scholarly journals Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

2020 ◽  
Vol 10 ◽  
Author(s):  
Marie-Noëlle Mévélec ◽  
Zineb Lakhrif ◽  
Isabelle Dimier-Poisson
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Vaccine Development ◽  
Host Immune Response ◽  
Oral Route ◽  
Effective Vaccine ◽  
Naked Dna ◽  
Protection Mechanisms ◽  
Immunogenic Proteins ◽  
Cellular Immune

Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of T. gondii tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite T. gondii vaccine candidates. Reflections on the development of an anti-Toxoplasma vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different T. gondii strains. Effective Toxoplasma vaccines depend on our understanding of the (1) protective host immune response during T. gondii invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.

scholarly journals SARS-CoV-2: From Structure to Pathology, Host Immune Response and Therapeutic Management

2020 ◽  
Vol 8 (10) ◽  
pp. 1468
Author(s):  
Grigore Mihaescu ◽  
Mariana Carmen Chifiriuc ◽  
Ciprian Iliescu ◽  
Corneliu Ovidiu Vrancianu ◽  
Lia-Mara Ditu ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Vaccine Development ◽  
Host Immune Response ◽  
Physical Factors ◽  
Respiratory Pathogens ◽  
Inflammatory Conditions ◽  
Multiplication Cycle ◽  
Wide Range

Coronaviruses are large, enveloped viruses with a single-stranded RNA genome, infecting both humans and a wide range of wild and domestic animals. SARS-CoV-2, the agent of the COVID-19 pandemic, has 80% sequence homology with SARS-CoV-1 and 96–98% homology with coronaviruses isolated from bats. The spread of infection is favored by prolonged exposure to high densities of aerosols indoors. Current studies have shown that SARS-CoV-2 is much more stable than other coronaviruses and viral respiratory pathogens. The severe forms of infection are associated with several risk factors, including advanced age, metabolic syndrome, diabetes, obesity, chronic inflammatory or autoimmune disease, and other preexisting infectious diseases, all having in common the pre-existence of a pro-inflammatory condition. Consequently, it is essential to understand the relationship between the inflammatory process and the specific immune response in SARS-CoV-2 infection. In this review, we present a general characterization of the SARS-CoV-2 virus (origin, sensitivity to chemical and physical factors, multiplication cycle, genetic variability), the molecular mechanisms of COVID-19 pathology, the host immune response and discuss how the inflammatory conditions associated with different diseases could increase the risk of COVID-19. Last, but not least, we briefly review the SARS-CoV-2 diagnostics, pharmacology, and future approaches toward vaccine development.

Strategies for search of pharmacological drugs against SARS-CoV-2 on the base of studying the structural-genetic features of coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2

2020 ◽  
Vol 18 (4) ◽  
pp. 269-296
Author(s):  
Vladimir I. Vashchenko ◽  
Vladimir N. Vilyaninov ◽  
Petr D. Shabanov
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Vaccine Development ◽  
Inflammatory Responses ◽  
Host Immune Response ◽  
Medication Cost ◽  
Atypical Pneumonia ◽  
Therapeutic Approaches ◽  
Mathematical Methods ◽  
Coronavirus Infection

A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. Also the basic molecular mechanisms of an atypical pneumonia and molecular targets SARS-CoV-2 that allows to allocate 8 basic directions of search of pharmacological agents for struggle with SARS-CoV-2 are discussed. Mathematical methods of search of perspective preparations for struggle with COVID-19 are in detail discussed. The pathophysiological mechanisms of an infection inducing a lymphopenia or cytokine storm that allows to allocate a special direction of search of pharmacological preparations for struggle against new coronaviruse SARS-CoV-2 are discussed.

scholarly journals Quantitative measurement of activity of JAK-STAT signaling pathways in blood samples and immune cells to predict innate and adaptive cellular immune response to viral infection and accelerate vaccine development

