scholarly journals Development of an Oral Salmonella-Based Vaccine Platform against SARS-CoV-2

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 67
Author(s):  
Wonsuck Yoon ◽  
Yongsung Park ◽  
Seunghyun Kim ◽  
Iel Soo Bang
Keyword(s):  
Large Scale ◽  
Vaccine Development ◽  
Oral Vaccine ◽  
Oral Bacteria ◽  
Expression Vectors ◽  
Effective Vaccine ◽  
Vaccine Platform ◽  
In Vivo Experiments

Effective vaccine development for global outbreaks, such as the coronavirus disease 2019 (COVID-19), has been successful in the short run. However, the currently available vaccines have been associated with a higher frequency of adverse effects compared with other general vaccines. In this study, the possibility of an oral bacteria-based vaccine that can be safely used as a platform for large-scale, long-term immunization was evaluated. A well-known Salmonella strain that was previously considered as a vaccine delivery candidate was used. Recombinant Salmonella cells expressing engineered viral proteins related with COVID-19 pathogenesis were engineered, and the formulation of the oral vaccine candidate strain was evaluated by in vitro and in vivo experiments. First, engineered S proteins were synthesized and cloned into expression vectors, which were than transformed into Salmonella cells. In addition, when orally administrated to mice, the vaccine promoted antigen-specific antibody production and cellular immunity was induced with no significant toxicity effects. These results suggest that Salmonella strains may represent a valuable platform for the development of an oral vaccine for COVID-19 as an alternative to tackle the outbreak of various mutated coronavirus strains and new infectious diseases in the future.

scholarly journals A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1408
Author(s):  
Qiao Li ◽  
Zhihua Liu ◽  
Yi Liu ◽  
Chen Liang ◽  
Jiayi Shu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Inbred Mouse ◽  
Effective Vaccine ◽  
Mouse Strains ◽  
Cellular Immune Responses ◽  
Recombinant Hbsag ◽  
Cellular Immune

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.

scholarly journals Resolution ofStaphylococcus aureusBiofilm Infection Using Vaccination and Antibiotic Treatment

2011 ◽  
Vol 79 (4) ◽  
pp. 1797-1803 ◽  
Author(s):  
Rebecca A. Brady ◽  
Graeme A. O'May ◽  
Jeff G. Leid ◽  
Megan L. Prior ◽  
J. William Costerton ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Vaccine Development ◽  
Hypothetical Protein ◽  
Quadrivalent Vaccine ◽  
Effective Vaccine ◽  
Vast Number ◽  
Protective Antigens ◽  
Biofilm Model

ABSTRACTStaphylococcus aureusinfections, particularly those from methicillin-resistant strains (i.e., MRSA), are reaching epidemic proportions, with no effective vaccine available. The vast number and transient expression of virulence factors in the infectious course of this pathogen have made the discovery of protective antigens particularly difficult. In addition, the divergent planktonic and biofilm modes of growth with their accompanying proteomic changes also demonstrate significant hindrances to vaccine development. In this study, a multicomponent vaccine was evaluated for its ability to clear a staphylococcal biofilm infection. Antigens (glucosaminidase, an ABC transporter lipoprotein, a conserved hypothetical protein, and a conserved lipoprotein) were chosen since they were found in previous studies to have upregulated and sustained expression in a biofilm, bothin vitroandin vivo. Antibodies against these antigens were first used in microscopy studies to localize their expression inin vitrobiofilms. Each of the four antigens showed heterogeneous production in various locations within the complex biofilm community in the biofilm. Based upon these studies, the four antigens were delivered simultaneously as a quadrivalent vaccine in order to compensate for this varied production. In addition, antibiotic treatment was also administered to clear the remaining nonattached planktonic cells since the vaccine antigens may have been biofilm specific. The results demonstrated that when vaccination was coupled with vancomycin treatment in a biofilm model of chronic osteomyelitis in rabbits, clinical and radiographic signs of infection significantly reduced by 67 and 82%, respectively, compared to infected animals that were either treated with vancomycin or left untreated. In contrast, vaccination alone resulted in a modest, and nonsignificant, decrease in clinical (34% reduction) and radiographic signs (9% reduction) of infection, compared to nonvaccinated animal groups untreated or treated with vancomycin. Lastly, MRSA biofilm infections were significantly cleared in 87.5% of vaccinated and antibiotic-treated animals, while antibiotics or vaccine alone could not significantly clear infection compared to controls (55.6, 22.2, and 33.3% clearance rates, respectively). This approach to vaccine development may lead to the generation of vaccines against other pathogenic biofilm bacteria.

