scholarly journals New Strategies for Prevention and Treatment of Insect Bite Hypersensitivity in Horses

2019 ◽  
Vol 8 (4) ◽  
pp. 303-312 ◽  
Author(s):  
Sigridur Jonsdottir ◽  
Iva Cvitas ◽  
Vilhjalmur Svansson ◽  
Antonia Fettelschloss-Gabriel ◽  
Sigurbjorg Torsteinsdottir ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Clinical Signs ◽  
Therapeutic Vaccines ◽  
Allergen Specific Immunotherapy ◽  
Virus Like Particle ◽  
Prevention And Treatment ◽  
Prophylactic Vaccination ◽  
Insect Bite Hypersensitivity ◽  
Icelandic Horses ◽  
New Strategies

Abstract Purpose of Review Treatment of equine insect bite hypersensitivity (IBH) needs to be improved. Allergen-specific immunotherapy (ASIT), the only curative treatment of allergy, currently has only a limited efficacy for treatment of IBH. This review highlights the latest findings in prophylactic and therapeutic strategies. Recent Findings Prophylactic vaccination against IBH using recombinant Culicoides allergen has been developed in unexposed Icelandic horses and is ready to be tested. Therapeutic virus-like particle (VLP)–based vaccines targeting equine interleukin- (IL-) 5 or IL-31 improved clinical signs of IBH by induction of anti-cytokine antibodies thus reducing eosinophil counts or allergic pruritus, respectively. Summary First studies for development of ASIT using pure r-Culicoides allergens have yielded promising results and need now to be tested in clinical studies for both prevention and treatment of IBH. Therapeutic vaccines inducing neutralizing antibodies against IL-5 or IL-31 will be valuable future treatments for reduction of clinical signs of IBH.

Modern molecular and biological aspects of endometriosis-associated infertility

GYNECOLOGY ◽  
2019 ◽  
Vol 21 (5) ◽  
pp. 12-15
Author(s):  
Anastasiia S Safronova ◽  
Mikhail Yu Vysokikh ◽  
Vladimir D Chuprynin ◽  
Natalia A Buralkina
Keyword(s):  
Signaling Pathways ◽  
Recurrence Rate ◽  
High Recurrence Rate ◽  
Modern Drug ◽  
Surgical Methods ◽  
Prevention And Treatment ◽  
Biological Aspects ◽  
Methods Of Treatment ◽  
New Strategies

There is currently no consensus on the etiopathogenetic nature of endometriosis. The causes of aggressive, progressive, infiltrative growth of endometrioid tissue also remain unclear. An important problem remains the high recurrence rate of endometriosis, despite the availability of modern drug and surgical methods of treatment. The study of the central signaling pathways and the search for new key molecules is of paramount importance for a better understanding of the pathogenesis of the disease, and is also an important step in the development of new strategies for the diagnosis, prevention and treatment of endometriosis.

scholarly journals HIV mRNA Vaccines—Progress and Future Paths

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 134
Author(s):  
Zekun Mu ◽  
Barton F. Haynes ◽  
Derek W. Cain
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Vaccination Strategy ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cytotoxic T Cell ◽  
Therapeutic Vaccines ◽  
Cell Responses ◽  
Broadly Neutralizing Antibody ◽  
Cytotoxic T Cell Responses

The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.

scholarly journals Recent advances in understanding and preventing human papillomavirus-related disease

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 269 ◽  
Author(s):  
Karin Hellner ◽  
Lucy Dorrell
Keyword(s):  
Antiviral Agents ◽  
Intraepithelial Neoplasia ◽  
Human Papillomaviruses ◽  
Surgical Approaches ◽  
Therapeutic Vaccines ◽  
Middle Income ◽  
Recent Advances ◽  
Resource Limited ◽  
Technological Advances ◽  
Prophylactic Vaccination

High-risk human papillomaviruses (hrHPV) are responsible for anogenital and oropharyngeal cancers, which together account for at least 5% of cancers worldwide. Industrialised nations have benefitted from highly effective screening for the prevention of cervical cancer in recent decades, yet this vital intervention remains inaccessible to millions of women in low- and middle-income countries (LMICs), who bear the greatest burden of HPV disease. While there is an urgent need to increase investment in basic health infrastructure and rollout of prophylactic vaccination, there are now unprecedented opportunities to exploit recent scientific and technological advances in screening and treatment of pre-invasive hrHPV lesions and to adapt them for delivery at scale in resource-limited settings. In addition, non-surgical approaches to the treatment of cervical intraepithelial neoplasia and other hrHPV lesions are showing encouraging results in clinical trials of therapeutic vaccines and antiviral agents. Finally, the use of next-generation sequencing to characterise the vaginal microbial environment is beginning to shed light on host factors that may influence the natural history of HPV infections. In this article, we focus on recent advances in these areas and discuss their potential for impact on HPV disease.

scholarly journals Strategies for Optimizing the Clinical Impact of Immunotherapeutic Agents Such as Sipuleucel-T in Prostate Cancer

2012 ◽  
Vol 10 (12) ◽  
pp. 1505-1512 ◽  
Author(s):  
Ravi A. Madan ◽  
Thomas Schwaab ◽  
James L. Gulley
Keyword(s):  
Prostate Cancer ◽  
Immune Responses ◽  
Standard Of Care ◽  
Clinical Impact ◽  
Castration Resistant Prostate Cancer ◽  
Therapeutic Vaccines ◽  
Therapeutic Cancer Vaccine ◽  
Castration Resistant ◽  
New Strategies

