacillus amyloliquefaciens (SF14) and Alcaligenes faecalis (ACBC1) used in combination with salicylic acid (SA) to effectively control brown rot disease caused by Monilinia fructigena. Four concentrations of salicylic acid (0.5%, 2%, 3.5%, and 5%) were tested under in vitro and in vivo conditions. Furthermore, the impact of biological treatments on nectarine fruit parameters’ quality, in particular, weight loss, titratable acidity, and soluble solids content, was evaluated. Regardless of the bacterium, the results indicated that all combined treatments displayed a strong inhibitory effect on the mycelial growth of M. fructigena and disease severity. Interestingly, all SA concentrations significantly improved the biocontrol activity of each antagonist. The mycelial growth inhibition rate ranged from 9.79% to 88.02% with the highest reduction rate recorded for bacterial antagonists in combination with SA at both concentrations of 0.5% and 3.5%. The in vivo results confirmed the in vitro results with a disease severity varying from 0.00% to 51.91%. A significant biocontrol improvement was obtained with both antagonistic bacteria when used in combination with SA at concentrations of 0.5% and 2%. The lowest disease severity observed with ACBC1 compared with SF14 is likely due to a rapid adaptation and increase of antagonistic bacteria population in wounded sites. The impact of all biological treatments revealed moderate significant changes in the fruit quality parameters with weight loss for several treatments. These results suggest that the improved disease control of both antagonistic bacteria was more likely directly linked to both the inhibitory effects of SA on pathogen growth and induced fruit resistance.

scholarly journals SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nanda Kishore Routhu ◽  
Narayanaiah Cheedarla ◽  
Venkata Satish Bollimpelli ◽  
Sailaja Gangadhara ◽  
Venkata Viswanadh Edara ◽  
...  
Keyword(s):  
Antibody Response ◽  
Antibody Titer ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Significant Loss ◽  
Lung Pathology ◽  
Live Virus ◽  
Suitable Candidate ◽  
Immune Pathology

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

scholarly journals Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yongbing Pan ◽  
Jianhui Du ◽  
Jia Liu ◽  
Hai Wu ◽  
Fang Gui ◽  
...  
Keyword(s):  
Phage Display ◽  
Neutralizing Antibodies ◽  
Variable Region ◽  
Neutralizing Antibody ◽  
Chain Gene ◽  
Prophylactic Efficacy ◽  
Heavy Chains ◽  
Effective Interventions ◽  
Phage Display Libraries

AbstractAs the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

In vivo degradation of low temperature calcium and magnesium phosphate ceramics in a heterotopic model

2011 ◽  
Vol 7 (9) ◽  
pp. 3469-3475 ◽  
Author(s):  
Uwe Klammert ◽  
Anita Ignatius ◽  
Uwe Wolfram ◽  
Tobias Reuther ◽  
Uwe Gbureck
Keyword(s):  
Low Temperature ◽  
Magnesium Phosphate ◽  
Calcium And Magnesium ◽  
In Vivo Degradation

scholarly journals Lactobacillus johnsonii La1 Attenuates Helicobacter pylori-Associated Gastritis and Reduces Levels of Proinflammatory Chemokines in C57BL/6 Mice

2005 ◽  
Vol 12 (12) ◽  
pp. 1378-1386 ◽  
Author(s):  
Dionyssios N. Sgouras ◽  
Effrosini G. Panayotopoulou ◽  
Beatriz Martinez-Gonzalez ◽  
Kalliopi Petraki ◽  
Spyros Michopoulos ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Lamina Propria ◽  
Serum Levels ◽  
Favorable Effect ◽  
Lactobacillus Johnsonii ◽  
Ags Cells ◽  
Inflammatory Infiltration ◽  
H Pylori

ABSTRACT In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P = 0.038) and neutrophilic (P = 0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P = 0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P = 0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.

scholarly journals Priming with tat-Deleted Caprine Arthritis Encephalitis Virus (CAEV) Proviral DNA or Live Virus Protects Goats from Challenge with Pathogenic CAEV

1998 ◽  
Vol 72 (8) ◽  
pp. 6796-6804 ◽  
Author(s):  
Abdallah Harmache ◽  
Christian Vitu ◽  
François Guiguen ◽  
Pierre Russo ◽  
Giuseppe Bertoni ◽  
...  
Keyword(s):  
Virus Isolation ◽  
Encephalitis Virus ◽  
Wild Type Virus ◽  
Infection Model ◽  
Wild Type ◽  
Live Virus ◽  
Caprine Arthritis Encephalitis Virus ◽  
Proviral Dna ◽  
Homologous Virus

ABSTRACT We previously reported that infection of goats with caprine arthritis encephalitis virus (CAEV) tat− proviral DNA or virus results in persistent infection, since the animals seroconverted and direct virus isolation from cultures of blood-derived macrophages was positive. In this study we wanted to determine whether goats injected with CAEV tat− proviral DNA or virus were protected against challenge with the pathogenic homologous virus and to investigate whether CAEV tat− was still pathogenic. All animals injected with CAEV tat− became infected as indicated by seroconversion and virus isolation. Challenge at 8 or 9 months postinfection demonstrated protection in four of four animals injected with CAEV tat− but did not in three of three mock-inoculated challenged goats. Challenge virus was undetectable in the blood macrophages of protected animals during a period of 6 or 10 months postchallenge. In two of four protected animals, however, we were able to detect the challenge wild-type virus by reverse transcriptase PCR on RNA directly extracted from synovial membrane cells surrounding the inoculation site. This result suggests that protection was achieved without complete sterilizing immunity. Animals injected with CAEV tat− and mock challenged developed inflammatory lesions in the joints, although these lesions were not as severe as those in CAEV wild-type-injected goats. These results confirm the dispensable role of Tat in CAEV replication in vivo for the establishment of infection and pathogenesis and demonstrate in another lentivirus infection model the efficacy of live attenuated viruses to induce resistance to superinfection.

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