Deep Learning in Drug Target Interaction Prediction: Current and Future Perspective

2020 ◽  
Vol 27 ◽  
Author(s):  
Karim Abbasi ◽  
Parvin Razzaghi ◽  
Antti Poso ◽  
Saber Ghanbari-Ara ◽  
Ali Masoudi-Nejad
Keyword(s):  
Deep Learning ◽  
Drug Target ◽  
Large Scale ◽  
Future Perspective ◽  
Multiple Perspectives ◽  
Comprehensive Overview ◽  
In Vivo Experiments ◽  
Drug Compound

Drug-target Interactions (DTIs) prediction plays a central role in drug discovery. Computational methods in DTIs prediction have gotten more attention because carrying out in vitro and in vivo experiments on a large scale is costly and time-consuming. Machine learning methods, especially deep learning, are widely applied to DTIs prediction. In this study, the main goal is to provide a comprehensive overview of deep learning-based DTIs prediction approaches. Here, we investigate the existing approaches from multiple perspectives. We explore these approaches to find out which deep network architectures are utilized to extract features from drug compound and protein sequences. Also, the advantages and limitations of each architecture are analyzed and compared. Moreover, we explore the process of how to combine descriptors for drug and protein features. Likewise, a list of datasets that are commonly used in DTIs prediction is investigated. Finally, current challenges are discussed and a short future outlook of deep learning in DTI prediction is given.

scholarly journals In Vitro and In Vivo Characterization of MicroRNA-Targeted Alphavirus Replicon and Helper RNAs

2010 ◽  
Vol 84 (15) ◽  
pp. 7713-7725 ◽  
Author(s):  
Kurt I. Kamrud ◽  
V. McNeil Coffield ◽  
Gary Owens ◽  
Christin Goodman ◽  
Kim Alterson ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Rna Replication ◽  
Structural Proteins ◽  
Expression Vectors ◽  
Cellular Mirnas ◽  
Rna Regulation ◽  
Oncolytic Adenoviruses ◽  
Vector Systems

ABSTRACT Alphavirus-based replicon vector systems (family Togaviridae) have been developed as expression vectors with demonstrated potential in vaccine development against both infectious diseases and cancer. The single-cycle nature of virus-like replicon particles (VRP), generated by supplying the structural proteins from separate replicable helper RNAs, is an attractive safety component of these systems. MicroRNAs (miRNAs) have emerged as important cellular RNA regulation elements. Recently, miRNAs have been employed as a mechanism to attenuate or restrict cellular tropism of replication-competent viruses, such as oncolytic adenoviruses, vesicular stomatitis virus, and picornaviruses as well as nonreplicating lentiviral and adenoviral vectors. Here, we describe the incorporation of miRNA-specific target sequences into replicable alphavirus helper RNAs that are used in trans to provide the structural proteins required for VRP production. VRP were found to be efficiently produced using miRNA-targeted helper RNAs if miRNA-specific inhibitors were introduced into cells during VRP production. In the absence of such inhibitors, cellular miRNAs were capable of downregulating helper RNA replication in vitro. When miRNA targets were incorporated into a replicon RNA, cellular miRNAs were capable of downregulating replicon RNA replication upon delivery of VRP into animals, demonstrating activity in vivo. These data provide the first example of miRNA-specific repression of alphavirus replicon and helper RNA replication and demonstrate the feasibility of miRNA targeting of expression vector helper functions that are provided in trans.

scholarly journals Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine

2021 ◽  
Vol 11 ◽  
Author(s):  
Magda Melissa Flórez ◽  
Rocío Rodríguez ◽  
José Antonio Cabrera ◽  
Sara M. Robledo ◽  
Gabriela Delgado
Keyword(s):  
Immune Response ◽  
In Silico ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Epitope Prediction ◽  
Effective Vaccine ◽  
Peripheral Blood Mononuclear

