scholarly journals Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge

2019 ◽  
Vol 11 (494) ◽  
pp. eaau9242 ◽  
Author(s):  
Michael K. Lo ◽  
Friederike Feldmann ◽  
Joy M. Gary ◽  
Robert Jordan ◽  
Roy Bannister ◽  
...  

Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection.

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 133 ◽  
Author(s):  
Maria S. Salvato ◽  
Arban Domi ◽  
Camila Guzmán-Cardozo ◽  
Sandra Medina-Moreno ◽  
Juan Carlos Zapata ◽  
...  

Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4+ and CD8+ T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.


2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S431-S435 ◽  
Author(s):  
Abhishek N Prasad ◽  
Krystle N Agans ◽  
Satheesh K Sivasubramani ◽  
Joan B Geisbert ◽  
Viktoriya Borisevich ◽  
...  

Abstract The high case-fatality rates and potential for use as a biological weapon make Nipah virus (NiV) a significant public health concern. Previous studies assessing the pathogenic potential of NiV delivered by the aerosol route in African green monkeys (AGMs) used the Malaysia strain (NiVM), which has caused lower instances of respiratory illness and person-to-person transmission during human outbreaks than the Bangladesh strain (NiVB). Accordingly, we developed a small particle aerosol model of NiVB infection in AGMs. Consistent with other mucosal AGM models of NiVB infection, we achieved uniform lethality and disease pathogenesis reflective of that observed in humans.


2012 ◽  
Vol 4 (146) ◽  
pp. 146ra107-146ra107 ◽  
Author(s):  
K. N. Bossart ◽  
B. Rockx ◽  
F. Feldmann ◽  
D. Brining ◽  
D. Scott ◽  
...  

2021 ◽  
Author(s):  
Neeltje van Doremalen ◽  
Victoria Avanzato ◽  
Friederike Feldmann ◽  
Jonathan Schulz ◽  
Elaine Haddock ◽  
...  

Nipah virus (NiV) is a highly pathogenic and re-emerging virus which causes sporadic but severe infections in humans. Currently, no vaccines against NiV have been approved. We previously showed that ChAdOx1 NiV provides full protection against a lethal challenge with NiV Bangladesh (NiV-B) in hamsters. Here, we investigated the efficacy of ChAdOx1 NiV in the lethal African green monkeys (AGMs) NiV challenge model. AGMs were vaccinated either 4 weeks before challenge (prime vaccination), or 8 and 4 weeks before challenge with ChAdOx1 NiV (prime-boost vaccination). A robust humoral and cellular response was detected starting 14 days post initial vaccination. Upon challenge, control animals displayed a variety of signs and had to be euthanized between 5- and 7-days post inoculation. In contrast, vaccinated animals showed no signs of disease, and we were unable to detect infectious virus in all but one swab and all tissues. Importantly, no to limited antibodies against fusion protein or nucleoprotein IgG could be detected 42 days post challenge, suggesting that vaccination induced a very robust protective immune response preventing extensive virus replication.


Author(s):  
Kanniyan Binub

Background: A recent epidemic of Nipah virus affected few districts of Malabar in Kerala, Southern India. Eighteen people died, remarking case fatality rate of 94.7%. Early diagnosis within second case by doctors and prompt control activities by the health ministry saved more lives. Objective was to study knowledge and attitude about Nipah among medical students of Malappuram District.Methods: The study was conducted among 200 MBBS students of tertiary medical college at Malappuram district, North Kerala. A pre structured questionnaire was used to study on knowledge and attitude related to Nipah among medical. Then the data was collected, analyzed and entered into Excel. The frequency of awareness among medical students was expressed in proportions.Results: Majority had good attitude and half of them had good knowledge about the disease. Most of students have been aware about the virus by social media (40.5%) as major source of information followed by news/newspaper (34%), (17.5 %) internet and (8%) by awareness programs.Conclusions: Topic about Nipah virus disease should be inculcated in medical textbooks elaborately. Special training programs for medical students should be on focus and health education sessions should be enhanced. 


Vaccine ◽  
2015 ◽  
Vol 33 (24) ◽  
pp. 2823-2829 ◽  
Author(s):  
Joseph Prescott ◽  
Blair L. DeBuysscher ◽  
Friederike Feldmann ◽  
Donald J. Gardner ◽  
Elaine Haddock ◽  
...  

2020 ◽  
Vol 14 (12) ◽  
pp. e0008910
Author(s):  
Huixin Chen ◽  
Nyo Min ◽  
Luyao Ma ◽  
Chee-Keng Mok ◽  
Justin Jang Hann Chu

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that is responsible for numerous large and geographical epidemics, causing millions of cases. However, there is no vaccine or therapeutics against CHIKV infection available. Interferon-alpha (IFN-α) has been shown to produce potent antiviral responses during viral infection. Herein we demonstrated the use of an adenovirus-vectored expressed mouse IFN-α (mDEF201) as a prophylactic and therapeutic treatment against CHIKV in vivo. 6-day-old BALB/c mice were pre- or post-treated intranasally with single dose of mDEF201 at 5 x 106 PFU per mouse and challenged with lethal dose of CHIKV. Complete survival protection was observed in mice upon a single dose of mDEF201 administration 1 days prior to virus challenge. Viral load in the serum and multiple organs were significantly reduced upon mDEF201 administration in a dose dependent manner as compare with adenovirus 5 vector placebo set. Histological analysis of the mice tissue revealed that mDEF201 could significantly reduce the tissue morphological abnormities, mainly infiltration of immune cells and muscle fibre necrosis caused by CHIKV infection. In addition, administration of mDEF201 at 6 hours post CHIKV challenge also showed promising inhibitory effect against viral replication and dissemination. In conclusion, single-dose of intranasal administration with mDEF201 as a prophylactic or therapeutic agent within 6 hours post CHIKV infection is highly protective against a lethal challenge of CHIKV in the murine model.


Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Prafulla Kumar Swain

Background: In this paper an attempt has been made to estimate the Case Fatality Ratio (CFR) for coronavirus disease of India and few selected countries. and Also, highlighted the pros and cons of obtaining crude and adjusted CFR of COVID-19 pandemic. Material and Methods: Data extracted from WHO situation report and University of Oxford website have been used for this analysis. The CFR and its 95% confidence interval were computed, trend and bar plot was used for graphical representation. Results: The worldwide crude CFR stands 6.73% (95% CI 6.69 to 6.76) based on 21, 83, 877 confirmed and 1,46,872 death cases(as on 17th April,2020). Belgium was highest CFR 13.95% as compared to others. However, India’s CFR was found to be around 3.26% (as on 17th April, 2020). Conclusion: In conclusion, the estimation and interpretation of CFR is critical in response to ongoing COVID-19. The initial CFR estimates are subject to change, still it is useful for healthcare planning over the coming months. Moreover, the precise and robust estimates of CFR will be available only at the end of the epidemic.


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