scholarly journals Designing multi-epitope based peptide vaccine targeting spike protein SARS-CoV-2 B1.1.529 (Omicron) variant using computational approaches.

2021 ◽  
Author(s):  
Meet Parmar ◽  
Ritik Thumar ◽  
Jigar Sheth ◽  
Dhaval Patel

Since the SARS-CoV-2 outbreak in 2019, millions of people have been infected with the virus, and due to its high human-to-human transmission rate, there is a need for a vaccine to protect people. Although some vaccines are in use, due to the high mutation rate in the SARS-CoV-2 multiple variants, the current vaccines may not be sufficient to immunize people against new variant threats. One of the emerging variants of concern is B1.1.529 (Omicron), which carries ~30 mutations in the Spike protein of SARS-CoV-2 is predicted to evade antibodies recognition even from vaccinated people. We used a structure-based approach along with an epitope prediction server to develop a Multi-Epitope based Subunit Vaccine (MESV) involving SARS-CoV-2 B1.1.529 variant spike glycoprotein. The predicted epitope with better antigenicity and non-toxicity were used for designing and predicting vaccine construct features and structure models. The MESV construct In-silico cloning in pET28a expression vector predicted the construct to be highly translational. The proposed MESV vaccine construct was also subjected to immune simulation prediction and was found to be highly antigenic and elicit a cell-mediated immune response. The proposed MESV in the present study has the potential to be evaluated further for vaccine production against the newly identified B1.1.529 (Omicron) variant of concern.

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1457
Author(s):  
Dewald Schoeman ◽  
Burtram C. Fielding

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.


npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
René Wintjens ◽  
Amanda Makha Bifani ◽  
Pablo Bifani

2019 ◽  
Vol 6 (4) ◽  
pp. 80 ◽  
Author(s):  
J. Hunter Rice ◽  
Margaret M. McDaniel ◽  
Alyson Holland ◽  
Shigetoshi Eda

Mycobacterium avium subspecies paratuberculosis (Map) causes chronic granulomatous disease in cattle and ruminant livestock, causing substantial economic losses. Current vaccines delay clinical signs but cannot train the immune system to fully eradicate latent Map. During latency, Map uses host defenses, cage-like macrophage clusters called granuloma, as incubators for months or years. We used an in vitro model to investigate the early coordination of macrophages into granuloma upon Map infection over ten days. We found that at multiplicities of infection (MOI; Map:macrophages) of 1:2 and below, the macrophages readily form clusters and evolve pro-inflammatory cytokines in keeping with a cell-mediated immune response. At higher MOIs, viability of host macrophages is negatively impacted. At 1:4 MOI, we quantified viable Map in our model and confirmed that intracellular Map reproduced over the first five days of infection. Host cells expressed Type 1-specific cytokines, and Map-infected macrophages displayed reduced motility compared to Map-exposed, uninfected macrophages, suggesting an important role for uninfected macrophages in the early aggregative response. Reported is the first in vitro JD granuloma model capturing Map and macrophage viability, size distribution of resulting clusters, motility of monocyte-derived macrophages, and cytokine response during clustering, allowing quantitative analysis of multiple parameters of the Map-specific granulomatous response.


2006 ◽  
Vol 55 (7) ◽  
pp. 923-929 ◽  
Author(s):  
Austen Y. Chen ◽  
Scott R. Fry ◽  
Judy Forbes-Faulkner ◽  
Grant Daggard ◽  
T. K. S. Mukkur

The immunogenicity of P97 adhesin repeat region R1 (P97R1) of Mycoplasma hyopneumoniae, an important pathogenesis-associated region of P97, was evaluated in mice as a mucosal vaccine. Mice were immunized orally with attenuated Salmonella typhimurium aroA strain CS332 harbouring a eukaryotic or prokaryotic expression vector encoding P97R1. Local and systemic immune responses were analysed by ELISA on mouse sera, lung washes and splenocyte supernatants following splenocyte stimulation with specific antigens in vitro. Although no P97R1-specific antibody responses were detected in serum and lung washes, significant gamma interferon was produced by P97R1-stimulated splenocytes from mice immunized orally with S. typhimurium aroA harbouring either expression system, indicating induction of a cell-mediated immune response. These results suggested that live bacterial vectors carrying DNA vaccines or expressing heterologous antigens preferentially induce a Th1 response. Surprisingly, however, mice immunized with the vaccine carrier S. typhimurium aroA CS332 induced serum IgG, but not mucosal IgA, against P97R1 or S. typhimurium aroA CS332 whole-cell lysate, emphasizing the importance of assessing the suitability of attenuated S. typhimurium antigen-carrier delivery vectors in the mouse model prior to their evaluation as potential vaccines in the target species, which in this instance was pigs.


