Rapid and Durable Protection Against Marburg Virus with a Single-Shot ChAd3-MARV GP Vaccine

Marburg virus (MARV) causes a severe hemorrhagic fever disease in primates with mortality rates in humans up to 90%. Since 2018, MARV has been identified as a priority pathogen by the WHO, needing urgent research and development of countermeasures due to the high public health risk it poses. Recently, the first case of MARV in West Africa underscored the significant outbreak potential of this virus. The potential for cross border spread as had occurred during the Ebola 2014-2016 outbreak illustrates the critical need for Marburg vaccines. To support regulatory approval of the ChAd3-Marburg vaccine that has completed Phase I trials, we show that a non-replicating chimpanzee-derived adenovirus vector with a demonstrated safety profile in humans (ChAd3) protected against a uniformly lethal challenge with Marburg-Angola. Protective immunity was achieved within 7 days of vaccination and was maintained through one year post vaccination, antigen-specific antibodies were a significant immune correlate of protection in the acute challenge model (p=0.0003), and predictive for protection with an AUC = 0.88. These results demonstrate that a single-shot ChAd3 MARV vaccine generated a protective immune response that was both rapid and durable with a significant immune correlate of protection that will support advanced clinical development.

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Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus

Journal of Virology ◽

10.1128/jvi.00561-09 ◽

2009 ◽

Vol 83 (14) ◽

pp. 7296-7304 ◽

Cited By ~ 168

Author(s):

Thomas W. Geisbert ◽

Joan B. Geisbert ◽

Anders Leung ◽

Kathleen M. Daddario-DiCaprio ◽

Lisa E. Hensley ◽

...

Keyword(s):

Nonhuman Primates ◽

Ebola Virus ◽

Single Injection ◽

Hemorrhagic Fever ◽

Marburg Virus ◽

Lethal Challenge ◽

Glycoprotein G ◽

Unvaccinated Control ◽

Zaire Ebolavirus ◽

Vesicular Stomatitis

ABSTRACT The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSVΔG/SEBOVGP, VSVΔG/ZEBOVGP, and VSVΔG/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSVΔG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species.

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Protection of Nonhuman Primates against Two Species of Ebola Virus Infection with a Single Complex Adenovirus Vector

Clinical and Vaccine Immunology ◽

10.1128/cvi.00467-09 ◽

2010 ◽

Vol 17 (4) ◽

pp. 572-581 ◽

Cited By ~ 71

Author(s):

William D. Pratt ◽

Danher Wang ◽

Donald K. Nichols ◽

Min Luo ◽

Jan Woraratanadharm ◽

...

Keyword(s):

Nonhuman Primates ◽

Ebola Virus ◽

Adenovirus Vector ◽

Hemorrhagic Fever ◽

Lethal Challenge ◽

Highly Pathogenic ◽

Pathogenic Viruses ◽

Single Complex ◽

Zaire Ebolavirus ◽

Ebola Virus Infection

ABSTRACT Ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. To meet the need for a vaccine against the several types of Ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (EBO7) that expresses the glycoproteins of Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV) in a single complex adenovirus-based vector (CAdVax). We evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes of lethal challenge. EBO7 vaccine provided protection against both Ebola viruses by either route of infection. Significantly, protection against SEBOV given as an aerosol challenge, which has not previously been shown, could be achieved with a boosting vaccination. These results demonstrate the feasibility of creating a robust, multivalent Ebola virus vaccine that would be effective in the event of a natural virus outbreak or biological threat.

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AB0310 TOLERABILITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME, PRELIMINARY RESULTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1447 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1180.3-1181

Author(s):

