Influenza virus vector iNS1 expressing bovine papillomavirus 1 (BPV1) antigens efficiently induces tumour regression in equine sarcoid patients

Bovine papillomaviruses types 1 and 2 (BPV1, BPV2) commonly induce skin tumours termed sarcoids in horses and other equids. Sarcoids seriously compromise the health and welfare of affected individuals due to their propensity to resist treatment and reoccur in a more severe form. We have developed influenza (Flu) A and B virus vectors that harbour a truncated NS1 gene (iNS) assuring interferon induction and co-express shuffled BPV1 E6 and E7 antigens for sarcoid immunotherapy. In a safety trial involving 12 healthy horses, intradermal administration of iNSA/E6E7equ and iNSB/E6E7equ was well tolerated, with the only transient side effect being mild fever in four horses. Repeated screening of secretions and faeces by RT-PCR and plaque assay revealed no virus shedding, thus also confirming biological safety. In a patient trial involving 29 horses bearing BPV1-induced single or multiple sarcoids, at least one lesion per horse was intratumourally injected and then boosted with iNSA/E6E7equ and/or iNSB/E6E7equ. The treatment induced a systemic antitumour response as reflected by the synchronous regression of injected and non-injected lesions. Irrespective of vaccination schemes, complete tumour regression was achieved in 10/29 horses. In 10/29 horses, regression is still ongoing (May 2021). Intriguingly, scrapings collected from former tumour sites in two patients tested negative by BPV1 PCR. Nine severely affected individuals with a history of unsuccessful therapeutic attempts did not (6/29) or only transiently (3/29) respond to the treatment. INSA/E6E7equ and iNSB/E6E7equ proved safe and effective in significantly reducing the tumour burden even in severe cases.

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Bovine papillomavirus load and mRNA expression, cell proliferation and p53 expression in four clinical types of equine sarcoid

Journal of General Virology ◽

10.1099/vir.0.82876-0 ◽

2007 ◽

Vol 88 (8) ◽

pp. 2155-2161 ◽

Cited By ~ 46

Author(s):

L. Bogaert ◽

M. Van Poucke ◽

C. De Baere ◽

J. Dewulf ◽

L. Peelman ◽

...

Keyword(s):

Viral Load ◽

Mrna Expression ◽

Bovine Papillomavirus ◽

P53 Expression ◽

Clinical Appearance ◽

Clinical Behaviour ◽

Equine Sarcoid ◽

Significant Difference ◽

Deep Layers ◽

E6 And E7

Equine sarcoids, the most common skin tumours in horses, are induced by bovine papillomavirus (BPV). Their clinical appearance varies from small stable patches to aggressively growing masses. Differences in BPV load and mRNA expression and Ki67 and p53 immunostaining among four clinical types (fibroblastic, occult, nodular and verrucous sarcoids) were evaluated to test the hypothesis that the clinical behaviour of equine sarcoids correlates with BPV activity. Viral load and expression of the BPV E2, E5, E6 and E7 genes were determined using quantitative real-time PCR. The proliferative fraction (PF) of the tumours was determined by Ki67 immunostaining and expression of p53 was analysed by immunohistochemistry. Nodular sarcoids showed a significantly higher viral load than the other types. A significant overall difference among the four types was observed for E2, E5, E6 and E7 mRNA expression. Nodular sarcoids showed the highest expression level for each BPV gene examined, followed by verrucous, fibroblastic and occult tumours. Viral DNA and mRNA outcomes correlated with each other, indicating a similar transcription pattern in each type of sarcoid. The PF was significantly higher in the superficial layers of verrucous and fibroblastic sarcoids compared with occult and nodular types. No significant difference was observed for the PF in the deep layers and for p53 expression. These results clearly demonstrate the omnipresence and active transcription of BPV in equine sarcoids. However, the hypothesis that the clinical behaviour of an equine sarcoid can be explained on the basis of differences in BPV activity could not be demonstrated.

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Immunotherapy of equine sarcoid: dose-escalation trial for the use of chimeric papillomavirus-like particles

Journal of General Virology ◽

10.1099/vir.0.83266-0 ◽

2008 ◽

Vol 89 (1) ◽

pp. 138-147 ◽

Cited By ~ 18

Author(s):

Stephanie Mattil-Fritz ◽

Doreen Scharner ◽

Konrad Piuko ◽

Nadja Thönes ◽

Lutz Gissmann ◽

...