Sipuleucel-T is a therapeutic cancer vaccine that has shown improved survival in men with metastatic castration-resistant prostate cancer. As a first-in-class agent, it has been met with both fan-fare and controversy. A broad review of immune-based therapies may reveal the delayed clinical impact of sipuleucel-T to be a class effect. As new strategies of immune-based therapy are developed, their effects can be optimized through better understanding of how they affect disease differently from more standard therapeutics. Furthermore, combination therapy with agents that can either work synergistically with immune-activating therapies or deplete immune-regulating cells may result in more vigorous immune responses and improved clinical outcomes. In addition, therapeutic vaccines may be ideal candidates to safely combine with standard-of-care therapies because of their nonoverlapping toxicity profile. The ultimate role of immunotherapy may not be to supplant standard therapies, but rather to work in concert with them to maximize clinical benefit for patients.

scholarly journals Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection

2016 ◽  
Vol 12 (3) ◽  
pp. e1005520 ◽  
Author(s):  
Kshitij Wagh ◽  
Tanmoy Bhattacharya ◽  
Carolyn Williamson ◽  
Alex Robles ◽  
Madeleine Bayne ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Prevention And Treatment ◽  
Clade C ◽  
Hiv 1

scholarly journals A novel Schmallenberg virus subunit vaccine candidate protects IFNAR-/- mice against virulent SBV challenge

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hani Boshra ◽  
Gema Lorenzo ◽  
Diego Charro ◽  
Sandra Moreno ◽  
Gabriel Soares Guerra ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Clinical Signs ◽  
Interferon Γ ◽  
Schmallenberg Virus ◽  
Immune Protection ◽  
Large Ruminant ◽  
Economical Alternative

AbstractSchmallenberg virus (SBV), an arthropod-transmitted pathogenic bunyavirus, continues to be a threat to the European livestock industry, causing morbidity and mortality among young ruminant livestock. Here, we describe a novel SBV subunit vaccine, based on bacterially expressed SBV nucleoprotein (SBV-N) administered with a veterinary-grade Saponin adjuvant. When assayed in an IFNAR-/- mouse model, SBV-N with Saponin induced strong non-neutralizing broadly virus-reactive antibodies, decreased clinical signs, as well as significantly reduced viremia. Vaccination assays also suggest that this level of immune protection is cell mediated, as evidenced by the lack of neutralizing antibodies, as well as interferon-γ secretion observed in vitro. Therefore, based on these results, bacterially expressed SBV-N, co-administered with veterinary-grade Saponin adjuvant may serve as a promising economical alternative to current SBV vaccines, and warrant further evaluation in large ruminant animal models. Moreover, we propose that this strategy may be applicable to other bunyaviruses.

scholarly journals Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 213 ◽  
Author(s):  
Sigridur Jonsdottir ◽  
Victoria Fettelschoss ◽  
Florian Olomski ◽  
Stephanie C. Talker ◽  
Jelena Mirkovitch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Mononuclear Cells ◽  
Clinical Signs ◽  
T Cell Response ◽  
Type I ◽  
Cell Responses ◽  
Virus Like Particle ◽  
Ifn Γ

Background: Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly Culicoides bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMVTT) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. Objective: the preclinical and clinical safety of the eIL-5-CuMVTT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMVTT-specific IgG in the serum and plasma of vaccinated and unvaccinated horses. Further, peripheral blood mononuclear cells (PBMCs) from the same horses were re-stimulated in vitro for the proliferation and IFN-γ production of specific T cells. In addition, we evaluated longitudinal kidney and liver parameters and the general blood status. An endogenous protein challenge was performed in murine IL-5-vaccinated mice. Results: The vaccine was well tolerated as assessed by serum and cellular biomarkers and also induced reversible and neutralizing antibody titers in horses and mice. Endogenous IL-5 stimulation was unable to re-induce anti-IL-5 production. The CD4+ T cells of vaccinated horses produced significantly more IFN-γ and showed a stronger proliferation following stimulation with CuMVTT as compared to the unvaccinated controls. Re-stimulation using E. coli-derived proteins induced low levels of IFNγ+CD4+ cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Conclusions: Vaccination using eIL-5-CuMVTT induces a strong B-cell as well as CuMVTT-specific T cell response without the induction of IL-5-specific T cell responses. Hence, B-cell unresponsiveness against self-IL-5 can be bypassed by inducing CuMVTT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses.

scholarly journals A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 146 ◽  
Author(s):  
Michael Sieg ◽  
Johannes Busch ◽  
Maria Eschke ◽  
Denny Böttcher ◽  
Kristin Heenemann ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Peripheral Blood ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Clinical Signs ◽  
Primary Cells ◽  
Peripheral Blood Mononuclear ◽  
New Genotype ◽  
Genotype 2 ◽  
Permanent Cell

Paramyxoviruses comprise a large number of diverse viruses which in part give rise to severe diseases in affected hosts. A new genotype of feline morbillivirus, tentatively named feline morbillivirus genotype 2 (FeMV-GT2), was isolated from urine of cats with urinary tract diseases. Whole genome sequencing showed about 78% nucleotide homology to known feline morbilliviruses. The virus was isolated in permanent cell lines of feline and simian origin. To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. We demonstrate that FeMV-GT2 is able to infect renal and pulmonary epithelial cells, primary cells from the cerebrum and cerebellum, as well as immune cells in the blood, especially CD4+ T cells, CD20+ B cells and monocytes. The cats used for virus isolation shed FeMV-GT2 continuously for several months despite the presence of neutralizing antibodies in the blood. Our results point towards the necessity of increased awareness for this virus when clinical signs of the aforementioned organs are encountered in cats which cannot be explained by other etiologies.

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