2020 ◽  
Author(s):  
Wilbert Bouwman ◽  
Wim Verhaegh ◽  
Laurent Holtzer ◽  
Anja van de Stolpe
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Signaling Pathways ◽  
Cellular Immune Response ◽  
Vaccine Development ◽  
Host Immune Response ◽  
Blood Samples ◽  
Pathway Activity ◽  
Adaptive Immune ◽  
Cellular Immune

AbstractThe host immune response determines the clinical course of a viral infection, for example in case of COVID-19 infection. The effectiveness of vaccination also depends on the induced immune response. Currently there is no method to measure the cellular immune response in blood samples. The functional activity of cells of innate and adaptive immune system is determined by coordinated activity of signaling pathways, especially the JAK-STAT pathways. Using a previously described approach we developed mRNA-based tests to measure activity of these signaling pathways, and show that they can be used to measure in a quantitative manner the cellular innate and adaptive immune response to a viral infection or vaccine in whole blood, PBMC, and specific immune cell type samples. Pathway activity level and range in healthy individuals was established, enabling interpretation of a pathway activity score on a patient sample without the need for a reference sample. Evidence is presented that the pathway activity analysis may also be useful for in vitro vaccine development and assessment of vaccine immunogenicity. Other envisioned applications lie in development of immunomodulatory drugs and drug response prediction and monitoring. Tests are expected to be of value in the COVID-19 crisis. In addition to the described Affymetrix microarray-based pathway tests for measuring host immune response, qPCR-based versions are in development; the latter can in principle be performed within three hours in routine hospital labs.

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 Göttingen Minipigs as a Model to Evaluate Longevity, Functionality, and Memory of Immune Response Induced by Pertussis Vaccines

2021 ◽  
Vol 12 ◽  
Author(s):  
Céline Vaure ◽  
Véronique Grégoire-Barou ◽  
Virginie Courtois ◽  
Emilie Chautard ◽  
Cyril Dégletagne ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Vaccine Development ◽  
Vaccination Schedule ◽  
Memory B Cells ◽  
Immune Memory ◽  
Preclinical Model ◽  
Göttingen Minipig ◽  
Cellular Immune

Evaluation of the short-term and long-term immunological responses in a preclinical model that simulates the targeted age population with a relevant vaccination schedule is essential for human vaccine development. A Göttingen minipig model was assessed, using pertussis vaccines, to demonstrate that vaccine antigen-specific humoral and cellular responses, including IgG titers, functional antibodies, Th polarization and memory B cells can be assessed in a longitudinal study. A vaccination schedule of priming with a whole cell (DTwP) or an acellular (DTaP) pertussis vaccine was applied in neonatal and infant minipigs followed by boosting with a Tdap acellular vaccine. Single cell RNAsequencing was used to explore the long-term maintenance of immune memory cells and their functionality for the first time in this animal model. DTaP but not DTwP vaccination induced pertussis toxin (PT) neutralizing antibodies. The cellular immune response was also characterized by a distinct Th polarization, with a Th-2-biased response for DTaP and a Th-1/Th-17-biased response for DTwP. No difference in the maintenance of pertussis-specific memory B cells was observed in DTaP- or DTwP-primed animals 6 months post Tdap boost. However, an increase in pertussis-specific T cells was still observed in DTaP primed minipigs, together with up-regulation of genes involved in antigen presentation and interferon pathways. Overall, the minipig model reproduced the humoral and cellular immune responses induced in humans by DTwP vs. DTaP priming, followed by Tdap boosting. Our data suggest that the Göttingen minipig is an attractive preclinical model to predict the long-term immunogenicity of human vaccines against Bordetella pertussis and potentially also vaccines against other pathogens.

scholarly journals Genes that control vaccinia virus immunogenicity

Acta Naturae ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Sergey Shchelkunov ◽  
G. A. Shchelkunova
Keyword(s):  
Immune Response ◽  
Side Effects ◽  
Genetic Engineering ◽  
Vaccinia Virus ◽  
Cellular Immune Response ◽  
Human Population ◽  
Effective Vaccine ◽  
Global Eradication ◽  
Cellular Immune ◽  
High Immunogenicity