Keyword(s):

Immune Responses ◽

Dose Escalation ◽

Clinical Status ◽

Surgical Excision ◽

Tumour Regression ◽

Causative Role ◽

Bovine Papillomavirus ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Equine Sarcoid

Equine sarcoids are fibrosarcoma-like skin tumours with a prevalence of approximately 1–2 %. Strong evidence exists for a causative role of bovine papillomavirus (BPV) type 1 or type 2 in the development of sarcoids. No effective treatment of equine sarcoid is available and after surgical excision relapse of the tumours is very frequent. We developed chimeric virus-like particles (CVLPs) of BPV 1 L1–E7 for the immunotherapy of equine sarcoid. In a phase I clinical trial 12 horses suffering from equine sarcoid with an average number of more than 22 tumours per animal were vaccinated in a dose-escalation setting. The animals were followed-up for 63 days, eight of the twelve horses were followed-up for more than a year and side-effects, humoral immune responses and tumour appearance were recorded. BPV DNA was detected in tumours of 11 cases. CVLPs were well tolerated in all dose groups, a robust anti-L1 antibody response was induced in all but one of the horses. Anti-E7 antibodies were detected in five of the 12 animals at low titres. Two animals showed a clear improvement of the clinical status after treatment, i.e. the number of the tumours per horse was reduced. In another horse regression of five sarcoids was observed; three of them relapsed during the study. Two animals showed tumour regression as well as growth of new sarcoids. In two horses the clinical status remained unchanged, in another two horses growth of existing tumours or growth of additional tumours was observed. The remaining three animals showed simultaneously regression and growth of existing tumours. Neither the humoral immune responses nor the observed effects on the tumours was correlated with the dose group.

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Open reading frames E6 and E7 of bovine papillomavirus type 1 are both required for full transformation of mouse C127 cells.

Journal of Virology ◽

10.1128/jvi.63.1.259-266.1989 ◽

1989 ◽

Vol 63 (1) ◽

pp. 259-266 ◽

Cited By ~ 36

Author(s):

K Neary ◽

D DiMaio

Keyword(s):

Open Reading Frames ◽

Bovine Papillomavirus ◽

Full Transformation ◽

E6 And E7 ◽

Reading Frames

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Detection and characterisation of papillomavirus in skin lesions of giraffe and sable antelope in South Africa

Journal of the South African Veterinary Association ◽

10.4102/jsava.v82i2.39 ◽

2011 ◽

Vol 82 (2) ◽

Cited By ~ 12

Author(s):

E. Van Dyk ◽

A-M Bosman ◽

E. Van Wilpe ◽

J. H. Williams ◽

R. G. Bengis ◽

...

Keyword(s):

Real Time ◽

Real Time Pcr ◽

Skin Lesions ◽

Immunoperoxidase Staining ◽

Bovine Papillomavirus ◽

Virus Particles ◽

Tissue Sections ◽

Equine Sarcoid ◽

Pcr Product ◽

Papillomavirus Dna

Papillomavirus was detected electron microscopically in cutaneous fibropapillomas of a giraffe (Giraffa camelopardalis) and a sable antelope (Hippotragus niger). The virus particles measured 45 nm in diameter. Histopathologically, the lesions showed histopathological features similar to those of equine sarcoid as well as positive immunoperoxidase-staining of tissue sections for papillomavirus antigen. Polymerase chain reaction (PCR) detected bovine papillomavirus (BPV) DNA. Bovine papillomavirus-1 was characterised by real-time PCR in the sable and giraffe, and cloning and sequencing of the PCR product revealed a similarity to BPV-1. As in the 1st giraffe, the lesions from a 2nd giraffe revealed locally malignant pleomorphism, possibly indicating the lesional end-point of papilloma infection. Neither virus particles nor positively staining papillomavirus antigen could be demonstrated in the 2nd giraffe but papillomavirus DNA was detected by real-time PCR which corresponded with BPV-1 and BPV-2.

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Infectious Keratitis in Western Nepal: An Experience from a Tertiary Care Hospital

10.21203/rs.2.125/v1 ◽

2018 ◽

Author(s):

Rajani Shrestha ◽

Niranjan Nayak ◽

Babita Gurung ◽

Shishir Gokhale

Keyword(s):

Antibiotic Susceptibility ◽

Fungal Growth ◽

Severe Form ◽

Fungal Keratitis ◽

Clinical Severity ◽

Diffusion Method ◽

Eye Drops ◽

Infectious Keratitis ◽

History Of ◽

Predisposing Conditions

Abstract Background: Corneal blindness is a major public health problem worldwide and infectious keratitis is one of its leading causes. The aim was is to analyze the microbial etiology of corneal ulcers and to determine the antibiotic susceptibility pattern of bacterial isolates in order to find out the existing drug resistance pattern. Methods: Corneal scrapings were collected as per the standard procedure. All the isolates were identifies by conventional microbiological techniques. Antibiotic susceptibility testing was performed using disc diffusion method. Clinical grading of the ulcerative lesion was carried out by the recommended protocol. Results: Among the 84 cases of clinically diagnosed infectious keratitis investigated, 33 (39.3%) were farmers by occupation. All cases were reviewed for predisposing conditions and clinical severity. Ulcers were categorized as mild in 49 cases moderate in 12 and severe in 23 cases. Predisposing conditions were found in 55(65.5%) of the 84 cases. Forty-two cases showed culture positivity. Among these 42; 25 (29.7%) yielded fungal growth, 13(30.1%) yielded bacteria and the rest 4 (4.7%) showed mixed growth. Aspergillus spp. (10/29; 34.5%) were the commonest fungi isolated followed by Fusarium spp. (6/29; 20%). Similarly, Staphylococcus aureus, (8/17; 47%) was the most common among bacteria. Majority i.e 66.7% (26 of 39) of those having trauma, as the predisposing factor developed moderate to severe degree of corneal ulceration as compared to only 20% (9 of 45) of those without any history of trauma. (p<0.001). Interestingly, 20(68.9%) of the 29 cases that had yielded fungal growth on culture had had previous history of ocular trauma in contrast to only 19 (34.5%) of the 55 who had non-fungal origin of keratitis. (p=0.003). Fungal keratitis cases presented with more severe form of ulcerative lesions exhibiting more often with infiltrates and hypopion as compared to bacterial keratitis. Topical administration of fourth generation fluoroquinolone eye drops remained the most effective drug of choice with clinical improvement in all cases without any complications. Conclusions: Trauma with vegetative matter predisposed to most cases of fungal keratitis. Severe form of ulceration was noticed in patients with fungal infection. Surveillance of the antibiotic sensitivity is needed for quality patient management.