Vaccines are one of the most effective strategies to fight infectious diseases. Reverse vaccinology strategies provide tools to perform in silico screening and a rational selection of potential candidates on a large scale before reaching in vitro and in vivo evaluations. Leishmania infection in humans produces clinical symptoms in some individuals, while another part of the population is naturally resistant (asymptomatic course) to the disease, and therefore their immune response controls parasite replication. By the identification of epitopes directly in humans, especially in those resistant to the disease, the probabilities of designing an effective vaccine are higher. The aim of this work was the identification of Leishmania epitopes in resistant humans. To achieve that, 11 peptide sequences (from Leishmania antigenic proteins) were selected using epitope prediction tools, and then, peripheral blood mononuclear cells (PBMCs) were isolated from human volunteers who were previously divided into four clinical groups: susceptible, resistant, exposed and not exposed to the parasite. The induction of inflammatory cytokines and lymphoproliferation was assessed using monocyte-derived dendritic cells (moDCs) as antigen-presenting cells (APCs). The response was evaluated after exposing volunteers’ cells to each peptide. As a result, we learned that STI41 and STI46 peptides induced IL-8 and IL-12 in moDCs and lymphoproliferation and low levels of IL-10 in lymphocytes differentially in resistant volunteers, similar behavior to that observed in those individuals to L. panamensis lysate antigens. We conclude that, in silico analysis allowed for the identification of natural Leishmania epitopes in humans, and also STI41 and STI46 peptides could be epitopes that lead to a cellular immune response directed at parasite control.

scholarly journals High immune efficacy against different avian influenza H5N1 viruses due to oral administration of a Saccharomyces cerevisiae-based vaccine in chickens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Han Lei ◽  
Xin Lu ◽  
Shuangqin Li ◽  
Yi Ren
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Avian Influenza ◽  
Oral Administration ◽  
Large Scale ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Oral Vaccine ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Live Virus

AbstractA safe and effective vaccine is the best way to control large-scale highly pathogenic avian influenza virus (HPAI) A (H5N1) outbreaks. Saccharomyces cerevisiae (S. cerevisiae) is an ideal mucosal delivery vector for vaccine development, and we have previously shown that conventional administration of a S. cerevisiae-based vaccine (EBY100/pYD1-HA) via injection led to protection against the homologous H5N1 virus in a mouse model. Because the diameter of S. cerevisiae is approximately 10 μm, which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring protection in poultry. We extended our work by evaluating the immunogenicity and protective efficacy of oral vaccination with EBY100/pYD1-HA in the chicken model. Oral immunization with EBY100/pYD1-HA could induce robust serum IgG, mucosal IgA and cellular immune responses. Importantly, EBY100/pYD1-HA provided protection against challenges with a homologous and a heterologous H5N1 viruses. These findings suggest that EBY100/pYD1-HA, a promising H5N1 oral vaccine candidate, can avoid potential reassortment of other avian influenza viruses in oral administration of live virus vaccines and overcome the limitations of conventional injection routes. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.

scholarly journals Anticytomegalovirus Peptides Point to New Insights for CMV Entry Mechanisms and the Limitations ofIn VitroScreenings

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Joseph W. Jackson ◽  
Trevor J. Hancock ◽  
Pranay Dogra ◽  
Ravi Patel ◽  
Ravit Arav-Boger ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Vaccine Development ◽  
Murine Cytomegalovirus ◽  
Effective Vaccine ◽  
Antiviral Peptides ◽  
Highly Effective ◽  
Binding Peptides ◽  
Cell Spread