The live smallpox vaccine was a historical first and highly effective vaccine. However, along with high immunogenicity, the vaccinia virus (VACV) caused serious side effects in vaccinees, sometimes with lethal outcomes. Therefore, after global eradication of smallpox, VACV vaccination was stopped. For this reason, most of the human population worldwide lacks specific immunity against not only smallpox, but also other zoonotic orthopoxviruses. Outbreaks of diseases caused by these viruses have increasingly occurred in humans on different continents. However, use of the classical live VACV vaccine for prevention against these diseases is unacceptable because of potential serious side effects, especially in individuals with suppressed immunity or immunodeficiency (e.g., HIV-infected patients). Therefore, highly attenuated VACV variants that preserve their immunogenicity are needed. This review discusses current ideas about the development of a humoral and cellular immune response to orthopoxvirus infection/vaccination and describes genetic engineering approaches that could be utilized to generate safe and highly immunogenic live VACV vaccines.

scholarly journals Induction of Cellular Immune Response by DNA Vaccine CoexpressingE. acervulina3-1E Gene and Mature CHIl-15 Gene

2012 ◽  
Vol 2012 ◽  
pp. 1-7
Author(s):  
Dexing Ma ◽  
Chunli Ma ◽  
Mingyang Gao ◽  
Guangxing Li ◽  
Ze Niu ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Vaccine ◽  
Cellular Immune Response ◽  
Lymphocyte Proliferation ◽  
Vaccine Development ◽  
Flow Cytometric Analysis ◽  
Potential Candidate ◽  
Spleen Lymphocyte ◽  
Cellular Immune ◽  
And Control

We previously reported that the chimeric DNA vaccine pcDNA-3-1E-linker-mChIL-15, fused through linkingEimeria acervulina3-1E encoding gene and mature chicken IL-15 (mChIL-15) gene with four flexible amino acid SPGS, could significantly offer protection against homologous challenge. In the present study, the induction of cellular immune response induced by the chimeric DNA vaccine pcDNA-3-1E-linker-mChIL-15 was investigated. Spleen lymphocyte subpopulations were characterized by flow cytometric analysis. The spleen lymphocyte proliferation assays were measured by 3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide (MTT) method. The mRNA profiles of ChIL-2 and ChIFN-γ in spleen were characterized by means of real-time PCR. Chickens immunized with pcDNA-3-1E-linker-mChIL-15 exhibited significant upregulated level of ChIL-2 and ChIFN-γ transcripts in spleen following two immunizations compared with chickens in other groups (P<0.01). In comparison with pcDNA3.1-immunized and control groups, lymphocyte proliferation, percentage of CD8α+cell, and levels of ChIL-2 and ChIFN-γ transcripts in the group immunized with pcDNA-3-1E-linker-mChIL-15 were significantly increased on day 6 following challenge (P<0.05,P<0.01, andP<0.01, resp.). Our data suggested that the fusion antigen 3-1E-linker-mChIL-15 could be a potential candidate forE. acervulinavaccine development.

scholarly journals Immune Response to COVID-19: Can We Benefit from the SARS-CoV and MERS-CoV Pandemic Experience?

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 739
Author(s):  
Emilia Sinderewicz ◽  
Wioleta Czelejewska ◽  
Katarzyna Jezierska-Wozniak ◽  
Joanna Staszkiewicz-Chodor ◽  
Wojciech Maksymowicz
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Vaccine Development ◽  
T Cell Response ◽  
High Fatality Rate ◽  
Scientific World ◽  
Specific Antibody Production ◽  
Potential Vaccine ◽  
Cellular Immune