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Ophthalmic Artery Occlusion From Injection of Heroin Into the Forehead

Journal of VitreoRetinal Diseases ◽

10.1177/2474126419854276 ◽

2019 ◽

Vol 3 (4) ◽

pp. 260-262

Author(s):

Pimpiroon Ploysangam ◽

Faruk Koreishi ◽

Gareth M.C. Lema

Keyword(s):

Optical Coherence Tomography ◽

Ophthalmic Artery ◽

Optical Coherence Tomography Angiography ◽

Artery Occlusion ◽

Severe Form ◽

Optical Coherence ◽

Retrospective Case ◽

Retinal Hemorrhages ◽

Disc Hemorrhage ◽

History Of

Purpose: To report a case of ophthalmic artery occlusion after injection of heroin into the forehead. Methods: Retrospective case report. Results: A 27-year-old patient with a history of intravenous heroin abuse presented with a left ophthalmic artery occlusion after attempting to inject heroin into a vein in her forehead. Exam was significant for diffuse retinal edema, disc edema, disc hemorrhage, and diffuse retinal hemorrhages. Findings were also noted in the widefield image, optical coherence tomography, and optical coherence tomography angiography of the retina. Conclusions: This patient suffered from a severe form of talc retinopathy resulting in an ophthalmic artery occlusion after injecting heroin into her forehead. To our knowledge, this is the first instance of combined ophthalmic artery occlusion and talc retinopathy resulting from intentional injection into a superficial facial vein.

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Acne Conglobata Associated with Hidradenitis Suppurativa, Disorders of Follicular Occlusion (Case Report)

Acta Medica Martiniana ◽

10.1515/acm-2015-0009 ◽

2015 ◽

Vol 15 (2) ◽

pp. 30-34

Author(s):

K. Pecova

Keyword(s):

Hidradenitis Suppurativa ◽

Severe Form ◽

Term Treatment ◽

Acne Conglobata ◽

Long Term Treatment ◽

Associated Symptoms ◽

History Of ◽

Inflammatory Bowel ◽

Prepubertal Age

Abstract The author is presenting the case of a 23-year-old female patient with a severe form of acne conglobata, with the first symptoms of the disease occurring as far back as the prepubertal age. In the past year the disease has combined with hidradenitis suppurativa (to be referred to henceforth as “HS”), Hurley stage I, in the axillae and both sides of the inguinal region, with a family history of acne conglobata (both her mother and brother were affected). Further examinations ruled out inflammatory bowel disease because of a lack of further associated symptoms, except for sideropenic anaemia (lesser form) and lower serum values of vitamin D. Up until now the disease has been resistant to treatment, including the long-term treatment of methylprednisolone in combination with isotretinoid as well as dapsone and antibiotics.

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Emphysematous pyelonephritis with Dengue hemorrhagic fever: A successful medical management of a fatal scenario

Asian Journal of Medical Sciences ◽

10.3126/ajms.v8i5.17847 ◽

2017 ◽

Vol 8 (5) ◽

pp. 101-103

Author(s):

Robin George Manappallil ◽

Prathap Reddy Muthyala

Keyword(s):

Dengue Fever ◽

Hemorrhagic Fever ◽

Severe Form ◽

Medical Sciences ◽

Emphysematous Pyelonephritis ◽

Associated Gas ◽

Acute Necrotizing ◽

Life Threatening ◽

History Of ◽

Plasma Leakage

Emphysematous pyelonephritis is a life threatening acute necrotizing infection with associated gas formation involving the renal parenchyma and perinephric tissues. Dengue fever, according to the WHO, is the most rapidly spreading mosquito borne viral infection in the world. Dengue Hemorrgahic Fever is a more severe form of dengue fever and is characterized by fever, bleeding manifestations, plasma leakage and thrombocytopenia. This is a case of a 56 year old female, who presented with history of fever, headache, myalgia and dysuria; and was diagnosed to have emphysematous pyelonephritis with Dengue Hemorrgahic Fever. She was successfully managed with intravenous antibiotics and platelet transfusions, without any urological interventions. Asian Journal of Medical Sciences Vol.8(5) 2017 101-103

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