ABSTRACTHuman cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that can cause severe disease followingin uteroexposure, during primary infection, or latent virus reactivation in immunocompromised populations. These complications lead to a 1- to 2-billion-dollar economic burden, making vaccine development and/or alternative treatments a high priority. Current treatments for HCMV include nucleoside analogues such as ganciclovir (GCV), foscarnet, and cidofovir. Recently, letermovir, a terminase complex inhibitor, was approved for prophylaxis after stem cell transplantation. These treatments have unwanted side effects, and HCMV is becoming resistant to them. Therefore, we sought to develop an alternative treatment that targets a different stage in viral infection. Currently, small antiviral peptides are being investigated as anti-influenza and anti-HIV treatments. We have developed heparan sulfate-binding peptides as tools for preventing CMV infections. These peptides are highly effective at stopping infection of fibroblasts within vitro-derived HCMV and murine cytomegalovirus (MCMV). However, they do not prevent MCMV infectionin vivo. Interestingly, these peptides inhibit infectivity ofin vivo-derived CMVs, albeit not as well as tissue culture-grown CMVs. We further demonstrate that this class of heparan sulfate-binding peptides is incapable of inhibiting MCMV cell-to-cell spread, which is independent of heparan sulfate usage. These data indicate that inhibition of CMV infection can be achieved using synthetic polybasic peptides, but cell-to-cell spread andin vivo-grown CMVs require further investigation to design appropriate anti-CMV peptides.IMPORTANCEIn the absence of an effective vaccine to prevent HCMV infections, alternative interventions must be developed. Prevention of viral entry into susceptible cells is an attractive alternative strategy. Here we report that heparan sulfate-binding peptides effectively inhibit entry into fibroblasts ofin vitro-derived CMVs and partially inhibitin vivo-derived CMVs. This includes the inhibition of urine-derived HCMV (uCMV), which is highly resistant to antibody neutralization. While these antiviral peptides are highly effective at inhibiting cell-free virus, they do not inhibit MCMV cell-to-cell spread. This underscores the need to understand the mechanism of cell-to-cell spread and differences betweenin vivo-derived versusin vitro-derived CMV entry to effectively prevent CMV’s spread.

scholarly journals Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 131 ◽  
Author(s):  
Cristina Poveda ◽  
Amadeo B. Biter ◽  
Maria Elena Bottazzi ◽  
Ulrich Strych
Keyword(s):  
Messenger Rna ◽  
Large Scale ◽  
Vaccine Development ◽  
Regulatory Compliance ◽  
Rapid Screening ◽  
Vaccine Antigen ◽  
Product Characteristics ◽  
Early Assessment

The preferred product characteristics (for chemistry, control, and manufacture), in addition to safety and efficacy, are quintessential requirements for any successful therapeutic. Messenger RNA vaccines constitute a relatively new alternative to traditional vaccine development platforms, and thus there is less clarity regarding the criteria needed to ensure regulatory compliance and acceptance. Generally, to identify the ideal product characteristics, a series of assays needs to be developed, qualified and ultimately validated to determine the integrity, purity, stability, and reproducibility of a vaccine target. Here, using the available literature, we provide a summary of the array of biophysical and biochemical assays currently used in the field to characterize mRNA vaccine antigen candidates. Moreover, we review various in vitro functional cell-based assays that have been employed to facilitate the early assessment of the biological activity of these molecules, including the predictive immune response triggered in the host cell. Messenger RNA vaccines can be produced rapidly and at large scale, and thus will particularly benefit from well-defined and well-characterized assays ultimately to be used for in-process, release and stability-indications, which will allow equally rapid screening of immunogenicity, efficacy, and safety without the need to conduct often lengthy and costly in vivo experiments.

scholarly journals Synthetic Peptides Elicit Strong Cellular Immunity in Visceral Leishmaniasis Natural Reservoir and Contribute to Long-Lasting Polyfunctional T-Cells in BALB/c Mice

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 162 ◽  
Author(s):  
Rory Cristiane Fortes De Brito ◽  
Jamille Mirelle de Oliveira Cardoso ◽  
Levi Eduardo Soares Reis ◽  
Fernando Augusto Siqueira Mathias ◽  
Rodrigo Dian de Oliveira Aguiar-Soares ◽  
...  
Keyword(s):  
T Cells ◽  
Visceral Leishmaniasis ◽  
In Silico ◽  
Vaccine Development ◽  
Subcellular Location ◽  
Effector Memory ◽  
Effective Vaccine ◽  
Polyfunctional T Cells