G. Tarasova ◽

B. Belov ◽

M. Cherkasova ◽

E. Aseeva ◽

T. Reshetnyak ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Pneumococcal Vaccine ◽

Respiratory Infections ◽

Vascular Complications ◽

Initial Increase ◽

Post Vaccination ◽

Preliminary Results ◽

One Year ◽

Polysaccharide Pneumococcal Vaccine

Background:Antiphospholipid syndrome (APS) is an autoimmune disease often associated with severe, life-threatening vascular complications. The majority of patients (and in case of secondary APS, in 100% of cases) receive immunosuppressive therapy. Immunization with pneumococcal vaccines in patients with both primary APS (PAPS) and APS+SLE or secondary (sAPS) is necessary to prevent severe respiratory infections in these patients.Objectives:Purpose of the study - to study the tolerance and safety of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with PAPS and sAPS.Methods:At this stage, the study included 28 patients with APS, of which 10 with PAPS, 18 with sAPS proceeding against the background of systemic lupus erythematosus (SLE), of which 23 women (82%), 5 men (18%). The average age (Me) of patients was 43 (35.5; 53.0) g. 20 patients received glucocorticoids (GC) 5-30 mg/day equivalent to prednisone, 17- hydroxychloroquine, 6- cytostatics (3-cyclophosphamide, 2-azathioprine, 1- mycophenolate mofetil), 8- biologics: 5-rituximab (RTM), 3-belimumab (BLM); 20-received anticoagulants (direct-10, indirect-10).1 dose (0.5 ml) of PPV-23 was administered subcutaneously. The follow-up time was 1 year in 23 patients and 5-5.5 months in 5-5.5 months. During the visits, standard clinical and laboratory tests were performed, immunological blood test and the level of antibodies to S.pneumoniaeResults:Vaccination was well tolerated in all patients. In 29% of cases, vaccine reactions of mild severity were observed: in 7 (25%) - a local reaction (pain in the arm for 1-3 days-at 7, redness up to 2 cm at the injection site-at 1), in 1 (3,6%), the patient experienced general weakness (moderately pronounced) for 1 month. Vaccinal reactions were completely reversible and did not require additional prescriptions. Post-vaccination complications develop, as a rule, in the first 1-2 months after vaccination. During the observation period, none of the patients had an exacerbation of the disease, reliably associated with the vaccination. There was no recurrence of thrombosis, both in patients receiving anticoagulant therapy and without it. No new autoimmune phenomena, both clinical and laboratory, were identified. The dynamics of the production of anti-streptococcal antibodies during the year was followed in 16 patients. One year after vaccination, 31% of patients showed a significant (more than 2-fold compared to the initial) increase in the concentration of antibodies to polysaccharides of the cell wall of S. pneumoniae (“responders”), 69% of patients were “non-responders” to the vaccine. At the same time, all 5 patients with PAPS were “non-responders”, and 45.5% “respondents” with sAPS.Conclusion:Preliminary results show that patients with APS tolerate PPV-23 vaccination well. In the next post-vaccination period, exacerbations of the disease, thrombosis were not recorded. Attention is drawn to the large number of “non-responders” in PAPS, however, to obtain statistically reliable results, it is necessary to continue the study and recruit more patients.Disclosure of Interests:None declared

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Development and Validation of 13-plex Luminex-Based Assay for Measuring Human Serum Antibodies to Streptococcus pneumoniae Capsular Polysaccharides

mSphere ◽

10.1128/msphere.00128-18 ◽

2018 ◽

Vol 3 (4) ◽

pp. e00128-18 ◽

Cited By ~ 9

Author(s):

Danka Pavliakova ◽

Peter C. Giardina ◽

Soraya Moghazeh ◽

Shite Sebastian ◽

Maya Koster ◽

...

Keyword(s):

Human Serum ◽

Lower Limit ◽

Immunosorbent Assay ◽

Enzyme Linked Immunosorbent Assay ◽

Igg Antibodies ◽

Igg Antibody ◽

Correlate Of Protection ◽

Immune Correlate ◽

Relative Standard ◽

Limit Of Quantitation

ABSTRACT A Luminex-based direct immunoassay (dLIA) platform has been developed to replace the standardized pneumococcal enzyme-linked immunosorbent assay platform. The multiplex dLIA simultaneously measures the concentration of serum immunoglobulin G (IgG) antibodies specific for pneumococcal capsular polysaccharide (PnPS) serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. The assay uses poly-l-lysine (PLL)-conjugated PnPS, chemically coupled to spectrally distinct Luminex microspheres. Assay validation experiments were performed using residual human serum samples obtained from 13-valent pneumococcal conjugate vaccine (13vPnC) clinical studies. Assay results are expressed as IgG antibody concentrations in micrograms per milliliter using the international reference serum, 007sp. The lower limit of quantitation (LLOQ) for all serotypes covered in the 13-plex dLIA fell within the range of 0.002 to 0.038 µg/ml serum IgG. The difference between the lower limit and upper limit of the assay range was >500-fold for all serotypes, and assay variability was <20% relative standard deviation (RSD) for all serotypes. IgG antibody measurements were shown to be serotype-specific (some cross-reactivity was observed only between the structurally related serotypes 6A and 6B as well as 19A and 19F), and no interference was observed between the serotypes when the assay was performed in the 13-plex format compared to the singleplex assays. The 13-plex dLIA platform developed by Pfizer Inc. generates up to 143 test results in a single 96-well plate and is a suitable replacement of the enzyme-linked immunosorbent assay (ELISA) platform for evaluating vaccine clinical trials. IMPORTANCE The pneumococcal enzyme-linked immunosorbent assay (ELISA) measures IgG antibodies in human serum, and it is an important assay that supports licensure of pneumococcal vaccines. The immune correlate of protection, 0.35 µg/ml of IgG antibodies, was determined by the ELISA method. Pfizer has developed a new Luminex-based assay platform to replace the ELISA. These papers describe the important work of (i) validating the Luminex-based assay and (ii) bridging the immune correlate of protection (0.35 µg/ml IgG) to equivalent values reported by the Luminex platform.