The global range and high fatality rate of the newest human coronavirus (HCoV) pandemic has made SARS-CoV-2 the focus of the scientific world. Next-generation sequencing of the viral genome and a phylogenetic analysis have shown the high homology of SARS-CoV-2 to other HCoVs that have led to local epidemics in the past. The experience acquired in SARS and MERS epidemics may prove useful in understanding the SARS-CoV-2 pathomechanism and lead to effective treatment and potential vaccine development. This study summarizes the immune response to SARS-CoV, MERS-CoV, and SARS-CoV-2 and focuses on T cell response, humoral immunity, and complement system activation in different stages of HCoVs infections. The study also presents the quantity and frequency of T cell responses, particularly CD4+ and CD8+; the profile of cytokine production and secretion; and its relation to T cell type, disease severity, and utility in prognostics of the course of SARS, MERS, and COVID-19 outbreaks. The role of interferons in the therapy of these infections is also discussed. Moreover, the kinetics of specific antibody production, the correlation between humoral and cellular immune response and the immunogenicity of the structural HCoVs proteins and their utility in the development of a vaccine against SARS, MERS, and COVID-19 has been updated.

scholarly journals Single-Dose Mucosal Immunization with Biodegradable Microparticles Containing a Schistosoma mansoniAntigen

1999 ◽  
Vol 67 (5) ◽  
pp. 2643-2648 ◽  
Author(s):  
Benoît Baras ◽  
Marie-Ange Benoit ◽  
Loïc Dupré ◽  
Odile Poulain-Godefroy ◽  
Anne-Marie Schacht ◽  
...  
Keyword(s):  
Immune Response ◽  
Enzymatic Activity ◽  
Vaccine Development ◽  
Serum Antibody ◽  
Oral Route ◽  
Single Administration ◽  
Mucosal Immunization ◽  
Specific Serum ◽  
Specific Antisera ◽  
Biodegradable Microparticles

ABSTRACT The purpose of this work was to assess the immunogenicity of a single nasal or oral administration of recombinant 28-kDa glutathioneS-transferase of Schistosoma mansoni (rSm28GST) entrapped by poly(lactide-co-glycolide) (PLG)- or polycaprolactone (PCL)-biodegradable microparticles. Whatever the polymer and the route of administration used, the equivalent of 100 μg of entrapped rSm28GST induced a long-lasting and stable antigen-specific serum antibody response, with a peak at 9 to 10 weeks following immunization. Isotype profiles were comparable, with immunoglobulin G1 being the predominant isotype produced. The abilities of specific antisera to neutralize the rSm28GST enzymatic activity have been used as criteria of immune response quality. Pooled 10-week sera from mice receiving PLG microparticles by the nasal or oral route neutralized the rSm28GST enzymatic activity, whereas sera of mice receiving either PCL microparticles, free rSm28GST, or empty microparticles inefficiently neutralized this enzymatic activity. Finally, this study shows that a single administration of these microparticles could provide distinct and timely release pulses of microencapsulated antigen, which might greatly facilitate future vaccine development.

scholarly journals Codon Usage and Adenovirus Fitness: Implications for Vaccine Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Judit Giménez-Roig ◽  
Estela Núñez-Manchón ◽  
Ramon Alemany ◽  
Eneko Villanueva ◽  
Cristina Fillat
Keyword(s):  
Immune Response ◽  
Codon Usage ◽  
Viral Vectors ◽  
Vaccine Development ◽  
Health Hazard ◽  
Recombinant Vaccines ◽  
Viral Epitope ◽  
Naturally Occurring ◽  
Cellular Immune ◽  
Viral Attenuation

Vaccination is the most effective method to date to prevent viral diseases. It intends to mimic a naturally occurring infection while avoiding the disease, exposing our bodies to viral antigens to trigger an immune response that will protect us from future infections. Among different strategies for vaccine development, recombinant vaccines are one of the most efficient ones. Recombinant vaccines use safe viral vectors as vehicles and incorporate a transgenic antigen of the pathogen against which we intend to generate an immune response. These vaccines can be based on replication-deficient viruses or replication-competent viruses. While the most effective strategy involves replication-competent viruses, they must be attenuated to prevent any health hazard while guaranteeing a strong humoral and cellular immune response. Several attenuation strategies for adenoviral-based vaccine development have been contemplated over time. In this paper, we will review them and discuss novel approaches based on the principle that protein synthesis from individual genes can be modulated by codon usage bias manipulation. We will summarize vaccine approaches that consider recoding of viral proteins to produce adenoviral attenuation and recoding of the transgene antigens for both viral attenuation and efficient viral epitope expression.

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