Reverse vaccinology or immunoinformatics is a computational methodology which integrates data from in silico epitope prediction, associated to other important information as, for example, the predicted subcellular location of the proteins used in the design of the context of vaccine development. This approach has the potential to search for new targets for vaccine development in the predicted proteome of pathogenic organisms. To date, there is no effective vaccine employed in vaccination campaigns against visceral leishmaniasis (VL). For the first time, herein, an in silico, in vitro, and in vivo peptide screening was performed, and immunogenic peptides were selected to constitute VL peptide-based vaccines. Firstly, the screening of in silico potential peptides using dogs naturally infected by L. infantum was conducted and the peptides with the best performance were selected. The mentioned peptides were used to compose Cockt-1 (cocktail 1) and Cockt-2 (cocktail 2) in combination with saponin as the adjuvant. Therefore, tests for immunogenicity, polyfunctional T-cells, and the ability to induce central and effector memory in T-lymphocytes capacity in reducing the parasite load on the spleen for Cockt-1 and Cockt-2 were performed. Among the vaccines under study, Cockt-1 showed the best results, eliciting CD4+ and CD8+ polyfunctional T-cells, with a reduction in spleen parasitism that correlates to the generation of T CD4+ central memory and T CD8+ effector memory cells. In this way, our findings corroborate the use of immunoinformatics as a tool for the development of future vaccines against VL.

scholarly journals A capsular polysaccharide-expressing live vaccine suppresses streptococcal toxic shock-like syndrome and provides sequence type-independent protection during Streptococcus suis infection

2018 ◽  
Author(s):  
Zhiwei Li ◽  
Peixi Chang ◽  
Jiali Xu ◽  
Chen Tan ◽  
Xiaohong Wang ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Streptococcus Suis ◽  
Sequence Type ◽  
Effective Vaccine ◽  
Toxic Shock ◽  
Proinflammatory Responses

AbstractStreptococcus suis (S. suis) is an encapsulated zoonotic pathogen, which is responsible for bacterial meningitis and streptococcal toxic shock-like syndrome (STSLS). Despite many attempts to develop an effective vaccine, none is currently available. Here, a capsular polysaccharide (CPS)-expressing attenuated mutant 2015033 was constructed by deleting five virulence-associated factors (sly, scpA, ssnA, fhb, and ssads) in an outbreak S. suis strain SC19. Genes mentioned above are associated with either innate immunity-evading or tissue barrier-invading. Deletion of these genes did not impact the growth ability and CPS generation of 2015033, and the mutant exhibited no hemolytic activity to erythrocytes and no cytotoxicity to different epithelial or endothelial cells. In addition, 2015033 was more easily eliminated by whole human blood in vitro and by mouse blood in vivo. In addition, 2015033 showed a diminished invasive ability in different mouse organs (brain, lung, and liver) and avirulent properties in mice associated with weak inflammation-inducing ability. Immunization with 2015033 triggered T cell-dependent immunity and this immunity suppressed STSLS during SC19 infection by inhibiting excessive proinflammatory responses. In addition, immunization with 2015033 successfully conferred sequence type (STs)-independent protection to mice during heterogeneous infections (ST1, ST7, and ST658). This study presents the feasibility of the strategy of multi-gene deletion for the development of promising live vaccines against invasive encapsulated pathogens.IMPORTANCES. suis is a traditional zoonotic agent causing human meningitis and STSLS, which is also a neglected emerging food-borne pathogen. Increasing antimicrobial resistance invokes reduction of preventative use of antibiotics in livestock creating an urgent need for effective vaccines. Given the expression of CPS is the basis for promising vaccines against encapsulated pathogens, and in order to find an effective and economical strategy for CPS-based vaccine development, multi-gene deletion was introduced into the design of a S. suis vaccine for the first time. From our results, CPS-expressing attenuated mutant 2015033 exhibited diminished evasive ability against the innate immune system and reduced invasive properties against different host barriers. To our knowledge, 2015033 is the first STSLS-suppressing S. suis vaccine to provide STs-independent protection during heterogeneous infections.

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