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Serological response to rabies virus induced by commercial vaccines in cattle

Ciência Rural ◽

10.1590/0103-8478cr20161044 ◽

2017 ◽

Vol 47 (10) ◽

Author(s):

Mathias Martins ◽

João Motta de Quadros ◽

Eduardo Furtado Flores ◽

Rudi Weiblen

Keyword(s):

Rabies Virus ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Booster Vaccination ◽

Serological Response ◽

Serum Samples ◽

Anamnestic Response ◽

Post Vaccination ◽

Antibody Titers ◽

One Year

ABSTRACT: The antibody response to rabies virus (RABV) induced by commercial vaccines in heifers was investigated. For this, 84 heifers were vaccinated twice (30 days interval) with each of four vaccines (G1 = 14 animals; G2 = 24; G3 = 22 and G4 = 24) and received a booster vaccination 360 days later. Serum samples collected at different intervals after vaccination and 30 days after booster were submitted to a virus neutralizing (VN) assay for RABV antibodies. Thirty days after the second vaccine dose, 92% of the immunized animals presented VN titers ≥0.5UI/mL (geometric medium titers [GMT] 1.7 to 3.8UI/mL). At the day of the booster (360 days post-vaccination); however, the percentage of animals harboring antibody titers ≥0.5UI/mL had dropped to 31% (0-80% of the animals, depending on the vaccine), resulting in lower GMT (0.1 to 0.6UI/mL). Booster vaccination at day 360 resulted in a detectable anamnestic response in all groups, resulting in 83% of animals (65 to 100%) harboring VN titers ≥0.5UI/mL thirty days later (GMT 0.6 to 4.3UI/mL). These results indicated that these vaccines were able to induce an adequate anti-RABV response in all animals after prime vaccination (and after booster as well). However, the titers decreased, reaching titers <0.5UI/mL in approximately 70% of animals within the interval before the recommended booster. Thus, booster vaccination for rabies in cattle using the current vaccines should be performed before the recommended one-year interval, as to maintain neutralizing antibodies levels in most vaccinated animals.

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An Unsual Site about Small Cells Osteosarcoma Parietal Region and Classique Osteosarcoma Occipital Region Mimicking Meningioma with Literature Review Management and Outcome

Advances in Neurology and Neuroscience ◽

10.33140/an.02.01.09 ◽

2019 ◽

Vol 2 (1) ◽

Keyword(s):

Correct Diagnosis ◽

Small Cell ◽

Small Cells ◽

Long Bones ◽

Unusual Site ◽

First Case ◽

Review Management ◽

Similar Materials ◽

One Year ◽

Age Range

Introduction: Primary osteosarcoma (OS) is the second most common primary bone malignancy, the first being multiple myeloma. OS occurs in the second decade, with a predilection for ends of long bones. Head and neck involvement is seen in 2-9% with extragnathic craniofacial bones in 1–2% of cases. Small Cell OS (SCO) constitutes 1.3-4% of all OS, skeletal distribution and age range being similar. Materials and Methods: We report two rare osteosarcoma and we done the review of the literature about the management and the outcome about intracranial osteosarcoma in our department of neurosurgery. Results: It is two osteosarcoma cases about a 72-year-old man and one 49-year-old man who both mimiking first meningioma. The first case is an unusual site parietal and the second case is occipital. The both benefited surgery with excision and exam of histology confirm diagnosis. But the first case died 15 days after surgery in intensive unit care and the second cases died after one year, he benefited surgery and chemotherapy. Conclusion: Small cell osteosarcoma (SCO) is an extremely uncommon entity that mainly involves the metaphysics of long bones and, rarely, the skull. Histopathology is the key to establishing the correct diagnosis, including sub typing for appropriate management and prognostication, as radiological features are not specific.