1993 ◽  
Vol 178 (2) ◽  
pp. 749-754 ◽  
Author(s):  
N McCartney-Francis ◽  
J B Allen ◽  
D E Mizel ◽  
J E Albina ◽  
Q W Xie ◽  
...  

Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.


2005 ◽  
Vol 33 (Web Server) ◽  
pp. W168-W171 ◽  
Author(s):  
U. Kulkarni-Kale ◽  
S. Bhosle ◽  
A. S. Kolaskar

2020 ◽  
Vol 222 (12) ◽  
pp. 1965-1973 ◽  
Author(s):  
Edward P Gniffke ◽  
Whitney E Harrington ◽  
Nicholas Dambrauskas ◽  
Yonghou Jiang ◽  
Olesya Trakhimets ◽  
...  

Abstract We present a microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to angiotensin-converting enzyme 2. Plasma from 22 patients who had recovered from mild coronavirus disease 2019 (COVID-19) and expressed anti–spike protein trimer immunoglobulin G inhibited angiotensin-converting enzyme 2–spike protein binding to a greater degree than controls. The degree of inhibition was correlated with anti–spike protein immunoglobulin G levels, neutralizing titers in a pseudotyped lentiviral assay, and the presence of fever during illness. This inhibition assay may be broadly useful to quantify the functional antibody response of patients recovered from COVID-19 or vaccine recipients in a cell-free assay system.


2018 ◽  
Vol 70 (2) ◽  
pp. 375-381 ◽  
Author(s):  
T.B. Roos ◽  
L.F.C. Avila ◽  
R.T. Sturbelle ◽  
F.L.L. Leite ◽  
G. Fischer ◽  
...  

ABSTRACT There have been significant efforts towards the development of more efficient vaccines for animal health. A strategy that may be used to improve vaccine efficacy is the use of probiotics to enhance the immune response of the host, leading to increased immunogenicity of antigen preparations. Bovine herpesvirus 5 (BoHV-5) is an example of an important animal pathogen for which vaccines have provided only limited protection. In this study, we examined the use of the probiotic Saccharomyces boulardii (Sb) as a potential adjuvant to improve vaccine efficiency. We found that the supplemented animals exhibited an enhanced systemic IgG antibody response toward a Th1 response in favor of IgG2a and increased mRNA expression levels of the cytokines IFN-y, IL-12, IL-17 and IL-10 in the spleen. These results suggest that Sb supplementation may provide a promising means for improving the efficiency of vaccines, particularly those that rely on a cell-mediated immune response.


2009 ◽  
Vol 1 ◽  
pp. OED.S2858 ◽  
Author(s):  
Robert E. Cone ◽  
Roshan Pais

The “immune privilege” that inhibits immune defense mechanisms that could lead to damage to sensitive ocular tissue is based on the expression of immunosuppressive factors on ocular tissue and in ocular fluids. In addition to this environmental protection, the injection of antigen into the anterior chamber or infection in the anterior chamber induces a systemic suppression of potentially damaging cell-mediated and humoral responses to the antigen. Here we discuss evidence that suggests that Anterior Chamber-Associated Immune Deviation (ACAID)a is initiated by an ocular response to moderate inflammation that leads to a systemic immunoregulatory response. Injection into the anterior chamber induces a rise in TNF-α and MCP-1 in aqueous humor and an infiltration of circulating F4/80+ monocytes that home to the iris. The induction of ACAID is dependent on this infiltration of circulating monocytes that eventually emigrate to the thymus and spleen where they induce regulatory T cells that inhibit the inductive or effector phases of a cell-mediated immune response. ACAID therefore protects the eye from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection.


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