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Habitual Stone-Tool Aided Extractive Foraging in White-Faced Capuchins, Cebus Capucinus

10.1101/351619 ◽

2018 ◽

Author(s):

Brendan J Barrett ◽

Claudio M Monteza-moreno ◽

Tamara DOGANDŽIĆ ◽

Nicolas Zwyns ◽

Alicia IBÁÑEZ ◽

...

Keyword(s):

Tool Use ◽

National Park ◽

Resource Limitation ◽

Stone Tools ◽

Cebus Capucinus ◽

Hermit Crabs ◽

Stone Tool ◽

Extractive Foraging ◽

First Case ◽

One Year

ABSTRACTHabitual reliance on tool use is a marked behavioral difference between wild robust (genus Sapajus) and gracile (genus Cebus) capuchin monkeys. Despite being well studied and having a rich repertoire of social and extractive foraging traditions, Cebus sp have rarely been observed engaging in tool use and have never been reported to use stone tools. In contrast, habitual tool use and stone-tool use by Sapajus is widespread. We discuss factors which might explain these differences in patterns of tool use between Cebus and Sapajus. We then report the first case of habitual stone-tool use in a gracile capuchin: a population of white-faced capuchins (Cebus capucinus imitator) in Coiba National Park, Panama who habitually rely on hammerstone and anvil tool use to access structurally protected food items in coastal areas including Terminalia catappa seeds, hermit crabs, marine snails, terrestrial crabs, and other items. This behavior has persisted on one island in Coiba National Park since at least 2004. From one year of camera trapping, we found that stone tool use is strongly male-biased. Of the 205 unique camera-trap-days where tool use was recorded, adult females were never observed to use stone-tools, although they were frequently recorded at the sites and engaged in scrounging behavior. Stone-tool use occurs year-round in this population, and over half of all identifiable individuals were observed participating. At the most active tool use site, 83.2% of days where capuchins were sighted corresponded with tool use. Capuchins inhabiting the Coiba archipelago are highly terrestrial, under decreased predation pressure and potentially experience resource limitation compared to mainland populations– three conditions considered important for the evolution of stone tool use. White-faced capuchin tool use in Coiba National Park thus offers unique opportunities to explore the ecological drivers and evolutionary underpinnings of stone tool use in a comparative within- and between-species context.

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An analysis of early morning acth levels in the first case of pembrolizumab-induced adrenalitis as a delayed immune-related event (dire) – case study

Wiadomości Lekarskie ◽

10.36740/wlek202002136 ◽

2020 ◽

Vol 73 (2) ◽

pp. 396-400

Author(s):

Igor Alexander Harsch ◽

Anastasiia Gritsaenko ◽

Peter Christopher Konturek

Keyword(s):

Replacement Therapy ◽

Early Morning ◽

Related Event ◽

Special Situation ◽

Melanocyte Stimulating Hormone ◽

First Case ◽

Life Threatening ◽

Dual Release ◽

One Year

The aim: The levels of adrenocorticotrophic hormone (ACTH) are elevated in primary adrenal failure (Addison’s disease) with a peak in the early morning hours. This also occurs under hydrocortisone replacement therapy due to the unphysiological substitution regime. The aim was to study ACTH levels under two different replacement regimens. This is exemplified in a patient with adrenalitis after immunotherapy for malignant melanoma (MM), since (elevated) levels of ACTH and its cleavage product alpha-melanocyte stimulating hormone (α-MSH) raise concerns since receptors for both hormones can be expressed in melanoma cells. Material and methods: A female with MM had immunotherapy with pembrolizumab and developed adrenalitis with Addison crisis about one year after discontinuation of this therapy (delayed immune-related event = DIRE). ACTH levels were measured hourly (4-8 a.m.) during a “conventional” hydrocortisone replacement therapy and during a therapy with dual-release hydrocortisone. Results: Salient differences between the morning ACTH profiles under the “conventional” hydrocortisone replacement regimen with 10-5-5 mg/die compared to the single-dose regimen with 20 mg dual-release hydrocortisone were not discernible. Conclusion: DIRE could be an underestimated problem in immunotherapy and could put the patients at hazard. Especially in case of an endocrinological DIRE concerning the adrenocorticotrophic axis, life-threatening situations can arise for the patients. As for the special situation with M. Addison and MM, where hormonal feedback mechanisms may cause further problems beyond the normal hormonal replacement therapy, we observed no salient differences in the early morning ACTH profiles under different hydrocortisone replacement regimens.

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Monetary Policy Report - January 2021

10.32468/inf-pol-mont-eng.tr1.-2021 ◽

2021 ◽

Author(s):

◽

...

Keyword(s):

Consumer Price Index ◽

Fourth Quarter ◽

Inflation Expectations ◽

Forecast Horizon ◽

Core Inflation ◽

Expected Inflation ◽

First Case ◽

Downward Pressure ◽

Domestic Prices ◽

One Year

Macroeconomic Summary Overall inflation (1.61%) and core inflation (excluding food and regulated items) (1.11%) both declined beyond the technical staff’s expectations in the fourth quarter of 2020. Year-end 2021 forecasts for both indicators were revised downward to 2.3% and 2.1%, respectively. Market inflation expectations also fell over this period and suggested inflation below the 3% target through the end of this year, rising to the target in 2022. Downward pressure on inflation was more significant in the fourth quarter than previously projected, indicating weak demand. Annual deceleration among the main groups of the consumer price index (CPI) was generalized and, except for foods, was greater than projected in the October report. The CPI for goods (excluding foods and regulated items) and the CPI for regulated items were subject to the largest decelerations and forecasting discrepancies. In the first case, this was due in part to a greater-than-expected effect on prices from the government’s “VAT-fee day” amid weak demand, and from the extension of some price relief measures. For regulated items, the deceleration was caused in part by unanticipated declines in some utility prices. Annual change in the CPI for services continued to decline as a result of the performance of those services that were not subject to price relief measures, in particular. Although some of the overall decline in inflation is expected to be temporary and reverse course in the second quarter of 2021, various sources of downward pressure on inflation have become more acute and will likely remain into next year. These include ample excesses in capacity, as suggested by the continued and greater-than-expected deceleration in core inflation indicators and in the CPI for services excluding price relief measures. This dynamic is also suggested by the minimal transmission of accumulated depreciation of the peso on domestic prices. Although excess capacity should fall in 2021, the decline will likely be slower than projected in the October report amid additional restrictions on mobility due to a recent acceleration of growth in COVID-19 cases. An additional factor is that low inflation registered at the end of 2020 will likely be reflected in low price adjustments on certain indexed services with significant weight in the CPI, including real estate rentals and some utilities. These factors should keep inflation below the target and lower than estimates from the previous report on the forecast horizon. Inflation is expected to continue to decline to levels near 1% in March, later increasing to 2.3% at the end of 2021 and 2.7% at year-end 2022 (Graph 1.1). According to the Bank’s most recent survey, market analysts expect inflation of 2.7% and 3.1% in December 2021 and 2022, respectively. Expected inflation derived from government bonds was 2% for year-end 2021, while expected inflation based on bonds one year forward from that date (FBEI 1-1 2022) was 3.2%.

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Pandemic 2011: coming soon to a location near you.

10.32920/ryerson.14645865.v1 ◽

2021 ◽

Author(s):

Jennifer Sacco

Keyword(s):

Media Coverage ◽

World Health ◽

First Case ◽

The World ◽

Spanish Flu ◽

Seasonal Flu ◽

The Media ◽

One Year ◽

Health Organization ◽

Lower Death Rate

"H1 N1 is a virus that has been sensationalized by the media since the first case was discovered in Mexico during the spring of 2009. People around the world feared that the virus would mutate into something as severe as the 1918 Spanish flu, one of the deadliest plagues in history. However experts had discovered by June of 2009 that the Spanish flu was not comparable to H1 N1. Yet for six months newspaper reporters continued to compare the ew epidemic to the Spanish flu, thus keeping alive the threat of an unstoppable pandemic. One year has passed since the first case of H1 N1 was confirmed. After all of the attention that H1 N1 received, it proved to be not much different than a typical seasonal flu, resulting in a lower death rate (Schabas and Rau, 2010). Recently, a number of investigations have begun to determine if the World Health Organization (WHO) overemphasized the level of risk, resulting in a large quantity of sensationalized media coverage, and citizens in a state of panic.

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